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Wednesday, January 20, 2016

Bryony Graham: another scientist who writes about the junk DNA controversy without doing her homework

I was searching for information about Craig Venter and his position on junk DNA when I stumbled upon this post by Bryony Graham: Why we still don’t have personalised medicine, 15 years after sequencing the human genome. She is a postdoc in Molecular Genetics at the University of Oxford so the subject is within her area of expertise.1

The post is from Dec. 1, 2015—that's only one month ago so she should be aware of all the facts concerning junk DNA.

If you are going to write about a subject in your area of expertise then it's reasonable to make yourself informed, especially if you know that the subject is controversial. For some strange reason, this common sense approach seems to be ignored when discussing genomes, evolution, and junk DNA. I don't know why some researchers think they know enough about a subject when all they've done (apparently) is read a few popular press reports.

Let's look at what Bryony Graham (@byrony_g) writes to see whether she is behaving like a proper scientist should behave when writing for the general public. It's worth noting that she was on the shortlist for the 2011 Max Perutz Science Writing Award so somebody must think she's a good science writer.
Not all junk DNA is rubbish

It’s because, over a decade after the first draft of the human genome was published, we still really don’t have any idea of what most of it actually does.
Actually we DO have a pretty good idea about most of our genome. Thousands of papers on transposons and transposon-related sequences have been published. We know for a fact that about 50% of our genome consists of bits and pieces of defective transposons derived from once active transposons. We know quite a bit about the rate of decay and quite a bit about the transposons that are still active.

We know where transposons sequences come from (SINES and LINES) and we have a good theoretical understanding of why the bits and piece are still in our genome in spite of the fact that they have no function.

There are thousand of papers on introns. They make up about 25% of our genome. We know about their evolution and we know about their sequence conservation, or lack of conservation. We know how introns are spliced out and what sequences are required for that function. We have very good reasons for concluding that the vast majority of intron sequences are unnecessary for a functional gene.

There are thousands of papers on highly repetitive DNA. This includes centromeric regions and telomeres. We know a lot about such sequences and which ones are important.

We know about protein-coding genes and we know about genes for functional RNAs. We know about origins of replication and scaffold attachment regions. We know about regulatory sequences and how much DNA is required for regulation. We know that less than 10% of the human genome sequence is conserved. We know about other genomes and the "C-Value Paradox."

In other words, 15 years after the announcement of the human genome sequence we have a damn good idea about what most of it actually does. It's mostly junk.
One of the most surprising outcomes of the completion of the first draft of the sequence was that there are far fewer genes than anyone anticipated. In fact, genes make up only 2% of the human genome, with the remaining 98% often dismissed as “junk” DNA.
It's a myth that knowledgeable scientists2 were surprised to find "only" 30,000 genes in the initial draft sequence.
Genetic load arguments alone yielded an estimate of fewer that 30,000 genes back in the late 1960s. Knowledge of the genes in Drosophila, C. elegans, and yeast led to very accurate estimate of the probable number of genes in humans. Besides, before the draft sequence of the human genome was published we already had the sequence of chromosome 22 (1999) and an extended regions of the MHC locus (1991). Extrapolating from those regions gave estimates of 20,000 - 30,000 genes in the entire genome.

Knowledgeable scientists were very happy when the human genome sequence was published because their predictions turned out to be accurate.

As for the idea that all noncoding DNA was dismissed as junk, this is also a myth. No knowledgeable scientist ever claimed that all noncoding DNA was junk, even 45 years ago. Such scientists would have to have been completely ignorant of genes for functional RNAs, regulatory regions, origins of replication, and centromeres to name just a few of the noncoding functional DNA sequences that were known back then.

It doesn't take much effort to discover that this is a myth. A simple Google search will reveal the truth. But even that shouldn't be necessary. All you have to do is discuss this claim with your colleagues, mentors, and students and pretty soon someone will correct you (I hope). You would think that most scientists in the field would have had such discussions before writing about junk DNA for the general public.
The next surprise came when, after sequencing the genomes of thousands of patients suffering from a variety of genetic disorders, scientists discovered that 88% of changes to the genetic code that correlated with the disease were found in the junk DNA.
This statement may be true. It's possible that the experts on genetic diseases were unaware of the importance of regulatory sequences in controlling gene expression. They may have been surprised.

What's not true is that 88% of the mutations causing genetic diseases were found in junk DNA. Many of them are in promoters and enhancers that were never counted as junk. Some of them occur in true junk DNA regions where a new splice site or a new promoter/enhancer is created by mutation. Those regions are still junk DNA. (It's also not true that they are changes in the "genetic code" but that's quibbling.)
The Wellcome Trust has just awarded a £3m grant to the institute where I work, the MRC Weatherall Institute of Molecular Medicine at the University of Oxford, to process samples of DNA from patients known to have a given genetic disease, identify the changes to the DNA which underlie the condition in question, and try and link these changes to genes which may cause the diseases themselves.

With this strategy, we hope to add functionality to the DNA sequence information, and try to work out what that 98% of junk DNA actually does and how it contributes to disease progression.
I think we have a pretty good idea what we're going to find when we identify the mutations that cause genetic diseases. I'm very confident that it won't change the fact that 90% of our genome is junk.

The important question here is how did we ever get into a situation where so much misinformation is accepted by people who are supposed to be experts in this field? And how did we get into a situation where healthy skepticism is not a prerequisite to writing about science for the general public?

It seems to be younger scientists who won't take the time to inform themselves about the scientific literature before expressing an opinion on a controversial topic. Why has this become acceptable?


1. Here's what she says on her profile: "My research interests focus on understanding the non-protein coding regions of the genome, or 'junk DNA', using stem cells and red blood cells as experimental systems.

I feel very strongly that effective communication of scientific concepts to non-scientific audiences is critical to research process; providing those involved in policy, education and media with accurate and up-to-date information is essential to achieving maximal impact of scientific research."

2. The only ones who count in such a discussion.

156 comments :

Aceofspades said...

I think it's pretty clear from her continued distinguishing of the 2% from the 98% that she thinks everything apart from exons was at one point labelled "junk".

*facepalm*

judmarc said...

It seems to be younger scientists who won't take the time to inform themselves about the scientific literature before expressing an opinion on a controversial topic.

I'm guessing without much difficulty you might find examples of older scientists with the same behavior.

What I'd love to see is a substantive discussion of the topic with Dr. Graham here on your blog, if she'd agree to do so, in order to get her views after having read your post.

Aceofspades said...

It's a shame we don't see more of that. I've never seen a junk DNA denier attempt to address the evidence.

I suspect that this it's mostly due to ignorance of the evidence and ignorance of the definition of the term "junk DNA"

Unknown said...

I tracked down the paper from which she obtained the 88% quote and it is a meta-study of GWAS studies: "Potential etiologic and functional implications of genome-wide association loci for human diseases and traits." In the abstract it states, "Although 88% of TASs were intronic (45%) or intergenic (43%), TASs." (trait/disease-associated SNPs) were not overrepresented in introns and were significantly depleted in intergenic regions [OR = 0.44 (0.34−0.58), p = 2.0 × 10−9]."

I would also refer readers to table S3 in this paper, which shows the log-odds ratio that variants in given regions are associated (emphasis on associated) with disease. In the discussion section of this paper the authors, in my opinion, make a desperate appeal to the importance of non-coding regions in disease; stating "In addition, TAS blocks are significantly enriched in nonsynonymous sites (especially for potentially deleterious sites) and in promoter regions and are depleted in intergenic regions. Despite this enrichment, 43% of reported TASs were intergenic and 45% were intronic, suggesting a greater than anticipated role for noncoding SNPs in common diseases." but these statements are not statistically supported by the evidence in their own paper.

Finally, it should be pointed out that these studies are only looking at associations with diseases. It very likely identified variants are simply in linkage with the true causative variant, or that the particular disease being studied does not have a clearly defined genetic component (refer to table S2 for a list of diseases covered).

It should be kept in mind that many non-functional genetic elements can cause disease. Transposable elements are a nice example of this.

Aceofspades said...

Don't TEs only cause disease when they interrupt functional sequences? How could they cause disease otherwise? Is it through some sort of RNA interference?

Unknown said...

Yes, you are generally correct: TE's generally cause disease by inserting into, or removing functional DNA. There are many other mechanisms (if it is possible, it has probably happened at least once, right?), but disrupting or removing "functional" DNA is the primary mechanism.

Georgi Marinov said...

It seems to be younger scientists who won't take the time to inform themselves about the scientific literature before expressing an opinion on a controversial topic. Why has this become acceptable?

As I've noted in previous threads, it is not necessarily the fault of young scientists alone. Combine a dysfunctional high school education with even more dysfunctional undergraduate education (in large part because faculty are judged by their research performance so they have less and less time to teach the more competitive the research environment becomes) with an often nonexistent graduate education (at least in the biomedical sciences), then compound that with the aforementioned pathologically competitive research environment that selects for people who can produced hot papers on one subject but is mostly blind to the breadth of one's knowledge, and it's not hard to see why we end up where we are. But young scientists are forced to play the game under these rules, they did not set them, so it's not fair to place all the responsibility on them.

Larry Moran said...

But young scientists are forced to play the game under these rules, they did not set them, so it's not fair to place all the responsibility on them.

Nobody forced Nelson Lau or Bryony Graham to write posts or respond to questions from a university PR person. They could easily have refrained from doing that because they don't know enough about the subject to have an informed opinion.

Georgi Marinov said...

We're talking past each other.

I am describing the systemic factors that enable people to be in the positions they are and to do certain things they should not be doing in those positions.

You are taking it as me defending their actions. But I am not.

You are asking why assistant professors are ignorant of fundamental concepts in their own fields, and this is what I addressed. No reasonable analysis of the situation can omit the fact that if anyone has the power to change it, and if anyone contributed substantially to creating the current system, it is people from your generation, not theirs.

SPARC said...

I am afraid that if you visit any molecular biology lab the majority of PhD students and postdocs would not even know not enough but would rather be completely ignorant about the subject. Only to a degree it's their fault. The main problem is that molecular biology has been degraded to some auxiliary technology driven science that has to fulfill medical purposes.

Unknown said...

Dear all,

First and foremost, let me thank you for critiquing my article in such detail; your attention is a compliment, and presumably your participation in this discussion means that you, too, are eager to engage in dialogue and debate.

However, I feel there has been a slight misunderstanding as to the objective of this article. I was tasked with offering an opinion on why the much-heralded promise of personalised medicine that followed the publication of the human genome sequence has yet to be fulfilled. This is not a discussion of whether junk DNA does or does not exist. It is a statement that if I sequence the genomes of thousands of patients and discover a mutation that correlates with the incidence of their disease, it is more likely to fall in a non-protein coding region of the genome than a gene.

I COULD have gone into details about transposable elements, enhancers, CTCF sites, repetitive regions, splice sites, polyadenylation signals, and I COULD have redirected them to Supplementary Table 3 in the ENCODE paper - but quite frankly I think that would have proven rather unappealing to the target audience for this article, who are predominantly non-scientifically trained, and would therefore also have also somewhat have missed the point.

Of course we know a huge amount about the genome and how it works; but this doesn't mean that if we find a SNP that correlates with a given disease, we can therefore immediately understand the precise mechanism by which it causes the disease symptoms. And therefore this adds no value to the treatment regime for the patient in question - and this is why, despite having the ability to sequence the genome, we do not yet have personalised medicine. And this, I reiterate, was the point I was aiming to get across in this article: not a discussion of whether junk DNA exists.

The term itself is of course controversial, and my use of it was intentional: it is a hook, and for a non-scientific audience it works to get them to read an article which would, loaded with hardcore molecular biology, not been top of their bedtime reading list. I personally do not regard its use in this context as inaccurate, but if others beg to differ, you are entitled to your view.

Also, as we seem to have digressed into putting the blame for my apparent ignorance at the feet of either my youthful innocence or my seniors, I would like to point out that this article was read by two professors and also the Director of the institute where I work, who also happens to be the lead author on the £3m grant which I mention. Of course I would not presume that my meagre eight years in academia would warrant my voice as an authority on the subject. But I do hold the opinion of my three mentors with a collective experience of over 90 years in the field as a fairly good indication that I'm not too far wide of the mark.

With respect,

Bryony

Aceofspades said...

Bryony are you aware of the evidence for junk DNA? This paper provides a good summary of that evidence:

http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004351

Can I ask what you think of it?

By the way, I don't agree that it's ever a good idea to misappropriate terms in order to provide a hook to get people interested in science. You're only misleading people and this ultimately does more harm to your cause as a science communicator than good.

Georgi Marinov said...

The term itself is of course controversial, and my use of it was intentional: it is a hook, and for a non-scientific audience it works to get them to read an article which would, loaded with hardcore molecular biology, not been top of their bedtime reading list. I personally do not regard its use in this context as inaccurate, but if others beg to differ, you are entitled to your view.

The right word to describe that attitude is "irresponsible".

Also, situations like this are precisely why it is so devastating for science to be raising generation after generation of lab rats (rather than what the letters "PhD" once stood for) who know nothing about the world around them outside their narrow area of expertise.

The debate around junk DNA has so may and so deep ramifications on so many levels, which, judging by your posts on the topic, it is clear that you do not understand in the slightest. And perpetuating the misunderstanding that junk DNA is bunk is going to hurt science in the long run very badly (which may one day come to bit you personally too). But to understand that, you need to know the subject, its history and the wider societal, cultural and historical context the "controversy" is embedded in.

Unknown said...

I feel as though we are getting further from the original misunderstanding: my article is not a discussion on whether junk DNA does or does not exist. It is a question of whether we know enough about precisely what each mutation that falls anywhere in the genome does to give us enough information to develop personalised medical treatments. Which, despite our ever-increasing knowledge, I do not believe that we do.

The term is indeed controversial but I stand by the fact that in this context, I don't believe that its use is either inappropriate or misleading. It is clearly a starting point for debate, which in my view is absolutely fine. Fair enough to note that it has become somewhat of a cliche, and one which is loved by journalists and hated by scientists (as acknowledged in the PLoS Genetics article) but personally I think the bottom line is that there are so very few detailed functional studies of specific regions of the genome that the topic remains open. An article such as mine which aims to get one idea across to a non-scientifically trained audience is not going to go into a debate on the historical and societal context of whether or not junk DNA exists, interesting as these conversations are.

