Saturday, March 21, 2015

Junk DNA comments in the New York Times Magazine

It's always fun to be quoted in The New York Times Magazine but there's a more serious issue to discuss. I'm referring to a brief article about online comments after Carl Zimmer published a piece on "Is Most of Our DNA Garbage?" a few weeks ago. If you read the comments under that article you'll discover that we have a lot of work to do if we are going to convince the general public that our genome is full of junk.

The most common approach was from commenters who thought that junk DNA was just a term to describe our ignorance of what's in the genome. They believe that scientists know very little about genomes and that's why they came up with the junk DNA concept. Words like "hubris" and "arrogance" are thrown about.

This is a problem because it indicates a mistrust of scientists and a misunderstanding of how science works. But in fairness, there are a good number SCIENTISTS who also think that there's no evidence for junk DNA.

The other common misconception was that evolution (i.e. natural selection) is so powerful that any real junk DNA would have been eliminated by now. This is also a slap at scientists because in order to make this argument you have to claim that Ryan Gregory and other junk DNA proponents know nothing about evolution. The irony is that the proponents of junk DNA seem to be far more knowledgeable about evolution than those who oppose junk DNA.

Here's the article about the comments: Re: Is Most of Our DNA Garbage?.
Is there garbage in our genome? Carl Zimmer’s March 8 article about the debate in the scientific community over junk DNA sparked a conversation that spread to the blogs of half a dozen scientists.
It's true that many of us commented on Carl's article but it's also true that Carl's article was, in part, prompted by science blogs. This is a debate that's been taking place on the internet for 25 years.

For the most part, the comment on comments makes reference to supporters of junk DNA. That's good.

The photo below shows Carl Zimmer having lunch with three science bloggers last December [Is most of our DNA garbage?].



Image Credit: The cartoon is by Tom Gauld and it was published online at the The New York Times Magazine website. I hope they will consider it fair use on an educational blog.

121 comments :

  1. @ Laurence A. Moran,

    It has been clear for decades now that in organisms with high C-value, such as humans, most genomic sequences *CANNOT* have informational functions because of the following fundamental knowledge in the field of genome biology and evolution:

    (i) C-value paradox or enigma;
    (ii) Mutational load;
    (iii) Evolutionary origin of most genomic sequences from transposable elements;
    (iv) Essential requirement for some ‘structural’ or ‘spacing’ DNA sequences implicated in gene expression and genome architecture;
    (v) Limited sequence conservation in most genomic regions between evolutionary related species.

    The ENCODE leaders knew this, and you know this, but because both of you have a hidden agenda, you continue to pretend this knowledge doesn't exist.

    I already revealed ENCODE’s hidden agenda ( http://www.ncbi.nlm.nih.gov/pubmed/23479647). Here is shot at your hidden agenda.

    As I pointed out before (see link above), the fundamental scientific question remaining about the biology and evolution of the so called “junk DNA” (jDNA), is whether jDNA has non-informational functions, or not.

    However, you don’t want to focus on this relevant scientific question, because you are afraid that answer might be that jDNA if functional, so you muddy your blog with misleading issues and questions distracting from it.

    ReplyDelete
    Replies
    1. There is DNA in our genome that is not conserved but it has a function. I've discussed this many times. The best examples are spacer DNA between transcription binding sites and the minimum length of introns.

      That DNA is not junk by any definition that I think is valid. Others disagree with my definition.

      The question you keep harping about is whether there is a huge amount of functional DNA that doesn't have conserved sequence. You seem to be more interested in quibbling about definitions than in presenting your case for such functions.

      For the record, one last time, if any of the bulk DNA hypotheses are correct then that DNA has a function and it isn't junk DNA.

      If you persist in misrepresenting my views on my own blog, I'm going to ban you. I'm rapidly losing patience. You are acting like a kook and you no longer deserve respect.

      Delete
    2. Laurence A. Moran says: “For the record, one last time, if any of the bulk DNA hypotheses are correct then that DNA has a function and it isn't junk DNA”

      We agree on that. Then, why not *focus* on these hypotheses when addressing the evolution of genome size and the potential functions of the so called “junk DNA”, which I prefer to call “symbiotic DNA”?

      From a scientific perspective, these hypotheses should be at the center of the discussion when addressing the evolution genome size and potential biological functions for symbiotic DNA.

      Delete
    3. I don't focus on the bulk DNA hypotheses because they are NOT at the center of the discussion and because none of them make any sense. If any serious scientists start to push those explanations then I'll take the time to show why they are wrong.

      Right now, we have enough trouble convincing scientists that the other speculations about function are false.

      Delete
    4. Larry, to clarify the definitions, would "spacer DNA between transcription binding sites and the minimum length of introns" constitute bulk DNA in a small sense (I.e. we need hundreds of base pairs), as opposed to bulk DNA in a large sense (I.e. we need billions of base pairs)? Is it OK to talk about micro-bulk vs. macro-bulk, or is bulk of any kind illogical?

      Delete
    5. Laurence A. Moran says: “I don't focus on the bulk DNA hypotheses because they are NOT at the center of the discussion and because none of them make any sense. If any serious scientists start to push those explanations then I'll take the time to show why they are wrong.”

      Well, the bulk DNA hypotheses might not make sense to you, but they make sense to other people. For example, have you taken time to address the “RNA antibody” theory by your compatriot Donald Forsdyke, who is an Emeritus Professor and author of a popular book “Evolutionary Bioinformatics”? What do you think about his theory?

      Also, I think it would be highly relevant to have people such as Cavalier-Smith, "PZ" Myers, Ryan Gregory, Ford Doolittle, Carl Zimmer, who have written extensively on the evolution of genome size, state here at Sandwalk that indeed none of the so called “DNA-bulk hypotheses” make any sense ?