Larry Moran said...

Bryony,

Thanks for responding. You say,

I would like to point out that this article was read by two professors and also the Director of the institute where I work, who also happens to be the lead author on the £3m grant which I mention.

This is disappointing because the clear take-home message of your article was that disease association studies are showing us that 98% of our genome is not junk but may have a function. This is not correct.

You could just as easily have said the following.

"The best evidence from work done over the past 50 years shows us that only 10% of our genome has a function and 90% is probably junk. Annotated genes make up only 2% of the total so there is 4 times and much functional DNA as the total found in genes.

Many disease causing mutations occur in this functional part of the genome outside of genes, often in regulatory sequence that control gene expression. Some disease causing mutations occur in the junk DNA component where they cause problems by accidentally creating new regulatory sequences that disrupt normal gene expression."

This would be a much more accurate description of reality.

Let me ask you a direct question. In your opinion, how much of our genome is junk? Can you ask the three scientists who read your article before publication? It sure sounds to me like you don't believe in junk DNA but you aren't familiar with the scientific literature on the subject.

Larry

Unknown said...

Hi Bryony,

When commenting on the internet it is easy to forget that there are real people with emotions who might be affected by what you say. I have experienced this before (see the ortholog conjecture paper), and I can understand being defensive.

One thing to point out about this blog is that Dr. Moran probably spends most of his time arguing with creationists. Such individuals often latch onto any claims against the existence of Junk DNA as evidence in support of their viewpoints (God intelligently designed our genomes). Consequently, those arguing against creationism are (rightly) rather quick to dispel any arguments against the concept of Junk DNA. What you may have viewed as an "inert" hook to draw people in, is part of a much larger philosophical and scientific argument.

That being said, I agree; non-coding regions are important when trying to track down variants causing disease. Are they more important than non-synonymous variants (or larger scale deletions and insertions that affect large amounts of DNA)? Probably not, but that doesn't mean they should be ignored.

~Wyatt

p.s. everyone makes mistakes. Dr. Moran tried to argue with me one that the contribution of gene duplication to the creation of new genes is a "baseless" assertion before going on to write a post that illustrates just that.

Larry Moran said...

Bryony says,

... but this doesn't mean that if we find a SNP that correlates with a given disease, we can therefore immediately understand the precise mechanism by which it causes the disease symptoms.

You do realize, I hope, that the association of a SNP with a disease does not tell you a thing about the mutation that causes the disease? The single nucleotide polymorphism (SNP) used to map the disease locus will usually be a neutral mutation in a non-functional part of the genome. It just indicates that the disease-causing mutation is nearby.

It's very unlikely that a single nucleotide polymorphism (SNP) is going to reduce fitness by causing a genetic disease.

Larry Moran said...

... my article is not a discussion on whether junk DNA does or does not exist.

Yes it is. You may regret writing such an article but it's rather disingenuous to pretend that you didn't mean to question the existence of junk DNA.

Larry Moran said...

Here's what you said in your article.

With this strategy, we hope to add functionality to the DNA sequence information, and try to work out what that 98% of junk DNA actually does and how it contributes to disease progression.

Your message is clear. You are telling your audience that some scientists believe that all noncoding DNA is junk—this is false—and you hope to prove that it is not junk.

Beau Stoddard said...

Aside from arguing with Theists, why is the junk DNA topic so hot? How is it harmful to search for purpose in what has been labeled junk? I guess i don't understand the end game here.

Faizal Ali said...

The problem is scientists who purport to educate the general public, but who mislead them instead.

Anonymous said...

"They could easily have refrained from doing that because they don't know enough about the subject to have an informed opinion."

But they'd have to know enough about the subject to know that they didn't know enough about it to have an informed position. And they don't. It seems to me that people who don't understand junk DNA are the most likely to write about it.

Anonymous said...

Dr. Graham, On the one hand, I admire your ability to firmly and politely hold to what you think is true, and to explain your position. This will be valuable throughout your life.

On the other hand, you're wrong about junk DNA. I know I'm saying that as a pedantic botanist, but precise word choice matters, for its own sake, independent of its role in culture wars. (I'm sure you value precision highly in the parts of your studies that matter to you.)

Junk DNA does not mean all non-coding DNA. Never did (within genetics). Wouldn't make sense if it did; could it possibly make sense to call promotors junk DNA?

Non-junk DNA includes protein-coding regions, regions coding for useful RNA's, telomeres, centromeres, important structural elements, etc. Junk DNA is the rest, that stuff that (as far as we know) doesn't have any important function.

By misusing the term junk DNA, you've drawn attention away from the important part of your paper, the find that some sequences linked to diseases occur in actual junk DNA. (As Dr. Moran stated, that's probably a result of linkage rather than actual disease causation, but still, it's interesting information.)

I'm pretty sure you'll be a master of junk DNA by the end of the week. Dr. Moran's posts on the topic on Sandwalk are not a bad place to start looking for useful information.

BC said...

Generally, junk DNA is used as a straw-man argument against creationists. Contrary to what you might read here, the amount doesn't matter (even if very high, we might expect that in our fallen state).

However, for evolutionists a high percentage of non-coding DNA is vital. If this is not the case then the mutational load would be too great (we couldn't have evolved because we'd be extinct). The 'knowledgable scientists' know this, and that's the reason junk DNA is a hot-topic.

AnotherYoungScientist said...

The problem is that "proper" scientists should know that, similar to research, in writing, the article depends on the question one is asking.

The question for this article revolved around personalised medicine, and how close/far we are from attaining "precision/ precision medicine". It was not planning to clarify the existence of junk DNA, or to explain the entire philosophical arguments from debates with creationists.

For the general public, we should maybe keep in mind that the more practical aspects matter- do we know enough to cure disease? No. The most experienced in the field, that is in the field of genetics and genomics, admit we don't.

How is the article misleading? Because the public is not faced with an explanation of transposons/ introns / whatever topic we prefer from the non-coding genome? Or presented with the fact that the scientific community does not agree on definitions?

The article had a topic- it was not meant to be an encyclopedia. By all means, contribute to the public engagement efforts and write articles about all of these other aspects.


However, most of the so-called arguments in Mr Moran's post and comments revolve around more or less attacking the writer of the article, with whom he disagrees. The proper scientists he refers to, should be able to argue without generalisations based on aspects such as the age of the scientist. It is a controversial topic, which requires debate from multiple viewpoints. However, the patronising, scolding tone should have no place in such a discussion.

When did it become acceptable to attack personal sphere, rather than have an objective scientific debate on the topic?

Dave Carlson said...

Even accepting that the topic of the article is personalized medicine and not junk DNA, parts of it are quite problematic. Take the following:

"With this strategy, we hope to add functionality to the DNA sequence information, and try to work out what that 98% of junk DNA actually does and how it contributes to disease progression."

The implication here is that people believe that the 98% of DNA that doesn't code for proteins is all junk. Perhaps there are folks that think so, but that certainly isn't the consensus among those who think that most of the human genome is composed of non-functional sequences.

Unknown said...

Do these "personal sphere" complaints ever get levied by the side who is winning the argument?

Gary Gaulin said...

BC noted: Contrary to what you might read here, the amount doesn't matter (even if very high, we might expect that in our fallen state).

Excellent observation BC! That might help explain why (other than a few exceptions) junk-DNA is otherwise a religious non-issue.

Anonymous said...

I agree that the article in question had no obligation to explain junk DNA. It just had an obligation to gets the bits on junk DNA right (if the term "junk DNA" was to be included at all).

Petrushka said...

Perhaps an attack on the writer is in order. It's not a personal attack. It's an attack on professional output.

If you do sloppy lab work, you will probably be held personally accountable. So why not be accountable for sloppy writing.

This kind of stuff gets quote mined for decades by creationists.

gnomon said...

Larry: "It seems to be younger scientists who won't take the time to inform themselves about the scientific literature before expressing an opinion on a controversial topic. Why has this become acceptable?"

It seems what you said fits yourself the best. The junk DNA notion is all based on misguided wishful assumptions (not facts) if you care to find out about its origins. Your knowledge of it is at least 20 years behind the cutting edge and you have zero track record in the relevant field in the first place. You should first catch up with the latest literature, including a dozen peer-reviewed papers from my group in the last 7 years. If my papers have yet to be widely appreciated, which you may use as a convenient excuse for being blind to them, at least you should know that the field has a major century old and widely acknowledged unsolved-mystery of what determines genetic diversity, to which the junk DNA concept is directly relevant. On that note alone, one can conclude that the junk DNA is at least a useless notion if not outright false. (Our recent papers have in fact shown that it is false by using real experimental data.) You are not setting a good example for young researchers by cherry-picking research and by voicing strong opinions on topics you have no first hand research experience.

Aceofspades said...

@Beau
I'm all for searching for purpose in non-coding DNA. The point is: while we know how much of it is ultimately functional based on things like genetic load and sequence conservation, we still need to locate all those sequences which lie within that functional domain. This is a worthwhile pursuit.

This is important because the concept of junk DNA and neutral sequences are essential to population genetics. If you write those off, you write off an entire field of study that has made and confirmed many predictions.

SRM said...

Generally, junk DNA is used as a straw-man argument against creationists. Contrary to what you might read here, the amount doesn't matter (even if very high, we might expect that in our fallen state).

So true. And let us not forget the tribes of Allium who have lived like the lowest beings amongst dirt and filth like so many snakes and pigs. And for them, nary a saviour Leek came forward to be sacrificed upon a fiery spit and then ascend to heaven, so as to pay for the sins of the fallen onions and garlics, and such.

Aceofspades said...

It's really not good enough to mislead the public just because statements are attention grabbing or controversial.

What do you think it does for public perception of science when the newspapers report one thing one day:

- Just 8.2 per cent of our DNA is ‘functional’ (link)

- Human Genome Is Mostly 'Junk DNA,' With Only 8.2% Functional (link)

- Less than 10% of human DNA has functional role, claim scientists (link)

All articles above based on this study

And then "science communicators" come along and clearly not understanding the topic, claim that everything non-coding is junk by telling people that we once thought 98% of the genome was junk?

Confusing and misleading people is exactly the opposite of what science communicators should be doing.

Faizal Ali said...

If absence of junk DNA is not an essential creationist argument, you should inform the Intelligent Design creationists, who are constantly using it as one. (With a few exceptions, like VJ Torley.)

Junk DNA as an anti-creationist argument only arises in reaction to when denial of junk DNA is used as a creationist one.

The Lorax said...

Zzzzzz

Unknown said...

Could you post some links? I need a laugh, I mean stay informed on the pertinent literature.

ET said...

I read this article, and I'm disappointed - well almost disgusted... not at Dr Graham's science, but at the way in which you felt it reasonable to personalize the whole issue.

You are behaving in a manner that is typical of your generation and gender, and help maintain the stereotype of the arrogant, almost untouchable male scientist.

Spare a thought for your victims, whether Massimo Pigliucci, Bryony Graham or Nelson Lau, and ask whether the personalization of their research particularly when trying to achieve greater public understanding is really appropriate or even professional for someone in your position.

Discussion yes; personalized attacks no.

I look forward to notices of the retirements of your generation, knowing that scientific research funding is going to those who know that nurturing the new generation is more important than preserving their own pedestal.

You want to work with good young scientists? Treat them with more respect; educate and nurture, don't bully.




Faizal Ali said...

Jeez, ET. You insult Larry on the basis of his age and gender and then try to make a plea for civility? At least try to be consistent.

Mikkel Rumraket Rasmussen said...

"Spare a thought for your victims, whether Massimo Pigliucci, Bryony Graham or Nelson Lau, and ask whether the personalization of their research particularly when trying to achieve greater public understanding is really appropriate or even professional for someone in your position."

What utter nonsense! Greater public understanding isn't achieved by pussy-footing around people who are demonstrably, unambigously wrong and should simply know better.

There's nothing overly personalized about anything Larry has written, rather the issue seems to be the propensity for the "afflicted" to take mere correction as a personal attack on their character and worth in the first place. Which they should simply stop doing, look at the controversy about the science more in-depth, and then accept the correction and move on.

Being corrected isn't bullying, I was bullied at school so give me a break. I've also been corrected, often, so I know the difference very well.

Chris B said...

Actually, BC, you have it exactly backwards. Geneticists and scientists in general have no vested interest whatsoever in what proportion of our genome is junk. It is another part of genomic knowledge to be learned, and the answer itself will have no real affect on "evolutionists".

Conversely, ID/creationists have latched onto this controversy because they desperately want to find signs of intelligent design in our genome, for which they currently have zero evidence. It matter to them, not to scientists, who just want to know the real answer.

Fair Witness said...

gnomon - Please post links to your papers. I would like to read them.

Anonymous said...

The pattern I've noticed is that people who are unconcerned about creationist influence in the US and Australia tend to be sloppy in their discussions of 'junk DNA'. I think these people see the growing list of new layers of regulation and regulatory regions in unexpected places such as TEs and extrapolate wildly to conclude that most of the DNA is functional. Perhaps they also use a more loosely defined definition of function that includes things that don't have sequence dependence and can be deleted without effect. This is all worthy of discussion and may be justified but right now the evidence clearly indicates 10-15% function at the most and this is what should be reported to the public. I understand BG wanting to use junk DNA as a 'hook' to lure people in. But she didn't need to misinform them within the article, she could have either not mentioned it at all or used it as an opportunity to clear up misinformation on the topic.
Creating personalized medicine means cataloging all of the variants that contribute to disease in different individuals and then tailoring a treatment to each individual depending on their variants. Explaining this does not required a discussion on junk DNA much less misinformation on the topic.
I think Moran was overly harsh in his criticism but perhaps this is the only way to get people to put some thought into what they write for the public

Faizal Ali said...

No, you wouldn't. You have been warned.

Aceofspades said...

Shi Huang, could you explain to me why you think the modern synthesis cannot account for the genetic equidistance phenomenon? And then how you think your "maximum genetic diversity hypothesis" resolves this?

I looked up this recent paper of yours and after reading the abstract, I have immediate concerns about the potential for bias and motivated reasoning here.

Statements like this:

> Molecular interpretation using MGD-based methods reveal novel insights on the origins of humans and other primates that are consistent with fossil evidence and common sense, and re-established the important role of China in the evolution of humans

and this:

> The idea of limit or optimum is in line with the yin-yang paradigm in the traditional Chinese view of the universal creative law in nature

immediately alert me that you may have preferred beliefs or ideologies that you are attempting to find evidence to support.

Aceofspades said...

I don't think the biggest issue here is creationism

Junk DNA is really important for neutral theory which in turn is hugely important in population genetics and we all know what Michael Lynch had to say about the importance of population genetics.

You can't just undermine something as foundational to evolution as this (without an extremely string case to present) and then not expect a strongly worded response from professors the world over.

gnomon said...

No. I am motivated only by solving mysteries. I could care less about any belief systems that are useless. The junk DNA and modern synthesis have some values in microevolution but are largely useless for major mysteries.

The following from one of my earlier papers:
This explanation of the genetic equidistance result by the MGD hypothesis can also be easily illustrated by a simple thought experiment. If we can create a yeast, a fish, and a human being by using identical genes for their shared homologs and let the three organisms diverge for an infinite amount of time or about 500 million years, a gene in yeast would have changed a lot to a maximum of, say 50%, while its homolog in fish would have changed to a maximum of, say, 30%, and its homolog in human would have changed very little, say less than 1%. Any more changes than 50% would be lethal to yeast; any more changes than 30% would be lethal to fishes; and any more changes than 1% would be lethal to humans. The reason that a gene in yeast can change much more than in fish, which is still more than in human, is because a gene in human encounters far more functional constraints than its homolog in fish or in yeast. Thus the genetic distance between yeast and human or fish is mainly determined by the mutations in yeast. In this case, the 50% change in yeast would account for the genetic distance of 50% identity between yeast and human or between yeast and fish, as well as 50% identity in within species distance in yeast. The 30% change in fish would account for the genetic distance of 30% identity between fish and human. In contrast, the modern evolution theory would predict that both human and fish can also, like yeast, change up to 50% and would have a genetic distance of 50% identity.

judmarc said...

Dr. Graham:

First, thank you for participating in the discussion. Much appreciated.

As a non-scientist keenly interested in many of the topics discussed on this blog and touched on by your research, I think I'm probably part of the target audience that was being sought with the use of the term "junk DNA."

My reaction to your explanation is that I'm disappointed. No, not play-the-sentimental-violin-for-me disappointed, and not you-haven't-met-my-expectations-as-a-human-being disappointed. This: I love science because I want to *know*. If I want fairy tales for people who can't grasp reality, I know where to look for them in the library or online. I want to know about atomic orbitals and electron configurations, and you're giving me valence theory.

Even - perhaps especially - when communicating with the lay public, please do us the favor of being precise and accurate. Specifically with regard to this topic, be scrupulous about the difference between non-coding and junk DNA. We'll thank you for it.

gnomon said...

Fair Witness,

please go to my lab website for links to pdf downloads of all my papers in the last 8 years, Shi Huang Lab

For the latest review of our work, go to this preprint currently under review, New thoughts on an old riddle: what determines genetic diversity

A list of papers published within last year alone, just to illustrate the power of a no-junk perspective, i.e., the MGD theory, in solving major biomedical problems. Last time I checked, Kimura, Ohta, Nei, Lynch, Ayala, Felsenstein, all of whom major figures in the neutral camps, have published zero papers in using the neutral or junk DNA model to solve real life human disease problems. In science, a useless model is evidence of falsehood.

68. Zhu, Z., Man, X., Huang, Y., Xia, M., Yuan, D., and Huang, S. (2015) Collective effects of SNPs on transgenerational inheritance in Caenorhabditis elegans and budding yeast. Genomics, 106: 23-29. http://dx.doi.org/10.1016/j.ygeno.2015.04.002

69. Zhu, Z., Yuan, D., Luo, D., Lu X., and Huang, S. (2015) Enrichment of minor alleles of common SNPs and improved risk prediction for Parkinson's disease. PLoS One, DOI: 10.1371/journal.pone.0133421

70. Zhu, Z., Lu, Q., Wang, J., and Huang, S. (2015) Collective effects of common SNPs in foraging decisions in Caenorhabditis elegans and an integrative method of identification of candidate genes. Sci. Rep. 5, 16904; doi: 10.1038/srep16904

71. Zhu, Z., Lu, Q., Zeng, F., Wang, J., and Huang, S. (2015) Compatibility between mitochondrial and nuclear genomes correlates with the quantitative trait of lifespan in Caenorhabditis elegans. Sci. Rep. 5, 17303; doi: 10.1038/srep17303.

73. Luo, D., and Huang, S. (2015) The genetic equidistance phenomenon at the proteomic level. bioRxiv, doi: http://dx.doi.org/10.1101/031914

74. Huang, S. (2015) New thoughts on an old riddle: what determines genetic diversity within and between species. arXiv:1510.05918

Anonymous said...

The 2 are related but I don't think the proportion of junk DNA in the genome is directly related to neutral theory. Neutral theory would be valid whatever the proportion. After all, you can neutral mutations withincoding sequences

Georgi Marinov said...

@ Aceofspades

Actually, that most of the genome should be junk would still follow from the data even if all species were specially created 6000 years ago.

It is a necessary conclusions based on the size of the genome and the empirically measured (countless times) mutation rate.

So if you are a young earth creationist, your best option is to either dispense with the notion that "god makes no junk" (an omnipotent God could presumably do whatever he wants to, clever philosophical paradoxes that don't apply to this case aside) or to go with the "this is a consequence of the Fall" craziness (which would be once again a case of creationists believing in orders of magnitude more evolution than scientists are willing to accept). The latter, ironically, would not be that far off from the truth, it just gets the timing wrong by about 5 orders of magnitude -- we were perfectly happy highly adapted streamlined prokaryotes floating around in the anoxic Archean ocean but then we "decided" to evolve photosynthesis, nearly killing ourselves and freezing the whole planet to death in the process, then to become eukaryotes and later to evolve multicellularity, the end result of which was filling ourselves with unjustified pride of our complexity and phylogenetic greatness while in fact greatly reducing our long-term evolutionary fitness and filling up our genomes with junk :)

Aceofspades said...

@Georgi

Please don't insult me. What could possibly make you think I'm a creationist? I have no idea how you could have read my comment and come away with that idea. I am arguing for the existence of junk DNA - Creationists annoy me too, I just happen to think that the bigger issue at stake here is population genetics

Georgi Marinov said...

???????

TheOtherJim said...

http://journal.sjdm.org/15/15923a/jdm15923a.pdf

Arlin said...

This is a manufactured controversy. The main problem is not that Graham is mistakenly rejecting the idea of junk DNA, but simply that she is not using the term correctly. She clearly thinks it is synonymous with "non-coding DNA". This is utterly obvious when she says things like "It is known that one thing harboured in this junk DNA are switches that tell certain genes when and where in the body to turn on". Whe ends with talking about a project and concludes "With this strategy, we hope to add functionality to the DNA sequence information, and try to work out what that 98% of junk DNA actually does and how it contributes to disease progression."

This just doesn't say that there is no junk. Graham is right. This article is not fundamentally about junk DNA. Yes, we all have a responsibility to be accurate and not use "junk DNA" to mean "non-coding DNA", but this doesn't distort the issues presented in the article. Just substitute "non-coding DNA" and the article is perfectly sensible.

DGA said...

Aceofspades, I think Georgi was using "So if you are a young earth creationist" in the sense of "So if one is a young earth creationist". I think he did not actually mean you personally.

Aceofspades said...

Oh shit... Maybe it's me with the reading comprehension problem?

Unknown said...

Arlin says, "she clearly thinks it (junk DNA) is synonymous with non-coding DNA." That is precisely the problem, and it definitely distorts the picture of what is functional in the genome and what these studies tell us about disease. You do realize when people say "functional DNA" they are also referring to non-coding DNA??? Again, it's been said several times in this thread, a SNP associated with a disease does not make that SNP functional.

Since you're not grasping the topic at hand, it makes me think this has more to do with Larry's tone.

BC said...

Sorry Chris, but you are wrong. You should read Professor Moran's blog post entitled 'Genetic Load, Neutral Theory, and Junk DNA'.

TheOtherJim said...

Did anyone see the slightly related Allium "comment" on the topic?

Faizal Ali said...

Did you happen to read the last paragraph of that article, BC?

BC said...

Yes lutesuite. Did you happen to read the first paragraph of my first comment in this thread?

Scott Draper said...

As a layman, I've been repeatedly baffled over the years about the status of junk DNA, with many articles purporting to undermine its existence. This post and comment thread has, for the first time, given me clarity on the issue.

However, if I had read Graham's article, I would have come away confused again. So while I wince when I imagine myself to be the target of such a critique, I'm relieved to know that my confusion isn't totally my fault.

Chris B said...

Sorry, BD, but you have it bass ackwards again. The article you directed me to proves my point. The genetic load idea is based on empirical data, experimentally determined mutation rates. Scientists form their ideas about what fraction of our genome is nonfunctional based on facts. Unlike ID/creationists they do not try to shoehorn reality into their preconceived religious beliefs.

Dr Moran sums up the ID/creationist position:
"Creationists will never understand this because: (a) they believe that modern evolutionary theory is all about "Darwinism" and Darwinian evolution doesn't recognize neutral mutations and random genetic drift, and (b) they can't admit to junk DNA because that's the opposite of what intelligent design would look like."

As for your specious claim that ID/creationists are fine with lots of junk DNA because this somehow reflects "the Fall" (another fairy tale for which you have no evidence), this puts you at odds with pretty much all the other ID/creationists. Have a look at what creationist charlatans like Casey Luskin, Jonathan Wells et al. have to say about it.

Chris B said...

Gnomon,

"Any more changes than 50% would be lethal to yeast; any more changes than 30% would be lethal to fishes; and any more changes than 1% would be lethal to humans."

How do you determine the maximum % difference that can be tolerated in different species?

gnomon said...

In an ideal world where the genome of every species has been known, the largest distance between any two species within a clade would be close to the maximum tolerated for that clade. To verify it, that distance should be similar to the distance between a species of that clade and a higher complexity species such as chimpanzee or human. Take cytochrome c as an example, the following are from my 2008 paper.
This notion that the maximum genetic diversity of a simple kind of outgroup organism determines the distance between the outgroup and the more complex clade can be illustrated by the example of cytochrome c. The maximum diversity in this protein sequence is about 70% difference within bacteria, for example, between Bordetella parapertussis and Paracoccus Versutus. The maximum distance between bacteria and mammals is about 65% difference, such as between Bordetella parapertussis and Pan troglodytes (chimpanzees). Within fungi, the maximum diversity is about 40% difference, for example, between Aspergillus oryzae and Yarrowia lipolytica. The maximum distance between fungi and mammals is about 43% difference, such as between Aspergillus oryzae and Pan troglodytes. Within arthropods, the maximum diversity is about 24% difference, for example, between Drosophila melanogaster and Tigriopus californicus. The maximum distance between arthropods and mammals is about 25% difference, such as between Drosophila melanogaster and Pan troglodytes.

Faizal Ali said...

Yes. You obviously don't understand the concept of genetic load, probably because you're an ignorant, stupid creationist (Sorry for being so redundant there).

If there is no junk in the human genome, then how could the human species survive 130 mutations per individual per generation? That question would still arise if humans were magically created by God 10,000 years ago.

Here are a few hundred examples of creationists using the (as they claim) non-existence of junk DNA as evidence for creationism, which you deny they ever do:

http://www.uncommondescent.com/?s=junk+dna

Lies make baby Jesus cry. Didn't you know that?

Faizal Ali said...

(Above post was directed in response to BC.)

Steve said...

Larry is just scratching for blog hits.

Larry does not have a nose for discovery. That's why he teaches and doesnt do research.

Its Lau and Graham that are doing the research and likely have little use for Larry's whining and bitching about his pet peeves.

Smart money is on watching sunrises from lab windows, not sunsets from university balconies.

Anonymous said...

@gnomon

You say:
"The reason that a gene in yeast can change much more than in fish, which is still more than in human, is because a gene in human encounters far more functional constraints than its homolog in fish or in yeast. "

1. Based on what evidence can you say that human genes encounter more functional constraint than it's homolog in fish or yeast?

-Doesn't that massively depend on the gene & the selective pressure? What about duplicate genes?
-Is that true for most genes? (evidence please)
-Is that true for most non coding sequence? (evidence please)

2. Does the 'maximum diversity' (whatever that should tell me) in a clade not depend as well on the age of the clade and the generation time in that clade?

-Are mammals not derived from bacteria? Couldn't that be the explanation for the similar numbers of 'in between difference' for bacteria and 'between difference' for bacteria and mammals?

3. And again:
-What does more complex mean? How do you measure it ? (a reproducible procedure, please)
-Who is more complex: a dog a cat or a squirrel? Who is more complex: a Chinese or a European? Who is more complex: A salamander with a genome size of 100Gb or a salamander with a genome size 20Gb?

Aceofspades said...

To nitpick, she did say she wanted to find functions *for* the other 98% not *in* the other 98%.

In any case, its irrelevant whether she privately thinks 100% of our genome is functional our not. What matters its that she's adding clarity, not confusion in her communication with the public.

Chris B said...

So do phylogenetic trees then reflect the hierarchical order of complexity of organisms rather than their genetic relatedness?

How do you quantify and assign values of 'complexity' to species to do your analyses? How do your determine what a clade is?

How does this concept relate to genome size?

Aceofspades said...

@gnomon, you wrote:

> The reason that a gene in yeast can change much more than in fish, which is still more than in human, is because a gene in human encounters far more functional constraints than its homolog in fish or in yeast. Thus the genetic distance between yeast and human or fish is mainly determined by the mutations in yeast.