      It is unlikely that all of them will respond, but at least your friends Ryan Gregory and Carl Zimmer, who are featured in this post and in the New York Times Magazine, should openly support your idea that none of the bulk DNA hypotheses make any sense, if they indeed believe that.

      Delete
    6. Claudiu Bandea,

      I think it is about time you spill your guts out about what you think jDAN is for and how it applies to evolution.

      Delete
    7. Hi Pest,

      I already did it, perhaps too many times here at Sandwalk, but you are welcome to read my paper and ask specific questions; you can find it at: http://biorxiv.org/content/early/2013/11/18/000588

      Delete
    8. Just to clarify, the discussion here is not if *some* (e.g. a few percentages) of the “symbiotic DNA” (also called “junk DNA”) is functional or not; the answer to this question is clear: yes.

      The question that has remained unanswered for half of century is whether *all* or *most* of this symbiotic DNA is functional or not.

      Delete
    9. Larry, to clarify the definitions, would "spacer DNA between transcription binding sites and the minimum length of introns" constitute bulk DNA in a small sense ...

      Yes. I use "bulk DNA" to refer to any DNA that just there to provide extra space in the genome without regard to sequence. There's no question that some of the DNA in a genome serves this function. Probably less than 1%.

      Delete
    10. Claudiu Bandea,

      Before you do get banned, I would like to ask you few questions;
      1. Graur and Larry believe that if 90% of our genome wasn't junk, the genetic load would be too high. Graur claims that if ENCODE is right then we should have 7x10^45 children. So do you agree or disagree with any of those statements?
      2. If you are right about your THEORY, what is the mechanism of evolution?

      Delete
    11. @Pest

      The genetic load argument doesn't apply to bulk DNA functions because the sequence is irrelevant.

      Delete
    12. Pest,

      As Larry mentioned, the genetic load argument only applies to informational DNA (iDNA); it does not apply to non-informational DNA (niDNA).

      As a matter of fact, none of the other arguments I listed in my first comment on this thread (the one that infuriated Larry) apply to the putative functions of niDNA.

      So, according to my theory, niDNA, which represent more than 90% of the human genome, is functional. But there are other theories out there, which are well recognized in the field of genome biology and evolution. Take for example the recent statement by Ford Doolittle in his PNAS article ( http://www.ncbi.nlm.nih.gov/pubmed/23479647):

      Cavalier-Smith (13, 20) called DNA’s structural and cell biological roles “nucleoskeletal,” considering C-value to be optimized by organism-level natural selection (13, 20). Gregory, now the principal C-value theorist, embraces a more “pluralistic, hierarchical approach” to what he calls “nucleotypic” function (11, 12, 17)”

      About Dan Graur’s claim, I’m not sure, because the material explaining the claim doesn’t seem to be available; apparently, the link is non-functional, in other words it's “junk”.

      Regarding my theory, it explains the evolution of genome size and the C-value paradox or enigma.

      Delete
    13. Here is the summary of Graur's Post:

      "Dan Graur has written a good summary of genetic load. It’s an important concept in population genetics, and everyone should be familiar with it…and this is a nice 2½ page summary with only a little math in it.

      I’ll try to summarize the summary in two paragraphs and even less math … but you should read the whole thing.


      Genetic load is the cost of natural selection. You all understand natural selection (my usual problem is trying to explain that there’s more to evolution than just selection), and so you know that you can’t have selection without imposing a loss of fitness on individuals that lack the trait in question. As it turns out, when you do the math, the only parameter that matters is the mutation rate, µ, and the mean fitness of a population, w, is (1-µ)n, where n is the number of loci, or genes, in the genome. What w is, basically, is the cost to the population of carrying suboptimal variants.

      Notice that (1-µ) is taken to the nth power — that tells you right away that the number of genes has a significant effect on the cost to a population. As Graur shows by example, using a reasonable estimate of the number of genes and the mutation rate, the human genetic load is easily bearable — if each couple has about 2½ children, losses due to selection overall will be easily compensated for, and the population size will be stable. But if n is significantly greater than 20-30,000 genes, because of that exponent, the cost becomes excessive. If the genome was 80% functional, he estimates we’d each have to have 7 x 1045 children just to maintain our current population.

      What all this means is that there is an upper bound to the number of genes we can possibly carry, and it happens to be in the neighborhood of the number of genes estimated in the human genome project. We can’t have significantly more, or the likelihood of genes breaking down with our current mutation rate would mean that most of our children would be born dead of lethal genetic errors, or the burden of a swarm of small deficits to their fitness.

      What Graur doesn’t mention is that this is old news. The concept was worked out in the 1930s by Haldane; it was dubbed “genetic load” in 1950 by Muller; Dobzhansky and Crow wrote papers on the topic in the 50s and 60s. I learned it as an undergraduate biology student in the 1970s. I have an expectation that more advanced and active researchers in the field will have this concept well in hand, and are completely familiar with it. It’s just part of the quantitative foundation of evolutionary biology.

      And this is why some of us go all spluttery and cross-eyed at any mention of the ENCODE project. They just blithely postulated orders of magnitude more functioning elements in the genome than could be tolerated by any calculation of the genetic load — it quickly became clear that these people had no understanding of the foundation of modern evolutionary biology.

      It was embarrassing. It was like seeing a grown-up reveal that he didn’t know how to use fractions. It’s as if NASA engineers plotted a moon launch while forgetting the exponent “2” in F= gm1m2/r2. Oops.

      When well-established, 80 year old scientific principles set an upper bound on the number of genes in your data set, and you go sailing off beyond that, at the very least you don’t get to just ignore the fact that you’re flouting all that science. You’d better be able to explain how you can break that limit."

      Delete
    14. Correction: 7 x 10^45 children

      Delete
  2. You know, it might help to pitch the genetic load argument in a way that shows that the junk is good for something after all: keeping deleterious mutations manageable. You may not like that pitch because it is adaptationist, but if it serves to get people to accept reality...