How are you determining the amount of functional constraint that genes are subject to? I can see that to a first approximation, an argument could be made for this based on gene count. If yeast has 5,000 genes and humans have 20,000 genes then I guess one could make up some definition for genetic complexity based on this and say that human genes experience 4x as much functional constraint than yeast. But then by this measure puffer fish would be just as complex as humans since they have a similar gene count. So I don't see any argument for claiming that fish could sustain more changes than humans or that yeast could sustain 50x as much change as yeast. Where have you got these numbers from?

Moving now to your later comment. I don't see why the "complexity" of an organism would have anything to do with the amount of change that could be sustained in cytochrome-c. Cyt-C sits on the mitochondrial genome and all of the species you've mentioned have mitochondrial genomes of similar complexity. It stands to reason then that the amount of functional constraint in human cyt-c is similar to the amount of functional constraint in yeast cty-c. Do you believe that Cyt-C has to interact in some functional way with any genes or products from the nuclear genome? Do you have evidence for this?

Aceofspades said...

@Georgi Marinov

I misunderstood your comment and I thought you had assumed me to be a creationist. You wrote:

> Actually, that most of the genome should be junk would still follow from the data even if all species were specially created 6000 years ago. It is a necessary conclusions based on the size of the genome and the empirically measured (countless times) mutation rate.

I agree with what you've written here but I'm not sure how it relates to my comment that I think the greater concern raised by the denial of junk DNA are it's implications for neutral theory and the importance that genetic drift plays in speciation.

@lantog

Codon degeneracy will allow what? At most 20 - 25% of mutations within functional regions to be neutral? Add a few percentage points to that to allow for the fact that some proteins work just as well when they have certain amino acids swapped out and what we are left with is not nearly enough to account for the importance that genetic drift is supposed to play in speciation according to population genetics.

Justin said...

To get a picture of Dr Graham's understanding (or lack thereof), of junk DNA have a look at this blog post, and count the misconceptions:

http://www.imm.ox.ac.uk/not-all-junk-dna-is-rubbish

Mikkel Rumraket Rasmussen said...

Holy crap. She really does believe that all non-coding DNA is thought to be junk-DNA.

Aceofspades said...

That was painful to read.

Bryony mentioned that her work had been read by two professors and also the Director of the institute where she works. It's difficult to make sense of that when we note that researchers at the same university as her produced this paper:

8.2% of the Human Genome Is Constrained: Variation in Rates of Turnover across Functional Element Classes in the Human Lineage

Georgi Marinov said...

Bryony mentioned that her work had been read by two professors and also the Director of the institute where she works.

Since nobody mentioned that, let me be the one who makes the nasty remarks again -- the fact that she brought it up is itself a huge problem. That's the kind of appeal to and reverence for authority that was supposed to not have a place in science, and that has dragged down and almost destroyed many scientific cultures around the world. It was really bad on the other side of the Iron Curtain -- nobody junior dared say something without approval from his superiors -- and I can still observe that in people I have grown up with but who stayed and got their PhDs there. Western science is supposed to have a different culture, where the facts alone and not what anyone says matters, and this has contributed greatly to its success over time. So hearing this from someone at the postdoc level is really worrying.

Sure, have the text reviewed your advisors -- they're your closest collaborators, they can provide useful input, and they might want to make sure you have not said anything embarassing. But to then say "they approved it, it has to be correct" when being criticized... That is just not right :(

Mikkel Rumraket Rasmussen said...

Minor quibble, still annoying: She also incorrectly uses the term "genetic code" to refer to all DNA sequence, rather than the translated sequences, in the article that spurred this thread :P

Justin said...

Irony overload:
https://theconversation.com/profiles/bryony-graham-195605

Joe Felsenstein said...

Indeed. If we say that an English novel, such as David Copperfield is written in an "alphabetic code", is that code the string of letters that is the novel, or just a one-page table showing all of the letters in the English alphabet? Science popularizations sadly often use the term "genetic code" for the former.

Aceofspades said...

At the same time if I was writing a computer program and I was to show you my code, it wouldn't be a table of syntax and possible commands - it would be a document showing the way in which I had arranged those codes.

Mikkel Rumraket Rasmussen said...

Oh for fucks sake.

BC said...

Chris,

Let me remind you of your original claim:

"Geneticists and scientists in general have no vested interest whatsoever in what proportion of our genome is junk."

The article I directed you to does not prove your point, it contradicts it. Perhaps you noticed, because you go on to make a new claim:

"Scientists form their ideas about what fraction of our genome is nonfunctional based on facts. Unlike ID/creationists they do not try to shoehorn reality into their preconceived religious beliefs."

Wrong again. Genetic load is a problem, so the proportion of junk is not "another part of genomic knowledge to be learned". A large percentage of junk DNA is shoehorned in to uphold the belief in evolutionary theory.

"As for your specious claim that ID/creationists are fine with lots of junk DNA because this somehow reflects "the Fall" (another fairy tale for which you have no evidence), this puts you at odds with pretty much all the other ID/creationists. Have a look at what creationist charlatans like Casey Luskin, Jonathan Wells et al. have to say about it."

I've never seen a single creationist claim that our genome has not degraded from its original state (even if we could know what that might look like). Some might argue for low amounts of junk, but whatever the future reveals as the final proportion is a non-issue. This is not the case for evolutionists:

"If ENCODE is right then evolution is wrong."
(Dan Graur)

Which also contradicts your earlier comment that "the answer itself [the final proportion] will have no real affect on evolutionists". It looks like you're the one that's got it "bass ackwards" after all.

BC said...

lutesuite,

"Yes. You obviously don't understand the concept of genetic load, probably because you're an ignorant, stupid creationist (Sorry for being so redundant there)."

You failed to present any evidence that indicates my claim regarding genetic load is incorrect or that I've misunderstood the concept. Probably because you're a dishonest evolutionist.

"If there is no junk in the human genome, then how could the human species survive 130 mutations per individual per generation? That question would still arise if humans were magically created by God 10,000 years ago."

I never claimed "there is no junk in the human genome". You should read what I actually wrote instead of misrepresenting it.

"Here are a few hundred examples of creationists using the (as they claim) non-existence of junk DNA as evidence for creationism, which you deny they ever do: http://www.uncommondescent.com/?s=junk+dna"

Once again you are misrepresenting my claim. The amount of junk DNA matters far more to modern evolutionary theory than it does to creationists (even if some argue for a lower amount).

"Lies make baby Jesus cry. Didn't you know that?"

Oh, the irony.

Mikkel Rumraket Rasmussen said...

"Genetic load is a problem, so the proportion of junk is not "another part of genomic knowledge to be learned". A large percentage of junk DNA is shoehorned in to uphold the belief in evolutionary theory."

No, junk is implied by genetic load. That in itself might not have been enough to really prove there was lots of junk, but then this isn't all there is to the junk-DNA argument either. The genome has been sequenced, we know what most of it is. Introns, defective transposons, pseudogenes and so on. Then there's the fact of it's extremely low expression levels, the lack of sequence conservation, that in studies of mince large swathes can be removed without effect, there's the comparative genome-size variations between different species etc. etc.

Simply put Christ is absolutely right, It's the evidence that overwhelmingly supports the case for lots of junk, not some kind of imagined ideological committment to junk to "save" evolution from genetic load.

"I've never seen a single creationist claim that our genome has not degraded from its original state (even if we could know what that might look like). Some might argue for low amounts of junk, but whatever the future reveals as the final proportion is a non-issue. "

Utterly false, the final proportion is the MAIN issue. The fact that creationists aren't (mostly) so incredibly deluded they still think even the vitamin c pseudogeone is functional (oh, wait!...) isn't a point in their favor. The general idea from creationists is that their god would not design a genome that is MOSTLY junk. For fucks sake, the fact that you people constantly turn up to bitch and whine in all Larry's thread on the subject of junk-DNA is evidence against your position that creationists are somehow fine with there being junk-DNA.

Mikkel Rumraket Rasmussen said...

If you're totally fine with there being junk-DNA due to your laughably inept and totally ad-hoc rationalization about "the fall" (what the fuck theological reason is there for thinking "the fall" would affect the genome anyway? This shit is just pulled out of your collective asses after-the-fact), then why is this discussion even of any consequence to you? Shouldn't you just sit back and watch?

Tell us, by the way, how much junk-DNA "the fall" has produced and tell us how you know that. Tell us how you know it even produced ANY junk-DNA. How is the claim tested? Can we re-run "the fall" in the laboratory to verify the claim that "sinning" against god is degrading DNA? Do magical beams of DNA-degrading rays shoot out of your dick if you have extramarital sex?

Mikkel Rumraket Rasmussen said...

Did large waves of magical anti-divine sin-beams shoot out of the Garden of Eden and hit the nutsack and ovaries of all species around? Why'd it only happen to produce junk-DNA, instead of making billions and billions of organisms infertile and prone to cancers? Can you pinpoint a moment in history when every living organism had large tumors due to DNA-degrading sin-beams permeating the cosmos?

Why would two people gaining knowledge even affect and degrade DNA of anything? None of it makes sense you religious lunatic.

gnomon said...

M.

1. Based on what evidence can you say that human genes encounter more functional constraint than it's homolog in fish or yeast?

mutation cause tissue or cell type specific diseases in humans, which means many cell types would tolerate such mutations while some not. The inference would be the more the cell types for an organism, the more functional constraints on genomes.

-Doesn't that massively depend on the gene & the selective pressure? What about duplicate genes?

Yes, but mostly depend on physiological selection or internal system construction requirements, which is a concept completely missing in the modern synthesis. The Third Way scientist Denis Noble has made similar point.

-Is that true for most genes? (evidence please)

Genetic equidistance at the proteomic level as shown by one of our preprints this year is the best evidence. Such reality has no other sensible explanation other than our MGD thesis.

-Is that true for most non coding sequence? (evidence please)

Genetic equidistance at the whole genome level, which would be mostly weighted by non-coding, also holds in cases where it has be analyzed. Thus, orangutan is equidistant to gorilla, chimp, and human.

2. Does the 'maximum diversity' (whatever that should tell me) in a clade not depend as well on the age of the clade and the generation time in that clade?

Yes. Only after enough time when thing reached maximum or optimum. The fundamental single difference between the MGD and the modern synthesis and the junk DNA thesis is that one treats most observed molecular variations (after multimillion years of evolution) as being at optimum level while the other still increasing in a time dependent way. That is really easy to distinguish, isn't it? Well, for half a century, no one bothered. Only we did that in recent years, and the results could not be less clear.

-Are mammals not derived from bacteria? Couldn't that be the explanation for the similar numbers of 'in between difference' for bacteria and 'between difference' for bacteria and mammals?

Yes, in a way. You can treat human as a special kind of bacteria, of course a most widely separated one from other bacteria. Thus, distance between human and bacteria should equal to the maximum distance within bacteria. The same logic applies to treating human as a fish or a mammal. Distance between human and fish equals the maximum distance within fishes, which can be easily shown.

3. And again:
-What does more complex mean? How do you measure it ? (a reproducible procedure, please)

Count the Number of cell types. for technical reasons, this cannot be precisely done at the moment. But in most cases, such precision is not necessary, e.g, compare human with chimp or with C. elegans.

-Who is more complex: a dog a cat or a squirrel? Who is more complex: a Chinese or a European? Who is more complex: A salamander with a genome size of 100Gb or a salamander with a genome size 20Gb?

We will have interesting things to say in a future paper backed up with lots of genetic evidence on the Chinese and European question. The kind of unity between genotypes and phenotypes well known to characterize these people is amazing. One can only marvel at how orderly everything truly is.

To be useful for solving mysteries at this point, the dog and cat etc question is trivial at this point. Genome size is not a good measure of anything.

gnomon said...

@Chris B
So do phylogenetic trees then reflect the hierarchical order of complexity of organisms rather than their genetic relatedness?

Present trees indeed reflect one of two things or both: common environmental selection and common physiology. Only by using slowest evolving sequences, which are truly neutral at least for time period concerned, we can build true phylogenetic trees. I heard from a plant geneticist at the recent PAG meeting in San Diego that phylogenetic trees built by choloroplast genomes reflect perfectly geography rather than real ancestry relationships. That is apparently old news in the plant community but I need to track some citations. Another example is ancient DNA work showing the striking repeated pattern of no genetic continuity between ancient people and modern living in the same location. Well, ancient environments are certainly very different from today's. that is why people see what they see. We will soon submit a paper to show that there are really few surprises in terms of DNA work not consistent with well established facts collected by archaeologists and paleontologists.

How do you quantify and assign values of 'complexity' to species to do your analyses? How do your determine what a clade is?

Cell type numbers. Phelogenetic trees is possible but only if one uses the informative or truly neutral genes (for the time period concerned).

How does this concept relate to genome size?

It explains why simple species like protists have a genome size variation ~5000 times larger than that of mammals. Goto my blog for a recent piece on this. There is also a striking base composition variation pattern found last year, as highlighted on my blog. Bacteria or protists have much larger variation in base compositions (A% in a strand, e.g.) than primates. Third Way professor Bernadi has long argued for isochores and base composition constraints, all to the dismay of neutralists. This new study not only supports Bernadi but also our MGD, showing simple species have less constraints on base compositions, or in short, on random errors in their building parts.

Anonymous said...

Mikkel Rumraket Rasmussen, I don't want to be misunderstood as endorsing any creationist thought. However, the creationists who think our genes have degraded after the fall are probably not thinking in terms of "sin-beams" but in terms of the presumed perfection of the original genotypes no longer being supported by god's healing power, and thus degrading each generation.

In other words, they're wrong but in a different way than you seem to be thinking.

Mikkel Rumraket Rasmussen said...

Oh, so Adam and Eve suddenly knowing something they did not previously know, caused god's magical healing-beams to stop permeating the cosmos because reasons. Cool. I guess knowing shit is bound to have such an effect. Happens all the time. You suddenly come to have an understanding of something and god mysteriously fails to do his magic.

gnomon said...

@aceo..
check out our new paper on mitochondria coevolving with nuclear genome. Compatibility between mito and nuclear genome

Chris B said...

BC,
I already explained to you above how you got it wrong. Repeating yourself does not help. Mikkel has pretty thoroughly explained it to you again, so I won't belabor the point.