    ReplyDelete
    Replies
    1. I don't follow your argument. How would telling a lie get people to accept reality?

      Delete
    2. How can it be a lie if we don't even know what it means? I for one have no clue what "keeping deleterious mutations manageable" is intended to convey.

      Delete
    3. Ah. I have thought this through a bit more and realise that I probably misunderstood the situation. I guess if our genome did not have any junk at all, only 100% coding regions, then the rate of deleterious mutations would also be low enough for us to survive? The high number discussed here is only so high because our genome is so large, and of course without junk it wouldn't be, and thus the number of mutations would be smaller. And this would then be low enough?

      Bear with me, it is after midnight here and I should go to bed...

      Delete
    4. The number of mutations is directly proportional to the size of the genome. The number of mutations in functional regions of the genome does not depend in any way on the amount of junk in the genome.

      Delete
    5. John,

      Can you define what "mutations" you are you talking about?

      Delete
    6. Just to be clear: when you say “mutations’ in your statement above, you do not include mutations by inserting elements, such as transposons or retroviruses, do you?

      Delete
    7. @AlexAh. I have thought this through a bit more and realise that I probably misunderstood the situation. I guess if our genome did not have any junk at all, only 100% coding regions, then the rate of deleterious mutations would also be low enough for us to survive?
      Why would you write that? It presses the entirely bogus view that junk DNA means non-coding DNA. Presumably you know better but some very public comments others have made, and keep making, suggests that it's a very common misunderstanding. Please apologize and make restitution by correcting 100 others who say such a sloppy thing.

      Delete
    8. @Claudiu,
      If I see where you're going, if the number of events of a transposable element inserting itself is constant, then decoy DNA reduces the chance of an insertion in a "functional" region. Of course, if there's lots of decoy DNA, more transposable elements can be tolerated so the numbers build and there will be a higher frequency of insertion events. So isn't it a wash? A small genome that gets some knock outs means those individual mutants suffer the consequences. So what, we'll make more.

      Delete
    9. Roger,

      Your make a good point, but please read the paper to better understand all the evidence and arguments for my theory ( http://biorxiv.org/content/early/2013/11/18/000588).

      Indeed, you would l think that if organisms, such as Bacteria for example, have a small genomes and a high rate of reproduction, they would not be affected by deleterious insertional mutagenesis. Surprisingly though, that is not the case, as in these organisms, the selection pressure against insertional mutagenesis and, I should add against large genomes, is so strong that many of these inserting elements (e.g. transposons, lysogenic phages) and their hosts have co-evolved specific genomic sites for integration.

      Delete
    10. I wouldn't think that. I would think that for bacteria, especially fast growing bacteria, that the time spent replicating their DNA can be a limiting factor that selects against expanding genomes. There's also likely a few orders of magnitude difference in cellular energy budget spent on DNA replication.
      And again, tossing in jDNA to increase the tolerance against insertional mutagenesis just winds up supporting more active transposable elements returning to the prior risk of insertion in functional DNA. If you can write a paper that's mostly speculation about what you think happens, I can return the favor in the comment section of a blog. Neither of us has provided a useful mathematical model. If you did, you might realize that jDNA to protect against insertion induction of cancer is a red herring. That's my last word.

      Delete
    11. Obviously Roger, you are entitled to your opinion, and we respect that here at Sandwalk.

      Delete
    12. roger shrubber,

      Something like decoy DNA was what I was thinking of above. But I hope you are joking with your first comment responding to me: of course junk DNA is non-coding in the sense that it doesn't code for anything the organism couldn't do without. That's the whole point of the concept.

      Delete
    13. @roger

      It takes about 40 minutes to replicate the E. coli chromosome. The bacteria divide about once every 24 hours in the wild. Genome size is not limiting under those circumstances.

      However, in the laboratory under ideal growth conditions the generation time can be 30 minutes or even a bit less. Clearly E. coli have evolved a mechanism for growing and dividing faster than the time it takes to replicate a single chromosome from start to finish. Thus, genome size isn't limiting even when they are dividing as fast as possible.

      How they do this used to be a favorite exam question but I bet very few of today's undergraduates could come up with the answer.

      Delete
    14. Alex, I am not joking. If you call junk DNA non-coding DNA, you are asserting that any DNA that does not code for protein (or rRNA, tRNA) is junk. That was _not_ the original definition of junk DNA. Only very sloppy language has promoted that idea. But that idea has surfaced where people point to regulatory sequences as examples of how non-coding DNA is not junk, thinking they have dispoven the concept of junk DNA.
      Sorry to be rude but don't be dense. Junk DNA does not, and never has, meant non-coding DNA. Sure, coding DNA is not junk. But don't promote an insipid false dichotomy where you then think that non-coding DNA is therefore junk. I double your penance because you've shown yourself to be part of the problem.

      Delete
    15. "How they do this used to be a favorite exam question but I bet very few of today's undergraduates could come up with the answer."

      Hmm, I don't actually know the answer to that but my I'll take a stab at it. I guess they start making new copies of their chromosome before the previous one is finished. Is that correct?

      Delete
    16. Larry, I'm willing to be educated. My bear of very little brain says that bacteria that reproduce faster than it takes to copy their genomes inherit partially replicated genomes. However, that is a limiting proposition. Double that genome size and you will slow the rate of replication.
      Average rates of replication are not necessarily the right metric. Times of rapid replication matter more, that's a consequence of the maths of exponential growth.
      Ultimately, the maths matters and there's some ambiguity about the boundary conditions, as far as I know, which isn't very far. But I'm willing to learn with a decent nudge.

      Delete
    17. roger shrubber,

      Your language is indeed unnecessarily rude and insulting.

      I maintain that the word junk, by its definition, must mean something that the organism could do without, and thus "doesn't code for anything the organism couldn't do without" fits. It may code for parasitic DNA of some kind, but if it codes for something that is necessary for the functioning of the host cell then it quite simply isn't junk.

      Delete
    18. Hmm, I don't actually know the answer to that but my I'll take a stab at it. I guess they start making new copies of their chromosome before the previous one is finished. Is that correct?

      I would imagine that is the answer Larry is looking for. Thus, during rapid growth, and with respect to the genes proximal to the origin at least, the copy number of these genes will not be one or two per cell, but four at least. Perhaps this is why genes required for initiation, like dnaA and gyrA are usually located proximal to the origin - gene dosage effects, though there may be other reasons.

      Delete
    19. DNA Replication in E. coli: The Problem

      DNA Replication in E. coli: The Solution

      We used to teach the fundamental principles and concepts of information flow (DNA replication, transcription, translation) from a prokaryote perspective. There were historical reasons for this but the strategy persisted long after we began to understand these processes in eukaryotes. The processes are more simple in bacteria and still better understood.

      Most of the major textbooks are still organized like that but very few instructors in biochemistry molecular biology follow that strategy. Nowadays, they jump right into eukaryotes as fast as possible. What this means is that modern students are often overwhelmed with detail. It's a lot harder to understand translation if you have to memorize a dozen initiation factors, for example.

      I was talking to some of our very best fourth year students last week and asked them if they could explain the differences, if any, between transcription initiation in bacteria and eukaryotes. They couldn't.

      I talked to another student who was convinced that DNA replication is much more error prone in bacteria because the bacterial replication complexes don't do proofreading. She says that this is what she was taught in class. (Proofreading was discovered in bacteria.)

      I don't know why that happened. Why did lecturers abandon prokaryotes?

      Delete
    20. roger shribber says,

      Sorry to be rude but don't be dense. Junk DNA does not, and never has, meant non-coding DNA. Sure, coding DNA is not junk.

      I strongly agree with you about the use of noncoding DNA.

      However, just to make things even more confusing for the IDiots, it's not true that all coding DNA is functional (not junk).

      There are pseudogenes that have lost their promoters and can't be transcribed. Their coding regions may be intact but they are still junk. (And will eventually degrade.)

      Furthermore, there are pseudogenes that are still transcribed and translated but their proteins have lost any function. They may even be truncated. Those coding regions are junk even if they encode a protein.

      The situation with active transposons is ambivalent. They encode a reverse transcriptase that is perfectly functional and it is expressed from time to time. Some junk DNA proponents refer to active transposons as junk even though they carry a functional coding region. (I'm not one of them.)

      The way around this is to divide the genome into "functional" and "nonfunctional" regions and avoid the use of "coding" and "noncoding" altogether in the junk DNA debate.

      Delete
    21. @Alex, "coding DNA" is a term that means protein encoding DNA. You know, the part that maps nucleotides to proteins through the Genetic Code. Exons and not introns.
      That's how people read it. You seem to think it means something entirely different. You seem to think "code" means something like computer software. It doesn't. Your idiosyncratic usage is thus a recipe for miscommunication. Getting it right matters.

      Delete
    22. I don't know why that happened. Why did lecturers abandon prokaryotes?

      I am fortunately not on record saying that, but I did in fact use to say it when I was an undergraduate "who cares about yeast, give us mammals" when we were taught these processes using yeast as example (not even prokaryotes). Now I know better but this illustrates the reason - if you ask students why they're studying biochemistry/molecular/cellular biology, most will be either premeds or they want to go into research and study cancer, stem cells, neuro stuff, those kinds of things. If that's how you approach things prokaryotes are indeed irrelevant to you.

      The other problem is who is teaching. It shouldn't be that way but it's fact of life that professors tend to teach the things they do research on. Thus the changes in the composition of the faculty driven by what's hot an fundable are the other place to look for the factors responsible for this situation

      Delete
    23. Laurence A. Moran says: “The way around this is to divide the genome into "functional" and "nonfunctional" regions and avoid the use of "coding" and "noncoding" altogether in the junk DNA debate.

      I fully agree with this statement (and that’s not because Larry threatened to ban me).

      The functional DNA (fDNA) can be further divided into informational DNA (iDNA), who’s function is based on the nucleotide sequence, and non-informational DNA (niDNA), who’s function is sequence-nonspecific.

      However, I think Alex used the word “code” metaphorically to refer to the DNA that “the organism couldn't do without”, which would be the equivalent of fDNA.

      BTW Larry, can you please explain your statement: “The controversy over junk DNA is still a legitimate scientific controversy. There are some good arguments on both sides”?

      Delete
    24. Larry (or some one else who knows), did I get that answer correct in my previous post?

      Delete
    25. roger shrubber,

      Ye gods. I considered it obvious that "coding" includes coding for RNAs, and that the promoter regions and suchlike that are a necessary part of the system are implicitly included. The point is simply that junk DNA is unnecessary DNA, otherwise the word doesn't make sense. I am sure if somebody would monitor your language as closely they could also find reason to aggressively condescend towards you for being imprecise about something.

      Delete
    26. Claudiu Bandea pretends he is clueless and asks,

      BTW Larry, can you please explain your statement: “The controversy over junk DNA is still a legitimate scientific controversy. There are some good arguments on both sides”?

      There are real scientists on both sides of the issue and right now there's no overwhelming consensus on whether most of our genome is junk or not.

      That's not the case with issues like evolution vs creationism and whether global climate change is caused by humans.

      Surely you knew that?

      When I say that there are good arguments on both sides I'm simply acknowledging that not everything the anti-junk side says is ridiculous. (Just most of what they say.)

      I think you knew that too.

      So, what was the point of your question?

      Delete
    27. Mikkel,

      Sort of. What they do is start the replication at multiple spots in the chromosome simultaneously.