To summarize, mutational load is not a problem for evolution. It is one of several lines of evidence in support of a large proportion of our DNA being nonfunctional. Scientists only reluctantly came to this conclusion based on empirical evidence. They also have no vested interest in how much nonfunctional DNA we carry.

ID/creationists on the other hand have relentlessly tried to pound the square peg of no junk DNA into the round hole of reality, because they have a priori decided the designer is too clever and efficient to give us so much nonfunctional DNA.

Fair Witness said...

gnomon said " One can only marvel at how orderly everything truly is."

That is a true "tell" for theological bias.

lutesuite said "No, you wouldn't. (want to read gnomon's papers) You have been warned."

You were correct. I regret it already.

gnomon said...

Truly strange way of thinking! Why is that not a mathematical bias or scientific bias? Science is all about laws and orders, is it not? I happen to have a taste for law rather than for random chance discovery of novelty or this protein structure or that structure. If biologists are used to stamp collection or finding random things like a 4 leaf tree in a species characterized by 3 leaf, does that say more about the nature of biology or the nature of biologists being no mathematicians or physicists? At the time of Darwin or even Kimura, were the best science talents in biology or in math and physics? Do we all not wish biology to be more like physics rather than more like social sciences?

Jmac said...

Genomon,

Do you still believe evolution happened or is happening now? If yes or no, please explain why!!!

By reading your comments-they are by far the most provoking in a very long time on this blog-I still sense some bias in them. You try to overthrow Darwinism, and yet you are left with more problems to explain than Darwinists. What are you trying to accomplish and for what reason? I will ask you about the evidence after that.

whimple said...

Why we still don’t have personalised medicine, 15 years after sequencing the human genome. She is a postdoc in Molecular Genetics at the University of Oxford so the subject is within her area of expertise.

Uh, no. Development of medicines, whether personalised or otherwise, isn't even vaguely within the area of expertise of a post-doc in Molecular Genetics. Here's the list of FDA-approved personalised medicines just to start with: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm

BC said...

Mikkel Rumraket Rasmussen,

Me: "Genetic load is a problem, so the proportion of junk is not "another part of genomic knowledge to be learned". A large percentage of junk DNA is shoehorned in to uphold the belief in evolutionary theory."

"No, junk is implied by genetic load."

You conflate the evidence (genetic load) with the evolutionary implication (junk DNA). You're shoehorning.

"That in itself might not have been enough to really prove there was lots of junk, but then this isn't all there is to the junk-DNA argument either."

No, but it's the main argument.

"The genome has been sequenced, we know what most of it is. Introns, defective transposons, pseudogenes and so on."

Oh good. Do you know how to cure cancer? Downs Syndrome? Cystic fibrosis? Why can't you just be honest and admit that in fact, we don't know what most of it is?

"Then there's the fact of it's extremely low expression levels, the lack of sequence conservation, that in studies of mince large swathes can be removed without effect."

Did you know that the "large swathes" that were removed were the "conserved sequences" (not the "junk")? Do you understand the implications?

"There's the comparative genome-size variations between different species etc. etc."

That's a (related) topic for another day.

"Simply put Christ is absolutely right"

A trueism not in dispute. Chris on the other hand..Let's just say he (or she) doesn't read Sandwalk very often.

"It's the evidence that overwhelmingly supports the case for lots of junk, not some kind of imagined ideological committment to junk to "save" evolution from genetic load."

Once again you conflate the evidence with the evolutionary implications. Please stop doing that.

Me: "I've never seen a single creationist claim that our genome has not degraded from its original state (even if we could know what that might look like). Some might argue for low amounts of junk, but whatever the future reveals as the final proportion is a non-issue. "

"Utterly false"

If it's utterly false it should be easy to find (let's say three) creationists that claim our genome is in a pristine state. After that, please get in your time machine and bring back the evidence for what the future reveals as the final proportion.

"The final proportion is the MAIN issue."

Perhaps you shouldn't make that the MAIN issue (until you're back from your time travelling trip).

"The fact that creationists aren't (mostly) so incredibly deluded they still think even the vitamin c pseudogeone is functional (oh, wait!...) isn't a point in their favor. The general idea from creationists is that their god would not design a genome that is MOSTLY junk."

Even if that were true, it's not a scientific idea. So why do you care? Just sit back and watch.

For fucks sake, the fact that you people constantly turn up to bitch and whine in all Larry's thread on the subject of junk-DNA is evidence against your position that creationists are somehow fine with there being junk-DNA.

I didn't "bitch and whine". That's on you.

gnomon said...

According to relativity, if you sense bias in someone, it could mean just as well that you are biased but the other not. FYI, I have this phrase as part of my blog name: disinterested search for the true law of evolution wherever it may lead. So, I certainly do not see myself biased in any non-scientific way. And I have seen too many biased biologists. For biased people to communicate with non-biased or oppositely biased people, it is only fruitful if the communication is only focused on specific details or facts rather than philosophical issues. I do not want to claim or say anything not justified by verified facts. Having seen way too many theorists with useless ideas and claims, I want to be unique in being detail oriented and useful in helping moving bench research in concrete steps. So, the thing I do claim and I hope you can see for yourself is this. There is a century old mystery of what determines genetic diversity. The half century old phenomenon of genetic equidistance is part of that same mystery. The MGD thesis, in combination with the proven virtues of Darwin's and Kimura's theories, has finally provided a correct solution. That genetic diversity today is largely at optimum dynamic equilibrium is a bold, specific, and easily verifiable or falsifiable claim. It has in fact been verified in several different ways by our work in the past 8 years. That claim or finding or reality has great practical impact on solving a variety of biological problems, including phylogenetic trees and the genetic basis of complex traits and diseases. If you cannot see it but are interested to know how, I can help. If you do not wish to see, I can understand and accept but then there is nothing I can do for you. People should look at the facts and draw their own conclusions, and the answer to your questions should be obvious from my writings so far. Yes, evolution happened and is happening right now and will continue. Why? Precisely because things are mostly at optimum dynamic equilibrium.

Anything Darwinism has explained that has satisfied the minimum standard of science is also automatically explained by the MGD theory because it includes Darwin’s proven portion as part of the theory. On top of that, the MGD theory explains a lot more and is more useful in directing daily biological research in general not just limited to evolutionary problems. So, I do not see your point that the MGD has explained less than Darwin's.

Faizal Ali said...

BC drools insipidly:

You failed to present any evidence that indicates my claim regarding genetic load is incorrect or that I've misunderstood the concept.

I don' need to. You've done a great job of providing the evidence all by yourself. Much obliged.

Anonymous said...

BC wrote, regarding the genome: "Oh good. Do you know how to cure cancer? Downs Syndrome? Cystic fibrosis? Why can't you just be honest and admit that in fact, we don't know what most of it is?"

1. But we do know what most of the genome is; dead transposons, dead viruses, mRNA read back into the DNA, and remnants of old duplicated genes that mutated away from function.

2. Knowing what's in our genome in much more detail than we know now, isn't going to lead directly to cures for cancer, Downs syndrome, cystic fibrosis, or other illnesses. It will give us good clues, but that's all. For example, biologists know a great deal about the many different mutations that can cause cystic fibrosis and understand a good deal about the function of the effected protein, but we still don't have an cure for cystic fibrosis (though treatment has much improved).

Tom Mueller said...

@ Georgi & @ Barb

Maybe I am out of date and betraying undue naïveté - but don't research labs still have "Journal Clubs"?

Tom Mueller said...

Hi Bryony

I have to jump to your defense. Clearly you are not guilty of such blatant ignorance as your detractors would ascribe.

Your earlier answers clearly indicate you appreciate subtleties of distinction - i.e not all "functional" DNA is "coding" i.e. translated into protein & scientists have know that fact for a long time.

Indeed any high school student would know that Jacob and Monod elucidated the Operator region in the Lac Operon back in the 60s, for crying out loud.

FTR - my own high school students understand that 90% of single-letter differences in sequences that are associated with various diseases fall outside of protein coding regions when we broach the tricky question of how best to define a genotype vs phenotype!

The problem is "that is not what you said"! I think you can be faulted for poor choice of words in your attempt to "dumb down" a description of your research to the non-scientific lay public.

The word "junk" has become a bone of contention due to the hype of some (not all) individuals in the ENCODE crowd. As a result - you are the victim of unfortunate guilt by association.

If you are guilty any sin of omission - it would be your lack of awareness of how some in the scientific community continue react most negatively to even a whisper of a hint of ENCODE.

Now you know.

Congratulations on your successful and prestigious grant bequest and best regards in wishing you a successful career

Georgi Marinov said...

They still do.

Georgi Marinov said...

Tom Mueller Saturday, January 23, 2016 12:00:00 AM

Clearly you are not guilty of such blatant ignorance as your detractors would ascribe


I don't think you're reading it right -- this isn't really about equating functional DNA with coding DNA (I personally never said that), the problem is the lack of understanding of the issue in its general context.

Tom Mueller said...

Hi Georgi,

I think you misunderstood my defense of Bryony and I did not have your remarks in mind as I composed my last comment above.

It is clear to me that Bryony is in greater command of the science than she is credited.

I think the only context at issue here is the bataille royale some present are waging with some in the ENCODE crowd and Bryony inadvertently got caught in the cross-fire and represents collateral damage.

You will need to excuse me now while I run and duck for cover in anticipation of the wrath of others present.

best regards

Tom Mueller said...

... but before I take my leave.

I leave this interesting gem for Piotr which should be up his alley.

http://www.bbc.com/news/uk-35358487

back to lurk mode - I just needed to rescue a damsel in distress.

best regards to one and all

Tom Mueller said...

... oops last postscript to Georgi

re: I don't think you're reading it right -- this isn't really about equating functional DNA with coding DNA (I personally never said that)...

But in fact - that is in fact what Bryony said even though no high school Biology student would ascribe to such an over-simplification

Bryony is guilty of over-simplification and an unfortunate poor choice of words is all.

I just wanted to be clear here.

Georgi Marinov said...

There is one more thing I wanted to mention:

This episode illustrates one rarely understood but devastating fact about modern science, and it is that the postmodernists have won. Without ever winning a single intellectual battle -- scientists defeated themselves quite voluntarily. What we have today is to a significant extent a postmodern science and it was scientists who made it so, by:

1) Refusing to let go of a celebrity culture in which your worth is measured in how many tokens (i.e. papers) of what perceived value (i.e. published where) you have collected over time and how much publicity you have managed to attract.

2) Refusing to acknowledge the unsustainable nature of the current academic system -- successful PIs have dozens of students and postdocs working for them ("for" being a key word) and many of those people are working with the vague promise that they will one day be in the same position as their PI. Which only works as long as the system is expanding and more and more such positions are opened. But once it stops expanding, as it did some time ago, it's in deep trouble, because then competition along the lines of the previous point becomes really cutthroat and all sorts of pathological from the point of view of doing the best science possible behaviors become commonplace. And then we have:

3) The tennis match between authors and reviewers in top journals that has been played countless times over the decades. The culture is such that the reviewers feel they have to ask for more and more stuff in the paper, while the authors are trying to trick the reviewers into accepting it, and it becomes a game of attrition and manipulation of facts in which the main victim is objective truth (everyone who has gone through that sufficiently many times knows what I am talking about). Quite contrary to what the idea behind having peer review in the first place is supposed to. That's also how we end up with so many high-profile papers that one has to read very carefully and knowing a certain secret code language so that all the obfuscations can be stripped from the text and one can have some hope of understanding what the results actually are.

The end result is that young scientists grow up with a mentality that science is a game, which you play to win, not really a quest towards objective truth. I may catch a lot of heat for this comment, but it's not just my personal observation (and you can accuse me of projection here, I will not argue against that, I am genuinely afraid I will/have become like that too), more senior and experienced than me people share the same concern (side note: in this case, this is a valid use of the input of such people).

That's how misrepresenting the objective scientific truth on junk DNA becomes perfectly fine as long as it's perceived as good "hook" for the general audience. After all, the very same thing goes on when writing scientific papers, it's just more subtle and difficult to spot.

Tom Mueller said...

Hi Georgi

I agree hype to the point of hubris have always been a feature of science as a competitive endeavor, this is nothing new but may have intensified as of late.

I also do not think that Bryony was guilty of "misrepresenting" - but rather over-simplifying with jargon that once was but no longer is acceptable while targeting the general public as an audience.

Your other points are well taken:

In the Boston area alone, there more than 8,000 aspiring postdocs — largely in the biosciences!

http://www.bostonglobe.com/metro/2014/10/04/glut-postdoc-researchers-stirs-quiet-crisis-science/HWxyErx9RNIW17khv0MWTN/story.html

Meanwhile - it would appear that post-docs and PhDs are as dispensable as galley slaves

http://www.economist.com/node/17723223

best regards

Tom Mueller said...

final postscript (this time I mean it)

here is an intriguing paper that meets more than one of Larry's essential criteria for weighing in on the "junk" DNA debate

Conservation is not an issue if conserved and essential lncRNA–genome interaction regions are relatively small and interspersed with non-conserved spacers.

http://genesdev.cshlp.org/content/30/2/191.full

Maybe it too is guilty of hype and hubris - I am in no position to judge.

I understand Larry's earlier contention:

“The most important question in NOT whether some of them [lncRNAs] have a function—that was demonstrated 30 years ago. The important question is whether the majority, or even a substantial minority, have a function.”

I posit that any eye-brow raising contention along the lines of "
Actually we DO have a pretty good idea about most of our genome. " may be premature given knock-out studies may not detect redundancy in function.

Finally Larry's own links indicate there was contentious debate up to the 90s regarding the size of the human gene repertoire - and even though Lewin's 2nd edition text suggested 40 000 as a reasonable number, the majority of standard texts were citing larger numbers along 100 000 despite cogent mathematical caveats to the contrary. The problem with maths - often maths can be misleading such as the "old saw" that "mathematically" a bumble-bee is incapable of flight and yet there it still flies.

So Bryony's citation of "surprise" in this case is not misplaced IMHO.

That said - I agree with Georgi and Larry both that youngsters in the field should spend more time mastering, in better detail, the historical details of their field.

best regards

Faizal Ali said...

I hope BC isn't waiting for the Intelligent Design "scientists" to answer any of those questions. He'd be in for a long wait.