      Delete
    28. Alex,

      Your problem is that promoters and any other sequence that doesn't end up being transcribed into either mature mRNA or some other structural or functional RNA is *not* coding DNA.

      Delete
    29. I KNOW.

      But isn't it kind of glaringly obvious when my real point is that junk DNA means unnecessary DNA that I include everything necessary into the non-junk?

      If I said, "the cover is not the important part of a book, really what is important is what you read", would you assume I only mean the ink, because strictly speaking the paper carrying the ink isn't what you read? And would I deserve to be called dense for not specifying that you couldn't read the ink without also having the paper?

      Again: ye gods. Way to completely miss and derail the point of what I was trying to ask about mutational load.

      Delete
    30. Laurence A. Moran says: ”Claudiu Bandea pretends he is clueless and asks…”

      Well, your statement, the way I understood it, didn't make sense, so I wanted to get some input from other readers.

      This is what I wrote when I first ask for explanations (see below): The reason I ask is that, to my knowledge, the legitimate scientific controversy is whether *most* of the so called “junk DNA” is functional, or whether *most* of this DNA is not functional. But, I’m not sure what are the “*good arguments* on both sides"?

      So, what are the “good arguments” for the side saying that most of the human genome if functional? Give us some.

      Delete
    31. John Harshman: “The number of mutations is directly proportional to the size of the genome. The number of mutations in functional regions of the genome does not depend in any way on the amount of junk in the genome”

      John,

      Can you define what "mutations" you are you talking about?

      When you say “mutations" in your statement above, you do not include mutations by inserting elements, such as transposons or retroviruses, do you?

      Delete
    32. No. The number of transposon insertions is directly proportional to the number of active transposons, which is in many cases much like genome size. I'm not sure what the number of retroviral insertions is proportional to, but certainly not genome size. Still, I'd say that the number of retroviral insertion fixations is probably proportional to the number of neutral insertion sites, which probably does have something to do with genome size.

      I think you're playing games here, and I don't think you quite understand your own game.

      Delete
    33. Alex,

      All you have to do is use terminology correctly and nobody will be confused about what your point is. Well, other than the creationists. "Code for" has a meaning, and you ignore meanings at the peril of confusion.

      Delete
    34. John Harshman wrote: Sort of. What they do is start the replication at multiple spots in the chromosome simultaneously.

      I don't think that is correct. You are thinking of eukaryotic chromosomes. Bacterial chromosomes usually contain only one origin of replication (there can be exceptions of course). Mikkel is correct that they initiate new rounds of replication before the first is complete. This means that, during rapid growth, newly divided daughter cells inherit chromosomes that are already partially replicated. And the new oriC in the daughter strands of the partially replicated chromosome they inherit may themselves already be undergoing the initiation of replication. So basically, successive rounds of initiation from a unique origin before preceeding rounds of replication are complete.

      Delete
    35. SRM: I stand corrected. It turns out I was thinking of Archaea. There are suspected bacteria with multiple origins of replication, but I could find no clear cases.

      Delete
    36. @John Harshman: “The number of mutations in functional regions of the genome does not depend in any way on the amount of junk in the genome”

      There is no game on my side John. I just wanted to point out that your statement that the number of mutations in functional regions of the genome does not depend in any way on the amount of junk in the genome, does not apply to all mutations. That’s all.

      Regarding our discussion on a previous post ( http://sandwalk.blogspot.com/2015/03/a-physicist-tries-to-understand-junk-dna.html), it is likely that likely you didn't see the answers to you questions about Natural Selection and the concept of “biological function” as they applie to the so called “junk DNA” (jDNA).

      Here is the answer:

      “The example above is clearly about “two organisms/lineages”, but if you insist, I guess, it can also apply to “species,” although I’m not sure how you define a “species” (as you know, the definition of “species” has been a highly controversial issue) (BTW, do you have a definition of "biological function" that you think is reasonable and we can use as a reference definition?).

      Now, about the “selection”, Natural Selection that is, which you insist must be essential for anything that is deemed to be biologically functional.

      Weather strong or weak, Natural Selection is a pervasive force in evolution, and indeed Natural Selection is continuously acting on the so called “junk DNA” (jDNA). For example, when jDNA is exapted as a molecular immune protective mechanism against deleterious insertional mutagenesis in organism/lineage/species A, then this functional DNA enters positive selection.

      When this exposure ceases, and there is no need for a protective mechanism, then this DNA enters negative or purifying selection; obviously, if this selection is weak, as is the case of species with high C value, such as humans, then it cannot overcame the mutational imbalance favoring the new addition of DNA and, therefore this DNA persist.

      In light of all these facts, I think it is reasonable to replace the term “junk DNA” with the concept of symbiotic DNA (sDNA).”

      Delete
    37. Claudiu Bondea,

      "So, what are the “good arguments” for the side saying that most of the human genome if functional? Give us some."

      I have some:

      "What ENCODE researchers did not take into account is.... that evolution is slow to weed out useless features. Genetic mutations -- the drivers of evolution -- occur at random, and those that are deleterious are weeded out, sometimes over many generations. Other mutations, salubrious and inconsequential alike, get passed down to progeny. As a result, species like humans and elephants that have a small effective population size are expected to accumulate a lot of junk in their genomes."
      How do you like this statement?

      Delete
    38. Who is going to stick out his head and teach us about genetic load??? Nobody???

      Delete
    39. Claudiu,

      I'm afraid your post was sense-free. I know you think you are making an argument, but I and, I believe, everyone else here don't think you are. In general, two members of the same species do not differ in genome size by enough that there could possibly be any significant selection acting within the species. You seem to be denying that your argument is about species selection, but I don't see any alternative. You are coming across as a crank.

      Delete
    40. John Harshman: ”You seem to be denying that your argument is about species selection, but I don't see any alternative. You are coming across as a crank”

      Way to go, John! But, seriously, I was wondering when you will run out of arguments and start the game of ‘name calling'?

      Well, it was earlier than I thought. It must have been the stress caused by the two major blunders you made on this tread, the one about the multiple origin of replication in bacteria (“What they do is start the replication at multiple spots in the chromosome simultaneously”) and the other one about ’mutations’ (”The number of mutations is directly proportional to the size of the genome. The number of mutations in functional regions of the genome does not depend in any way on the amount of junk in the genome”)

      However, you were right on the money, when you wrote ”Still, I'd say that the number of retroviral insertion fixations is probably proportional to the number of neutral insertion sites, which probably does have something to do with genome size”

      So, you should feel good about yourself, again -:)

      Delete
    41. Now you're coming across as a crank and a tone troll. Are you or are you not proposing species selection?

      Delete
    42. So, you still don't feel good about yourself, and need to fill the void by ‘name calling’. I doubt this we’ll help, but here I go again.

      If individuals are protected against deleterious insertional mutagenesis by ‘symbiotic DNA’ (incorrectly called “junk DNA”) then, obviously, the population, species, or lineage are also protected.

      Delete
    43. Claudiu,

      Do you in fact know what natural selection is and how it works, and what species selection is and how it differs from natural selection?

      Delete
    44. John Harshman says: ”Do you in fact know what natural selection is and how it works, and what “species selection” and is and how it differs from natural selection?

      John,

      There is only one kind of selection in nature. It is called natural selection. However, natural selection can be considered to act at different levels of biological organization, such as at the level of a gene, an organism or, indeed, a species, which are called units of selection.

      Obviously, you cannot ask how “species selection” differs from “natural selection” because species selection *is* natural selection at the level of species.

      Delete
    45. L.M. I don't know why that happened. Why did lecturers abandon prokaryotes?

      I recently lamented the converse on the ap biology teachers' forum

      Larry, I need to thank you for getting me reread Stephen Jay Gould. I recently cited him with: There is no substitute for detailed knowledge of natural history and taxonomy... S.J. Gould

      The new direction that is decidedly molecular and anti-"classical" ignores taxonomy such that teachers spend too much time on Prokaryotes and far too little time on the remaining Tree of Life.

      As a result of too little knowledge, students suffer from the impression that that evolution represents some vector of progress and that humans represent some apex of evolution.

      Delete
  3. @ Laurence A. Moran:

    In the New York Times Magazine article you are quoted as follows:

    ”Those competing approaches made it clear that the effort to understand the genome was still very much a work in progress. “The most knowledgeable scientists recognize that the issue is not settled,” Moran wrote.”

    If the quote is correct and you believe that “The most knowledgeable scientists recognize that the issue is not settled” (emphasis added), then why have you *settled the issue* here at Sandwalk by concluding that the so called “junk DNA” is non-functional?

    Or, I misunderstood your position?

    ReplyDelete
    Replies
    1. Or, I misunderstood your position?

      Of course you've misunderstood. You always do.

      For the benefit of others. The controversy over junk DNA is still a legitimate scientific controversy. There are some good arguments on both sides. As with most controversies, each side has strong opinions about which interpretation is correct. I feel very strongly that I am right and the opponents of junk DNA are wrong and that's the point of view I argue on Sandwalk. It's settled as far as I'm concerned.

      Carl Zimmer's piece was an attempt to show the general public that the death of junk DNA has been exaggerated. My quote supported that part of his article. The idea that most of our genome is functional is NOT settled.

      For the benefit of Claudiu Bandea, I've warned you already about your behavior. It looks to me like you are deliberately trying to misunderstand everything I say. Please stop.

      Delete
    2. Laurence A. Moran says: “The controversy over junk DNA is still a legitimate scientific controversy. There are some good arguments on both sides”

      Can anybody clarify: (i) what is the scientific controversy that Larry states is still legitimate, and (ii) what are the two sides that he states are supported by good arguments?

      The reason I ask is that, to my knowledge, the legitimate scientific controversy is whether *most* of the so called “junk DNA” is functional, or whether *most* of this DNA is not functional. But, I’m not sure what are the “*good arguments* on both sides"?

      Delete
  4. Larry had called attention to them in the post, so I went and read the comments on the online version of Carl Zimmer's article. Very depressing. For decades we have put up with nature documentaries on television where the narrator firmly assures us that everything is optimal in nature, and nothing is wasted, it's all for a Greater Purpose. Biologists knew better, but this seemed harmless enough, so we did not object.

    Now we are dealing with the consequences: laypeople commenting who are just sure that all that extra DNA must be there for a Greater Purpose. Worse yet: more than half of genomicists and molecular biologists agree with this. I guess they saw the same nature documentaries. Of course they also like to think of the cell as one big optimized machine. And if all that is not junk DNA, just think of how many millions of dollars worth of grants will be needed to understand it.

    I had been telling people that the Encode fiasco would set the public understanding of junk DNA back ten years. Now I am not so sure. Maybe it's more like 20 years.

    ReplyDelete
    Replies
    1. On the contrary, I think that the ENCODE fiasco has brought to light many of hyperadaptationalist crap that has been going around. Without the ENCODE fiasco we wouldn't have had Dan Graur's Immorality of TV sets paper. Without ENCODE Ryan and I would not have written our PLoS Genetics article. Even if we did write it, likely PLoS Genetics would not have been interested in publishing it. And without all of these events, we would not have had Carl Zimmer write up his piece in the New York Times.

      One step back, 1.1 steps forward.

      Delete
    2. Those papers were only read by scientists

      ENCODE was all over the media, not just the NYT. The Zimmer article is too little too late to make the same impact

      Delete
    3. It's more like 1 step back, various scientific papers achieving 0.1 steps forward, and Carl Zimmer another 0.1 steps forward worth of popularization. Compared to the torrent of mindless responses tp the ENCODE announcements in the popular science (here is Ryan Gregory's depressing collection of links), Carl Zimmer's article is at least a step in the right direction. Let's be grateful to Carl for not joining the stampede.