Faizal Ali said...

Oh, good. Eric and gnomon are talking to each other. Maybe they can leave the board to have a private conversation, and allow the adults to have an intelligent discussion without interruptions.

Dave Carlson said...

Hi Tom,

I actually started a conversation about that excellent Genes & Development paper by Quinn et al. over at the Skeptical Zone (http://theskepticalzone.com/wp/conservation-and-function-of-long-noncoding-rnas/) if you'd like to participate. :)

Chris B said...

"You conflate the evidence (genetic load) with the evolutionary implication (junk DNA). You're shoehorning."

No, BC, the genetic load argument is a logical inference based on empirical data. Go back and read Dr. Moran's essay on the subject, and follow the facts.
Shoehorning is trying to cram a priori beliefs into established facts. For example, claiming that a supernatural being created one man and one woman who are the progenitors of all humans on earth and that their genomes were once perfect and stable, but after they ate the wrong fruit in the perfect magical garden they were living in their genome began to degrade and that is why god inflicted his creation with horrible diseases and suffering. Somehow this affected all living creatures as well. You have no evidence for any of that fairy tale, so it does not serve as an explanation for the current state of your genome. THAT is shoehorning.


"No, but it's the main argument."
No, it's not the main argument. It isn't even the most direct argument. Several lines of evidence point to much of our genome being nonfunctional. Go to the 'Genomes & junk DNA' theme on this site and start reading.

"Oh good. Do you know how to cure cancer? Downs Syndrome? Cystic fibrosis? Why can't you just be honest and admit that in fact, we don't know what most of it is?"
We know what it is, although we don't know how every bit of it works. That is the type of research Dr. Graham is working on, for example. Are you even paying attention here? And for the record, we know what kinds of genetic anomalies cause Down syndrome, cystic fibrosis, many cancers, and many other genetic diseases as well. And scientists are working to find cures for these diseases all the time.

""It's the evidence that overwhelmingly supports the case for lots of junk, not some kind of imagined ideological committment to junk to "save" evolution from genetic load."

Once again you conflate the evidence with the evolutionary implications. Please stop doing that."

How do you figure Mikkel conflated anything? Explain please.

"Even if that were true, it's not a scientific idea."
No, BC, it is true and it is a scientific idea: that our vitamin C synthesis genes are functional. It's just a bad scientific idea, because it is wrong.

Larry Moran said...

Finally Larry's own links indicate there was contentious debate up to the 90s regarding the size of the human gene repertoire - and even though Lewin's 2nd edition text suggested 40 000 as a reasonable number, the majority of standard texts were citing larger numbers along 100 000 ...

It's true that popular opinion was overestimating the number of expected genes. Textbook writers either didn't do their homework or preferred to reflect the popular view over that of knowledgeable experts.

I faced the dilemma in 1994 when I opted to say that "mammalian genomes may contain about 50,000 genes." I was pretty sure that the actual number would turn out to be closer to 30,000 but popular opinion at that time was talking about 100,000 genes.

Professors won't buy your textbook if they think you don't know what you're talking about—even if you are right. This is the most frustrating part about writing textbooks.

However, when you are writing the history after publication of the human genome sequence you owe it to your readers to tell the truth. The experts were predicting about 30,000 genes and that's what was found. You can add the caveat that most scientists were unaware of the scientific literature so they were surprised.

The way Byrony Graham describes it conveys the impression that the best scientists didn't have any idea that most of our genome is junk and there were only 30,000 genes. That makes it sound like scientists aren't very smart and there's a big mystery ("dark matter") that needs to be solved.

If you were part of the group that was unaware of the literature—and were surprised in 2001—then chances are you still haven't caught up and you are still looking for ways to make humans special [The Deflated Ego Problem].

I suspect that Bryony Graham and her colleagues fall into that category. I bet none of them have read The Origins of Genome Architecture but they still think they are experts on the evolution of the human genome.

Larry Moran said...

Georgi Marinov says,

The end result is that young scientists grow up with a mentality that science is a game, which you play to win, not really a quest towards objective truth. I may catch a lot of heat for this comment, but it's not just my personal observation (and you can accuse me of projection here, I will not argue against that, I am genuinely afraid I will/have become like that too), more senior and experienced than me people share the same concern (side note: in this case, this is a valid use of the input of such people).

I agree. I also agree with you that it's my generation that's to blame for this mess. For some reason we stopped demanding that our students understand science as long as they produced results in the lab.

I've been trying to get my colleagues to rectify the situation in my department but nobody wants to change the system. It's considered in poor taste to challenge someone in a seminar if they say something stupid, especially if it's a student or a post-doc.

Nobody wants to be "objective" when writing a grant. The last thing you want to do in a grant is challenge the existing paradigms or the popular misunderstandings. That's deadly. It's the exact opposite of how science is supposed to work. What we SHOULD be doing is taking all those grants that just want to confirm existing paradigms and toss them in the garbage.

Imagine how much fun it would be if we only funded renegades and mavericks ... as long as they are smart and demonstrate that they understand the literature!

Arlin said...

Graham clearly wrote the article under the mis-impression that "junk DNA" means "non-coding DNA". I can understand how a reader who is desperate to find adaptationists to criticize might fail to see that, and instead accuse Graham of being an adaptationist pollyanna. However, the objective reader could easily discover the mistake.

This mistake could mislead readers into all sorts of things.

However, if one goes back and mentally replaces "junk DNA" with "non-coding DNA", then the article becomes sensible. In particular, the article does not imply that all non-coding DNA (she calls it "junk DNA" is functional. That is, if one goes back to reconstruct Graham's thinking, her error is to use the wrong term, not to assume that non-coding DNA is entirely function or entirely non-functional.

Jon Fleming said...

Creationists love "we don't know everything therefore we know nothing".

Arlin said...

Good points, Georgi. Regarding the point about the peer review system, I think that if a person has skill and imagination, then-- unless the system is completely corrupt-- it is possible to play the game with integrity. Getting along in a politicized system and maintaining integrity are not necessarily incompatible-- it's a matter of being as clever as serpents while staying as innocent as doves (cf. Matthew 10:16).

Tom Mueller said...

@ Larry

... as I mentioned earlier:

I agree with Georgi and Larry both, that youngsters in the field should spend more time mastering, in better detail, the historical details of their field.

I think we agree more than we disagree - but I still had to rescue a damsel in distress whom I believe was being treated a little unfairly.

I am certain her presentation at journal clubs differs significantly from her public relations releases to the lumpen-proletariat.
In any case... I am sure Bryony will be somewhat more circumspect in future! (... with a tip of the hat in your direction for playing the important role of Socratic gadfly)

The whole truth said...

"lumpen-proletariat"? Really?

So it's okay for Graham to deliberately spew bullshit to the "lumpen-proletariat", so as to 'hook' them into reading her articles as long her "presentation at journal clubs differs significantly", eh?

Damsel in distress? Are you serious? Haven't you heard of women's lib, demands for equality, and all that jazz? If Graham is "in distress" it's because she put herself there, and her responses above show arrogance, not distress.

https://en.wikipedia.org/wiki/Lumpenproletariat

The whole truth said...

I hope that gnomon does not leave. I'm not saying that I agree with him but I think that he should be heard. If he's wrong, it should be shown by presenting scientific arguments and evidence that refute his claims.

/u/lapapinton said...

Hi everybody. I'm a biology undergrad, and Young-Earth Creationist who greatly enjoys Larry's blog.

I was wondering, would somebody be willing to take a look at an essay I wrote, titled "An overview of Junk DNA and a recent controversy concerning the human genome":

https://docs.google.com/document/d/1_TR8aSv3PD855d6vaPDvied23MmesoaprIzGO3kzSaA/

I've already submitted it and received a decent mark for it, but I was wondering whether anybody would care to educate me on any factual errors that may be contained therein?

Kind regards, /u/lapapinton from reddit.

Aceofspades said...

Hey /u/lapapinton :)

Well done... This is one of the better representations of the junk DNA debate that I've seen presented by a creationist

If I may, I'd like to make a few suggestions:

The term predates Susumo Ohno, although I think it's fair to say that he was the one to popularise it.

Ohno didn't only use the C-value paradox to argue for junk - the other issue he raised was genetic load. He raised the fact that observations showed that each gene locus faced a 10^-5 per generation probability of sustaining a deleterious mutation which implies that we must have significantly fewer that 100,000 genes.

Much of the rest you've written here appears to be largely correct but I have concerns about some of the important parts of the story that you haven't mentioned which I would have included.

Regarding the bulk hypothesis: Cavalier-Smiths “nucleoskeletal DNA”, one of the major problems with this idea is once again the C-value paradox. Some salamanders for example have genomes 9x larger than others. Why is it that some salamanders will need nucleoskeletal DNA to increase the cell's volume while other salamanders survive just fine with a genome almost 1/10 the size.

It wasn't just Dan Graur who critiqued the ENCODE results. The ENCODE results were met with a profusion of papers calling out their misleading use of the term "functional".

In 2013, the ENCODE team backtracked a little with the publication of this paper, effectively admitting that their usage of the term "function" doesn't necessarily imply that something is functional.

http://www.pnas.org/content/111/17/6131

"However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional."

You also didn't mention (or perhaps you weren't aware of) this most recent paper (July 2014) which has come up with the best estimate to date for the amount of functional DNA in the human genome (8.2%):

http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004525

Do you mind if I ask: Do you attend one of those Christian colleges which teach creationism?

/u/lapapinton said...

Thanks for the helpful comments and links.

>Some salamanders for example have genomes 9x larger than others

Yes, I remember reading somewhere that the c-value paradox is particularly acute in amphibians.

>Do you attend one of those Christian colleges which teach creationism?

No, I attend a public university.

gnomon said...

/u/lapapinton

I tell my students whenever they go into a new field of study, they should first critically examine the assumptions of the field. Your paper is a good summary of what are on the surface but is unfortunately just that. The junk DNA debate is a useless philosophical exchange between biased researchers. It really did not touch what really matters because the experimentalists knew very little about the neutral theory, which is really the basis for the junk DNA notion. To disprove junk DNA is to wipe out an entire field of molecular evolutionary and population genetics, invalidating e.g., nearly all the gene trees of life. The stake is much higher than you have imagined. The neutral theory happens to have lots of mathematics, which has unfortunately scared off nearly all the experimentalists in biology. Thus, they really cannot possibly do it right in their fight with the neutralists. Relying on experimental work to prove function requires years and years of work, too long for the neutralists to have any fear of being proven wrong in the near future or in their lifetime.
Fortunately there are far more effective ways to do that if one knows the neutral theory well. A theory gives many predictions and has always assumptions. And one can easily disprove any incomplete theory by attacking the assumptions or by verifying one of its predictions false. If one does that with the neutral theory, the theory stands no chance of passing even just a semi-critical eye. If you look at the list of 50 scientists associated with Third Way of Evolution , you would find that there is only one among them that had done that or has specifically challenged the neutral theory, who happens to be me. I advise that you examine the assumptions of the field and see if they make any sense. My recent preprint could help with that. Old riddle genetic diversity

If you have doubts about the validity of my viewpoints, you can ask Larry or any experts who follow his blog why they have not yet ridiculed any one of my dozen peer reviewed papers in the past 8 years or any specific scientific points that I have raised. In striking contrast, Larry is fully of energy in harassing researchers who have only published like one or two minor works on the issue and are much less threatening to the junk DNA bandwagon. Why the strange choice of targets?

gnomon said...

My preprint has this to say on conservation, genetic load, C- value paradox:
Nonconservation means non-function. This assumption treats many genomic elements as neutral such as repetitive and viral elements and is key to the conclusion of only 8% functional genome in humans [40]. However, to use conservation as an index of function is only measuring one of two kinds of sequences, the essential ones for internal system physiology that have little to do with adaptation to the outside environments. To maintain the long term integrity of the system, such sequences cannot change. For living fossils to be possible, these sequences should be highly stable. On the other hand, sequences involved in adaptation to environments must be fast changing because environmental changes are usually fast. Flu viruses escape neutralizing antibodies every few years, and the fast changing non-conserved sites in these viruses are absolutely critical for their survival but not essential for their physiology.

Genetic load. One of most commonly used arguments for junk DNA is that if mutations are deleterious, the observed mutation rate would be too fast for human to tolerate such a high mutation load burden [36]. However, the genetic load concept is based on the untrue assumptions of independent mutations and of natural selection always working on single loci. If mutations are negatively selected in a collective way whenever a threshold of MGD is surpassed, the mutation load would never materialize. This is just like computers eventually crash due to long term use and the accumulation of all kinds of small random hits to its parts. Evidence for the deleterious nature of too much genetic noises has recently been found [6-11].

C-value paradox. Genome sizes vary greatly and do not correlate with organismal complexity. Some plants like onion have much greater genome size than humans, which has been used to favor junk DNA idea [36]. However, houses can be small or large and so the number of parts involved can also vary from small to large. Genome as a whole is a building part, and this part can vary in size is just like any parts should have an allowable STDEV. Along this line, it fully explains why complex mammals have much less variation in genome size relative to lower species such as fish or plants. The simple unicellular organism protozoa kind has a genome size variation range with one end ~20000 fold larger than the other end whereas mammals only less than 10 fold. The real significant question on genome size should be why the protozoa kind has such huge variation in genome size, rather than why the onion has such a huge genome.

Similar brief comments can be found here why the surprising pattern of no genetic continuity and also here 8.2% functional DNA???

BC said...

Chris,

"No, BC, the genetic load argument is a logical inference based on empirical data. Go back and read Dr. Moran's essay on the subject, and follow the facts."

Genetic load arguments are an attempt to rationalize the directly observed number of new mutations per generation. Professor Moran says that this number is "unacceptably high". In order to shoehorn the belief in evolutionary theory into this "established fact", junk DNA is the rescue device.


"Shoehorning is trying to cram a priori beliefs into established facts. For example, claiming that a supernatural being created one man and one woman who are the progenitors of all humans on earth and that their genomes were once perfect and stable, but after they ate the wrong fruit in the perfect magical garden they were living in their genome began to degrade and that is why god inflicted his creation with horrible diseases and suffering. Somehow this affected all living creatures as well. You have no evidence for any of that fairy tale, so it does not serve as an explanation for the current state of your genome. THAT is shoehorning."