      But in terms of public perception and the views of a great many genomicists and molecular biologists, we are still not caught up with where we were the morning before the ENCODE press conference.

      Delete
    4. Joe says: "laypeople commenting who are just sure that all that extra DNA must be there for a Greater Purpose. Worse yet: more than half of genomicists and molecular biologists agree with this."

      I really don't think it's more than half. I think it's a very vocal minority that has the ear of the muggle press because the muggle reporters need to market revolutions and paradigm shifts to sell papers. "Turning rebellion into money" as the Clash would say.

      I know molecular biologists; if they give junk DNA more than two minutes' thought, they realize most of our genome has to be junk. They love structure-function relationships; if it has no structure or no function, they got no dog in that fight.

      Delete
    5. I agree with Joe.

      Wouldn't it be nice if Nature and Science were to each publish a mea cupla explaining their complicity in the ENCODE publicity fiasco? Both journals have been making noises about the quality of science journalism. Is it too much to ask that they examine their own role?

      Delete
    6. Joe Felsenstein says: ”But in terms of public perception and the views of a great many genomicists and molecular biologists, we are still not caught up with where we were the morning before the ENCODE press conference”.

      Joe, I think you underestimate the intelligence and knowledge of the “great many genomicists and molecular biologists”, seriously.

      The scientists working in the field of genome biology and evolution knows very well that 90% or more of the human genome does not perform information-based biological functions. That’s elementary knowledge that has been established for decades.

      However, many of these scientists prefer to keep this knowledge quiet for obvious reasons, just like you stated in your comment above “And if all that is not junk DNA, just think of how many millions of dollars worth of grants will be needed to understand it.

      However, we should not blame the scientists, but on our corrupt ‘science system’, particularly as it orbits around funding, which is plagued by dishonesty, some more obvious than other. For example, without hype and distorted reports, few grant applications or research programs would become competitive and get funded.

      In this corrupt system, many scientists have little choice but to adapt to the dictum “be dishonest or perish.”

      Delete
    7. @Diogenes, I wish I had your optimism. But paper after paper, and discussion after discussion with those around me have put me in the same frame of mind as Joe's original comment. There is a real "if I can see it, it must be important" mentality out there at the moment.

      One "gem" from the last ToC I skimmed;
      http://nar.oxfordjournals.org/content/early/2015/02/03/nar.gkv048.abstract

      "The human genome contains about 1.5 million Alu elements, which are transcribed into Alu RNAs by RNA polymerase III. Their expression is upregulated following stress and viral infection, and they associate with the SRP9/14 protein dimer in the cytoplasm forming Alu RNPs. Using cell-free translation, we have previously shown that Alu RNPs inhibit polysome formation. Here, we describe the mechanism of Alu RNP-mediated inhibition of translation initiation and demonstrate its effect on translation of cellular and viral RNAs. Both cap-dependent and IRES-mediated initiation is inhibited. Inhibition involves direct binding of SRP9/14 to 40S ribosomal subunits and requires Alu RNA as an assembly factor but its continuous association with 40S subunits is not required for inhibition. Binding of SRP9/14 to 40S prevents 48S complex formation by interfering with the recruitment of mRNA to 40S subunits. In cells, overexpression of Alu RNA decreases translation of reporter mRNAs and this effect is alleviated with a mutation that reduces its affinity for SRP9/14. Alu RNPs also inhibit the translation of cellular mRNAs resuming translation after stress and of viral mRNAs suggesting a role of Alu RNPs in adapting the translational output in response to stress and viral infection. "

      Delete
  5. I also get the impression that Claudiu Bandea is often misconstrued.

    Here is one one salient quote that I found most intriguing:

    Larry Moran to Claudiu Bandea You seem to be terribly confused about this. I can understand why Tom is confused but you should know better. Ford Doolittle cannot be a junk DNA supporter if he believes that most of the genome has a bulk DNA function. He's merely acknowledging that you can't rely exclusively on lack of sequence conservation as proof that the DNA has no function.

    OK, I admit it – I am but a humble high school teacher and I readily concede that perhaps far too often I am easily confused. That would explain why I took it upon myself to contact Ford Doolittle directly. I was honored by Professor Doolittle's patient and indulgent answers to my queries. Yes, perhaps English is my second language … ditto Claudiu…

    The bottom line still remains: Godamit! Just read for yourselves what Ford Doolittle said in Ford Doolittle’s own words!!!!

    … and the inescapable conclusion becomes unavoidable! On this particular score: Claudiu Bandea is correct and Larry Moran is wrong…

    Let’s be clear here. Given my limited credentials, I can only comment that Claudiu Bandea is correct and Larry Moran is wrong on the sole and solitary question: “What did Ford Doolittle actually say” as opposed to “What did Larry Moran think Ford Doolittle should have said”.

    Clearly, even to the non-conoscenti, there clearly are subtleties and nuances that are being overlooked by some present.

    ReplyDelete
  6. Unless I am really missing something, some versions of the rebuttal suggesting the "Onion Wins" misses the mark altogether.

    The perplexing question requiring address does not revolve around how much more DNA an onion has vs. a human. I have no problem with the notion that onions are metabolically more sophisticated than humans.

    What I at first found head-scratching is the notion that some species of onions have multiples of DNA compared to other similar plants and even other onions. It is this variable multiple conundrum that lends credence to the gainsayers proclaiming the c-value paradox.

    First things first: the argument against teleology is misapplied imho... Yes, evolution does not function with an eye to the future, meaning there can be no selection for future utility. The point remains that those organisms that indeed do have redundant DNA will eventually enjoy a selective advantage in THE LONG RUN! Redundant DNA may occur in a variety of multiples and still remain useful in the long run but when those multiples run up too high, they become a metabolic burden in the short term, so there must exist some sort of balance with multiples of middle repetitive DNA occurring in some +/- multiples.