Whilst degradation would be consistent with the Fall, there's no theological reason to assume that genomes were "once perfect". Since we don't know what the original condition was, there's no "shoehorning" necessary. You ask me not to repeat myself, but continually demonstrate that you can't understand my basic point.


"No, it's not the main argument. It isn't even the most direct argument. Several lines of evidence point to much of our genome being nonfunctional. Go to the 'Genomes & junk DNA' theme on this site and start reading."

Like Mikkel, you conflate evidence with assumptions (introduced due to the implications for evolutionary theory). The direct arguments are based around pseudogenes and TEs, etc. But these are not easily shown to be non-functional; that is assumed (falsified if function is demonstrated, as has happened many times). If future studies reveal such assumptions to be false (to a significant degree), then the observational evidence for genetic load refutes modern evolutionary theory. That is why the genetic load argument is so important (at least for this blog).


"We know what it is, although we don't know how every bit of it works. That is the type of research Dr. Graham is working on, for example. Are you even paying attention here? And for the record, we know what kinds of genetic anomalies cause Down syndrome, cystic fibrosis, many cancers, and many other genetic diseases as well. And scientists are working to find cures for these diseases all the time."

You accuse me of not paying attention, but let's see what Dr. Graham actually wrote:

"It's because, over a decade after the first draft of the human genome was published, we still really don't have any idea of what most of it actually does."

And:

"I think the bottom line is that there are so very few detailed functional studies of specific regions of the genome that the topic remains open."

It's not just a case of dotting the i's and crossing the t's. The fact is that most elements in the genome have not been analysed for function (partly because this is very difficult to do).


"How do you figure Mikkel conflated anything? Explain please."

See above (where you do the same thing).


"No, BC, it is true and it is a scientific idea: that our vitamin C synthesis genes are functional. It's just a bad scientific idea, because it is wrong."

Even though I've had to repeat myself countless times, people here seem to think I'm arguing that the entire genome must be functional.

To restore context:

"The general idea from creationists is that their god would not design a genome that is MOSTLY junk."

To test this we'd need to know what God would or wouldn't do (in terms of our genome). We don't know that, so it's not a scientific claim.

BC said...

Jon Fleming,

Evolutionists love "we know most things, we're just sorting out the details".

This is ably demonstrated by bwilson295 (among others):

"Knowing what's in our genome in much more detail than we know now, isn't going to lead directly to cures for cancer, Downs syndrome, cystic fibrosis, or other illnesses. It will give us good clues, but that's all."

If this is what modern evolutionary theory implies, it should carry a public health warning.

judmarc said...

@BC - You keep talking about shoehorning while describing its opposite.

Genetic load is a fact. 130 mutations per human generation on average is a fact. The "onion test" (even closely related species can vary wildly in the sizes of their genomes) is a fact. Much of the human genome being composed of stuff like retrotransposons, LINEs, SINEs, etc., is a fact.

So what we have is not a belief in search of facts, but facts in search of an explanation.

Having pointed out yourself that any "explanation" that purports to rely on the intent of a deity is not a scientific claim, what is your scientific explanation for these facts?

Chris B said...

BC,
"Genetic load arguments are an attempt to rationalize the directly observed number of new mutations per generation. Professor Moran says that this number is "unacceptably high". In order to shoehorn the belief in evolutionary theory into this "established fact", junk DNA is the rescue device."

No. The mutation rate has been independently measured many different times using several different methods. They all vary, of course, but generally fall in the same order of magnitude. That is called empirical data, and it poses no problem whatsoever for evolutionary theory, or genetics, or cell biology, or physiology, or...

If the majority of the genome was constrained by sequence, this would be an unacceptably high mutation rate.

Chris B said...

BC,
"Whilst degradation would be consistent with the Fall, there's no theological reason to assume that genomes were "once perfect". Since we don't know what the original condition was, there's no "shoehorning" necessary. You ask me not to repeat myself, but continually demonstrate that you can't understand my basic point."

Please don't point to 'once perfect' and use that to weasel out of your absurd claims. We could just as well say 'more perfect' and the argument remains unchanged. You silly alternative of 'the fall' and the rest of your theology is a fairy tale with no evidence whatsoever to support it. So yeah, that's shoehorning your religious beliefs into reality.

Chris B said...

BC,
"Like Mikkel, you conflate evidence with assumptions (introduced due to the implications for evolutionary theory). The direct arguments are based around pseudogenes and TEs, etc. But these are not easily shown to be non-functional; that is assumed (falsified if function is demonstrated, as has happened many times). If future studies reveal such assumptions to be false (to a significant degree), then the observational evidence for genetic load refutes modern evolutionary theory. That is why the genetic load argument is so important (at least for this blog)."

I'm not conflating evidence with assumptions. I think that broken genes, broken transposable elements and broken fragments of viral DNA integrated into our genome are not essential functional elements. Is that unreasonable? Your claim that these are functional would carry assumptions at least as onerous as mine. You clain function has been been demonstrated for these elements "many times". What percentage of our genome has been proven functional in this way? I'm not saying it is impossible for these elements to acquire a function, how often has this actually happened? What do the scientific studies tell us, BC? The genetic load argument remains important for anyone interested in genome function, not just this blog.

Chris B said...

BC,

"Even though I've had to repeat myself countless times, people here seem to think I'm arguing that the entire genome must be functional."

I'm glad to hear you don't think that.

"To restore context:

"The general idea from creationists is that their god would not design a genome that is MOSTLY junk."

To test this we'd need to know what God would or wouldn't do (in terms of our genome). We don't know that, so it's not a scientific claim."

I'm glad to hear that, too. You are absolutely right there.

The whole truth said...

"Along this line, it fully explains why complex mammals have much less variation in genome size relative to lower species such as fish or plants. The simple unicellular organism protozoa kind has a genome size variation range with one end ~20000 fold larger than the other end whereas mammals only less than 10 fold. The real significant question on genome size should be why the protozoa kind has such huge variation in genome size, rather than why the onion has such a huge genome."

gnomon, why do you think that mammals (All mammals or just certain ones?) are more complex than fish or plants? What justifies calling fish or plants "lower"? And why did you use the word "kind" in regard to protozoa?

Chris B said...

BC,

"You accuse me of not paying attention, but let's see what Dr. Graham actually wrote:

"It's because, over a decade after the first draft of the human genome was published, we still really don't have any idea of what most of it actually does."

And:

"I think the bottom line is that there are so very few detailed functional studies of specific regions of the genome that the topic remains open.""

At the risk of accusing you of not paying attention again, do you remember that this entire thread started with Dr. Moran's post criticizing Dr. Graham's characterization of the extent of functionality in our genome, and what science knows about it?

Anonymous said...

I feel a need to counter BC's misreading of my statement, "Knowing what's in our genome in much more detail than we know now, isn't going to lead directly to cures for cancer, Downs syndrome, cystic fibrosis, or other illnesses. It will give us good clues, but that's all."

First, this statement is not in any way an implication of evolutionary theory, though BC says it is, above. This is a generalization from observations of attempts to treat and cure genetic disorders.

Second, understanding the genetic basis of a genetic disorder such as cystic fibrosis is merely a useful first step toward treatment or cure. Other steps include understanding how the effected protein functions in the cell, how effects of the defective protein can be countered in the cell, and how (if at all) these treatments can be applied to humans. Alternatively, cure may require figuring out how to safely and effectively change DNA sequences in living humans. These steps are not trivial! Therefore, the path from knowing the genetic sequence to cure or effective treatment is not direct.

gnomon said...

Are bacteria lower than multicellular organisms? or humans? If so, the same kind of logic applies to calling fish or plants lower. It can be quantified by the number of cell types at the phenotype level and by the degree of maximum tolerated random errors at genome level.

I could use type but kind seems to cover a more wide spectrum of the same thing. That it may have other meanings associated with historical baggage is just unfortunate.

Regarding complexity, you should worry when people pursue their research with total disregard to the issue of complexity. How can one ignore a part of reality and yet expect to be able understand it? Do the junk DNA fans really believe that two humans can one day differ by 90% at the nucleotide level? Why don't they go test their ideas by asking whether cancer or Parkinson's disease patients have or have not higher genetic diversity than normal matched controls? The claim that the observed 0.1% difference in DNA between two humans is the optimum level for humans can be easily proved by testing whether patients of cancer or other complex diseases have higher level of genetic difference. Instead of uselessly arguing what does function or junk mean, the junk DNA fans should make better use of taxpayer money and go out do some actual experiments to test their assumptions and their idea's predictions. You, the whole truth, as an observer and taxpayer only interested in truth can probably organize a grassroots campaign to force them to do it (No one can easily give up self-interest). The smart ones among them will do their best to resist because they know either in good conscience or by reading my papers that they are hopelessly doomed.

The whole truth said...

gnomon, I think it's better to say that bacteria are different, not "lower" than multi-cellular organisms, including humans. I also think it's better to say that fish or plants are different, not "lower" than humans or other mammals. An argument could even be made that fish, plants, and bacteria are superior to humans and other mammals. For example, fish, plants, and bacteria have been around far longer than humans and any other mammal and they will still be around long after humans and/or other mammals are extinct.

Humans have invented various measuring standards for various things and many of the measuring standards have worthwhile uses but I'm wondering why "the number of cell types at the phenotype level" or "the degree of maximum tolerated random errors at the genome level" should be the determining standard for labeling organisms as higher or lower? I also really wish that everyone would stop calling variations or changes or mutations "errors". "[E]rrors" implies negative deviations from perfection, and nothing in nature is perfect. Some people might argue that "errors" just means deviations from 'the norm', but since evolution is always occurring then variations/changes/mutations are 'the norm'.

If humans are higher (or more complex) and bacteria are lower (or less complex), what are some examples of organisms that are the mean?

I don't understand why you think that complexity is totally disregarded/ignored by researchers, and will you please explain what you mean by this: "Do the junk DNA fans really believe that two humans can one day differ by 90% at the nucleotide level?"

You also apparently think that no one is studying DNA to find out exactly what is 'junk' and what isn't, and I don't understand why you would think that. It appears to me that many scientists are studying DNA to gain greater knowledge so I don't think that I need to organize a grassroots campaign to force anyone to do it.

gnomon said...

To an untrained nonspecialist in art or music or wine etc, things are just different and no good and bad. The drive to not to be content with just calling things different is key to advances in civilization. Without that drive, we would not have come with the concept of prime numbers (why picking out the primes when there is nothing wrong to call all numbers different) and in turn would not have to face the most fundamental mystery of humanity, the Riemann hypothesis. But then, human life would be so boring with nothing challenging to do. To organize, classify, and discover hidden patterns/orders is what science is all about. Lower is just a common sense word that can describe the situation better than any other words. It also works in solving mysterious patterns such as genetic equidistance whereas as calling species different lead us nowhere in understanding nature.
Atomic bombs could wipe out humans easily but not bacteria. But then a junkyard would have the longest lifetime expectancy. An objective, useful, and consistent standard of complexity is tolerable entropy within a system. By that standard, bacteria is more like a junkyard than a human is, and human is the least junkyard like among species on Earth.
Mutation is random, which no one seems to deny. And random is a far more destructive force than a constructive one to an ordered system, which is just common sense and easily verifiable. Evolution from simple to complex involves a gradual, constant, and stepwise suppression of randomness or entropy, which is best shown by the genetic equidistance phenomenon. Wishful thinking about what a mutation is or is not may make some people comfortable but really has no values in terms of solving mysteries.

A huge and unrealistic assumption of the modern synthesis is that complexity differences, whatever that may mean, are not important in understanding evolution. That approach has been proven false or non-productive by the fact that the genetic equidistance phenomenon has remained unsolved for nearly half of a century and the fact that the genetic diversity riddle has remained unsolved for nearly one century.
If 90% of human genome are junks or can freely mutate without effects on human reproduction, then given enough time, the genetic difference between any two humans could increase from the present 0.1% to 0.2% (the level seen in chimpanzees), to 0.3%, 0.4%, etc etc all the way to 90%.

The approach taken by the neutralists to study DNA is not realistic by the standard of science or experimentalists, to put it simply. They are too easy or non-critical on themselves and adopt unrealistic assumptions that happen to make their life easier. They publish research papers claiming 8.2% functional genomes for humans. However, the assumptions under such research are false. One is non-conservation means non function. The other is that they ASSUMED certain DNAs to be non-functional to begin with, which may sound reasonable to the less critical but no one really knows. The more correct approach is to assume nothing, which means putting aside the theorizing and just do experiments. Most of the assumptions were made half of a century or one century ago when people have few DNA sequences to work with, and hence could not be experimentally tested for technical reasons. But today things are much different and there are no more technical difficulties. Even better, there is now a competing alternative set of assumptions as in our MGD thesis. To decide which side is true is as easy as doing 1 + 1. Our side has in fact done plenty of tests already. A small part of reality is found consistent with the neutralists’ assumptions while most not. It is really not very hard at all to tell the difference between the two kinds of realities, or between linear and equilibrium. All it takes for the other side is courage to face reality.

BC said...

judmarc,

"@BC - You keep talking about shoehorning while describing its opposite."

You keep talking about explanations, whilst failing to provide them.


"Genetic load is a fact. 130 mutations per human generation on average is a fact."

I have referred to the "observed number of new mutations" many times. We know that errors occur during DNA replication.


"The "onion test" (even closely related species can vary wildly in the sizes of their genomes) is a fact."

The "onion test" is not a fact. The fact is that some organisms have much more DNA per cell than humans, whilst having less obvious developmental/cognitive complexity. Genome duplication is one explanation for this (many of the examples are polyploid organisms) and MGEs are another (see below). The "onion test" is based on the implications: that eukaryotic genomes are carrying large amounts of excess baggage. However, the fact is that the extent of this baggage in humans is currently unknown.


"Much of the human genome being composed of stuff like retrotransposons, LINEs, SINEs, etc., is a fact."

About 40% of the human genome is comprised of retrotransposons (which includes LINEs and SINEs). These are one of several types of mobile genetic elements (MGEs), so called because they can move around in the genome. There's evidence that they play a role in gene expression and regulation (even those that can no longer move), and that they contribute to genetic diversity. MGEs are also implicated in disease and aging. It's no surprise then, that the discovery of these fascinating elements earned Barbara McClintock a Nobel Prize. Some scientists claim that MGEs are mostly junk. Whilst this may be a reasonable assumption, the fact remains that only a tiny fraction have been analysed for function.


"Having pointed out yourself that any "explanation" that purports to rely on the intent of a deity is not a scientific claim, what is your scientific explanation for these facts?"

See above.

And now that you've demonstrated your ability to shift the goal posts, perhaps you'd like to address my point? You say that genetic load is a fact, and presumably you agree with Professor Moran that the number of mutations is unacceptably high. If this is the case, I've argued that significant amounts of junk are required to make the facts fit the evolutionary narrative. If the amount of junk is not important, how do you resolve this anomaly?

BC said...

Chris,

"No. The mutation rate has been independently measured many different times using several different methods. They all vary, of course, but generally fall in the same order of magnitude. That is called empirical data, and it poses no problem whatsoever for evolutionary theory, or genetics, or cell biology, or physiology, or..."

Except that:

"If the majority of the genome was constrained by sequence, this would be an unacceptably high mutation rate."

So, without a significant amount of junk the empirical data does indeed pose a problem for evolutionary theory (an unacceptably high mutation rate). It seems we now agree on this.


"Please don't point to 'once perfect' and use that to weasel out of your absurd claims. We could just as well say 'more perfect' and the argument remains unchanged. You silly alternative of 'the fall' and the rest of your theology is a fairy tale with no evidence whatsoever to support it. So yeah, that's shoehorning your religious beliefs into reality."

Changing your argument to say "more perfect" is of no consequence. We don't know whether the original condition was "once perfect" or "more perfect" or whatever you want to change it to. There's no shoehorning necessary.


"I'm not conflating evidence with assumptions. I think that broken genes, broken transposable elements and broken fragments of viral DNA integrated into our genome are not essential functional elements. Is that unreasonable?"

You're doing it again! We don't yet know whether the majority of the genome is broken. It is not unreasonable to assume that, but it is unreasonable to complain about people that express another opinion and want to do further research. Especially if the reason for doing so is to support your pet theory.


"You clain function has been been demonstrated for these elements "many times". What percentage of our genome has been proven functional in this way? I'm not saying it is impossible for these elements to acquire a function, how often has this actually happened? What do the scientific studies tell us, BC?"

It's a very small percentage, and it's certainly not happening every day. But that's to be expected, because the scientific studies tell us that (for the time being at least) the functional analysis is very difficult.


"The genetic load argument remains important for anyone interested in genome function, not just this blog."

I didn't suggest otherwise. My point was that it's important to this blog because the genetic load argument (without significant junk) refutes the brand of evolutionary theory advocated here.


"At the risk of accusing you of not paying attention again, do you remember that this entire thread started with Dr. Moran's post criticizing Dr. Graham's characterization of the extent of functionality in our genome, and what science knows about it?"

Of course, and you raise the important question: what does science know about it?

On the one hand, there are scientists that make the assumption that most of our genome is junk. Other scientists assume the opposite (and both have reasons for doing so). But Professor Moran and those he counts as "knowledgeable scientists" are vehemently against the latter. Could it be because function would refute the version of evolutionary theory he holds to? That would seem to be the case, so it's ironic that he followed this post with one in which he makes accusations of "confirmation bias".

BC said...

bwilson295,

"First, this statement is not in any way an implication of evolutionary theory, though BC says it is, above. This is a generalization from observations of attempts to treat and cure genetic disorders."

Oh really? You prefaced your statement about "knowing what's in our genome" with the following:

"But we do know what most of the genome is; dead transposons, dead viruses, mRNA read back into the DNA, and remnants of old duplicated genes that mutated away from function."

As I said, evolutionists love "we know most things, we're just sorting out the details". Yours is a potentially dangerous assumption, and Dr. Graham disagrees with your assessment:

"[P]ersonally I think the bottom line is that there are so very few detailed functional studies of specific regions of the genome that the topic remains open."

Don't let your evolutionary bias get in the way. More details are a good thing.


"Second, understanding the genetic basis of a genetic disorder such as cystic fibrosis is merely a useful first step toward treatment or cure. Other steps include understanding how the effected protein functions in the cell, how effects of the defective protein can be countered in the cell, and how (if at all) these treatments can be applied to humans. Alternatively, cure may require figuring out how to safely and effectively change DNA sequences in living humans. These steps are not trivial! Therefore, the path from knowing the genetic sequence to cure or effective treatment is not direct."

All the steps you describe here would contribute to "knowing what's in our genome". If you meant "knowing the genetic sequence", perhaps that's what you should have written.

And with that, I'd like to thank you all for an interesting discussion. I hope that at least some readers appreciated the point I was trying to make.

Chris B said...

"So, without a significant amount of junk the empirical data does indeed pose a problem for evolutionary theory (an unacceptably high mutation rate). It seems we now agree on this."

No it does not. I do not agree with you.

Since previous attempts to explain this have been met by you with chicken and the egg arguments, let's try another approach. Let's say your dreams come true, and most of the genome is functional, despite our terrible "fall" which doomed our genome to inexorable degeneration, and mysteriously affected all other living creatures on the Earth as well, who apparently were also booted out of the garden of eden.

The empirically determined mutation rates you agree with happen. So in order for all those broken transposable elements, broken bits of viruses, pseudogenes, etc. to be functional, their functionality would have to be independent of sequence. Or at least functionality would be resilient in the face of mutational changes. If this were really the case, we would have discovered something previously unknown about the human genome:

1. all of that repetitive and broken down stuff performs vital functions, and
2. does so with little or no contribution from the actual nucleotide sequence.

This would indeed change our understanding of how the genome works, and lead to entirely new avenues of scientific research.

Claiming that this would disprove evolutionary theory or even be a problem for evolutionary theory is absurd. That would be like saying if we found a new hormone that affects sugar metabolism that all we knew about insulin, the pancreas, its affect on blood circulation and peripheral nerve sensation has all been disproven. It's a big problem for physiology!

Chris B said...

BC,

"Changing your argument to say "more perfect" is of no consequence."

Yes, that's what I said and that was my point. Glad that you got it.

"We don't know whether the original condition was "once perfect" or "more perfect" or whatever you want to change it to. There's no shoehorning necessary."

We can change it to whatever you can dream up.Saying some amount of 'junk' in our genome is a result of the 'fall' is a non-scientific fairy tale. And you have zero (0) evidence to support it. Is that finally clear yet?

Chris B said...

BC,

"You're doing it again! We don't yet know whether the majority of the genome is broken. It is not unreasonable to assume that, but it is unreasonable to complain about people that express another opinion and want to do further research. Especially if the reason for doing so is to support your pet theory."

No, I'm not doing it again. I never did it in the first place. I said quite plainly that it is perfectly plausible that we might find functionality for these huge parts of the genome that have no known function. So far it has not been for a lack of looking. The instances of discovered functionality have been rare, but very interesting, and if anything demonstrate the contingency and opportunistic tinkering that evolutionary theory would predict. I'm all for continuing the search. The more functional elements we discover, the more we know about how the genome works and the more we can do to understand genetic diseases. Sequencing has shoen that most of it looks like broken transposons, pseudogenes, repetitive elements and pseudogenes. Some tiny fraction of these has been shown to have been co-opted for some function. The burden of proof is on demonstrating functionality.

"It's a very small percentage, and it's certainly not happening every day. But that's to be expected, because the scientific studies tell us that (for the time being at least) the functional analysis is very difficult."

Yes it is. So in the mean time, I'll leave you with two thoughts. First, to use this lack of knowledge as an argument is an argument from ignorance. To scientists, such mysteries are areas to be investigated, not areas conceded to "the unknown". You can't hide behind ignorance forever. Second, when the answers to the function or lack thereof, of parts of our genome are found, it will be done by scientists. It will not be done by ID/creationist bloggers or Discovery Institute posers. And for the reasons I explained above, regardless of the outcome, it will not refute evolutionary theory.

Schenck said...

Larry Moran:
"You are telling your audience that some scientists believe that all noncoding DNA is junk—this is false—and you hope to prove that it is not junk."

That's a fairly uncharitable reading of what was written, and I would think that you've arrived at that reading because you are primed to.
Explaining that we don't have personalized medicine yet because it isn't obvious what the mutations that are associated with diseases are actually doing does not mean "Whoa everyone thought this DNA was junk but there's like, totally a purpose for it, we are revolutionaries"|

I agree, a person, whether a layperson or an established authority onthe topic, COULD misread Dr. Graham's statement like that, and yes it would've been better if she'd gotten into the nitty gritty. OTOH I don't write science for popular consumption, so I'm a little bit wary of telling someone who does it and does it well, while also maintaining a good research program, how they should go about doing that.

Schenck said...

Beau Stoddard:
"why is the junk DNA topic so hot?"
It's not.

"How is it harmful to search for purpose in what has been labeled junk?"
It's not.

" I guess i don't understand the end game here."
Dr. Moran is making a very valid argument and important point about how "Junk DNA" has, somehow, become misunderstood and misused even in the molecular and evolutionary biology community.
I disagree that this article cited is somehow the result of ignorance on the part of Dr. Graham, or that she was really trying to say " lol wut Junk DNA lol no we're discovering it has functions *takes a selfie*"

Faizal Ali said...

I agree, a person, whether a layperson or an established authority onthe topic, COULD misread Dr. Graham's statement like that, and yes it would've been better if she'd gotten into the nitty gritty.

Such an interpretation would not be a "misreading". That some scientists have believed all non-coding DNA is junk is is the only correct interpretation of what she wrote:

In fact, genes make up only 2% of the human genome, with the remaining 98% often dismissed as “junk” DNA.

Can you give another valid interpretation of that sentence? The only possibility I can see is that, when she refers those who dismiss it as junk, she is talking only about non-scientists. But that would be splitting hairs very finely, and I doubt that is what she meant to convey. There is no reason she could not have made an accurate statement like "...with much (some say most) of the remaining 98% comprising 'junk'. The interesting question that is the subject of much investigation is: 'What functions are performed by the parts of the genome that are non-coding, but which are also not junk?'"

I think any layperson should be able to understand that. Don't you?

Schenck said...

She said: "we hope to add functionality to the DNA sequence information, and try to work out what that 98% of junk DNA actually does and how it contributes to disease progression."
This does not mean "all non-coding DNA is junk", that is a misreading, and a fairly uncharitable one given that she works on the subject. I SUSPECT she knows what regulating sequences are.

"Can you give another valid interpretation of that sentence?"
Are you saying the remaining 98% is NOT often dismissed as "junk"??? Her summary is perfectly fair. Yes, the non-gene coding part of DNA is not all functionless. She did not claim that non-gene coding DNA is functionless.
Are you honestly this upset at "She shouda said 'much' not most'?? THe only way she could say 'most' instead of 'much' is if she's an idiot or a liar?
That's ridiculous.

Faizal Ali said...

This does not mean "all non-coding DNA is junk", that is a misreading, and a fairly uncharitable one given that she works on the subject. I SUSPECT she knows what regulating sequences are.

That is not in question. The issue is her misrepresentation of what others in the field say.

Are you saying the remaining 98% is NOT often dismissed as "junk"???

Yes, that is exactly what I am saying. If I am wrong, please correct me by citing examples of people who have made that claim.

Schenck said...

"The issue is her misrepresentation of what others in the field say."
She hasn't misrepresented anyone, that's a heckuva accusation to make. The 'remaining 98%' is often dismissed as "junk". Correct, it's not dismissed as junk by many molecular biologists. This is a perfectly legitimate statement that I've heard many people on this blog make before. Yes, it's erroneously dismissed as "junk". And equally, YES, many of the mutations related to disease are in the non-coding part of DNA, which makes it much harder to work with than if it were simply mutations in well understood gene coding portions.

I agree that Dr. Moran is perfectly right and justified in saying "hey hey, lets be clear about Junk DNA here, it's often misunderstood". But that's not the same as 'wow, this dumb girl is either a liar or an idiot'.

Faizal Ali said...

So no examples? Why not, if such claims are so common?

I agree that it is very common for people to claim that scientists have dismissed all non-coding DNA as junk. But I hope I don't have to explain to you that this is not the same thing as actually claiming it all to be junk. And the fact that this accusation is often made be creationists as part of their attempts to promote scientific ignorance makes it all the more unfortunate that Bryony Graham would reinforce this misconception.

Larry Moran said...

@Robert Schenck

Bryony Graham said,

It’s because, over a decade after the first draft of the human genome was published, we still really don’t have any idea of what most of it actually does.

I think that's a very misleading statement. Some of us think that 90% of our genome is junk. We could never write such a statement because: (a) we have concluded that most of the genome doesn't "do" anything so there's no mystery, (b) we know a great deal about the sequences in most of our genome so we know that most of it looks like junk.

Do you really think that people like me would ever write something like that in an article intended for general readers?

Here's what I would say ....

Long before the publication of the human genome sequence it was recognized that most of our genome was composed of junk DNA. Junk DNA has no biological function. Now that we know the sequences of many human genomes this conclusion has been confirmed. About 90% of our genome is junk.

The remaining 10% contains a multitude of functions including genes that encode proteins, structural sequences like centromeres, genes for functional RNAs that don't encode proteins, sequences involved in copying DNA, and regulatory sequences that control the expression of genes. There are many other types of functional sequences that we don't have room to describe here.

Many of the mutations that cause cancers and other genetic diseases are not found in the 2% of the genome devoted to protein-coding genes as some workers might have expected fifty years ago. Instead, those mutations are localized to the regulatory sequences and other functional parts of the genome which make up four or five times the amount of DNA devoted to protein-coding genes.

In addition, some of those mutations are located in junk DNA, converting functionless DNA to new sequences that interfere with normal cell metabolism.


What's wrong with that? Isn't it legitimate to ask why someone who understands junk DNA wouldn't have written such an accurate description of the current state of knowledge?