    So to reiterate: The contention stands that those organisms that indeed do have redundant NON-INFORMATIONAL DNA will have a selective advantage in THE LONG RUN! Meanwhile, Graur's Genetic Load rebuttal only applies if we are discussing essential DNA, not DNA that is passively useful but not essential and effectively redundant.

    Please do not read more into what I have written than intended. I merely am restating Claudiu Bandea's/Ford Dolittle's clarifications as I understand them.

    There: I have set up the strawman. I would be grateful if any were to knock it down.

    ReplyDelete
    Replies
    1. What exactly does "IN THE LONG RUN" mean in biological terms? It would seem to be either a very small but constant selection coefficient or a large but very rarely occurring selection coefficient. But either of those, if too small or too rare, will not be a significant evolutionary factor now. For example, if being small is strongly selected for when an asteroid hits the earth, that will change the nature of the biota immediately after the impact but will have no effect before the impact, and the immediate effect will disappear in a few million years.

      Delete
    2. Hi John

      May I start with a preemptive thank your for your constant patience and indulgence. I and my students remain in your debt!

      Let's ensure we are on the same page here.

      I think it fair to say there exists hierarchy of selection (again thanks to Larry Moran for reigniting my enthusiasm for Gould's essays which prompts this reply):

      DNA/genes
      cells
      individual
      species
      larger clades

      Delete
    3. Tom,

      I hesitate to refer to that as a hierarchy. Selection at the DNA and individual levels is more or less the same thing viewed in different ways. Selection at the cellular level is mostly irrelevant to evolution, unless those cells are gametes. Selection at the species level probably exists but is a weak force. I don't see there being any selection at the "larger clades" level. I presume that you will eventually try to make a connection to the subject we were discussing.

      Delete
    4. Hi John,

      Nothing profound, just that I was thinking of selection at the species level(admittedly weak) but significant nonetheless when I refereed to "in the long term".

      I remain unclear why you would object

      Delete
    5. I don't actually see why species selection should be a long term phenomenon much more than individual selection is. It seems to me that it acts over more or less the same time period, and it responds to rare events in the same way too: the rare event happens, selection occurs rapidly and briefly, and things then start heading back toward where they were.

      One might argue that contingency has a greater impact given short, sharp shocks than in long-term, gradual selection. But again that would seem to apply to both species and individual selection.

      Delete
    6. Hi John,

      My understanding of selection at the species level is exactly the converse of yours. Selection at the species level is much harder to observe than selection at the cellular, or even the individual, level because species selection takes place over millions of years. (ergo my citation of "long term")

      for example:
      http://www.annualreviews.org/doi/abs/10.1146/annurev.ecolsys.39.110707.173510

      Delete
    7. Hi John - to follow up

      In any case, I would like to rephrase (in terms a student can understand) what I believe to be Claudiu Bandea’s (not to mention Ford Doolittle’s) clarification of the role of “Bulk DNA” in evolutionary terms (in the grander scheme of things).

      I humbly suggest that perhaps Bulk DNA’s selection advantage may not be immediately obvious at the level of individual organisms but nonetheless can remain significant in evolutionary terms at the species level.

      If selection at the species level indeed favors species with some optimal (I think of Goldilocks just right) excess of bulk DNA +/- certain confounding levels of tolerance, then those species (so endowed) will eventually become more common than those species lacking similar levels of bulk DNA.

      And lo and behold, “Frugal DNA” seems to be a minority representation whereas species with enhanced Bulk DNA is seems to dominate.

      OK - I think I see where I am setting up the strawman for you to knock down, but bear with me...

      I think I am reiterating David Jablonksi’s logic; but I am focusing on “genome distribution”, as it were, where Jablonski focuses on paleontological data of “geographic ranges”.

      More than once, I floated trial balloons speculating whether parasitic DNA can be co-opted into becoming symbiotic DNA in different lineages even when discussing different sequences.

      I was thinking, of course, of human Alu and murine B1

      In other words DNA can have a non-informational function without sequence conservation across lineages. Now this may not be exactly how the authors of ENCODE originally phrased their thesis and perhaps those ENCODE authors are guilty of switching definitions in mid-stream (so to speak).

      That said, I would venture to suggest that you and Larry may (emphasis on the word “may”) be guilty of inadvertent (emphasis on “inadvertent”) disingenuity no less egregious, by moving the goal posts (as it were) when Claudiu Bandera floats his trial balloons.

      For example, it would appear to me that you and Larry are retreating from an earlier contention that

      If having junk DNA were a clear advantage for future evolution then the genomes of all extant lineages should have lots of junk DNA and should make lots of lncRNAs.

      http://sandwalk.blogspot.ca/2014/09/are-lncrnas-really-mrnas-in-waiting.html

      Please… correct me if I am wrong. I really want to make sure I am getting this right.

      Delete
    8. I'm afraid your clarifications serve only to further confuse your point. First, genome size is not a species-level trait and so can't be subject to species selection according to Jablonski's (really Vrba's) definition. However, I don't like that definition and would accept the possibility anyway. It should be possible to test the claim that increased genome size is associated with increased diversification rate, and my impression is that the test would produce a negative result. Claudia, on the other hand, thinks it's purely a local effect, reacting to particular environments, which would be difficult to test, since in this case the environment and the response to it are the same thing.

      Does species selection take a long time? Well, sort of. If we're talking about the full, long-term trend in a large clade, then yes. But if we're talking about individual selective events, i.e. the extinction or speciation of one species, then no. One must ask what the mechanism would be here; I gather that you propose not increased speciation but reduced extinction. Is that right?

      Anyway, are we agreed that junk DNA can't plausibly have any effect on selection within populations? If so, we are left with species selection (my definition, not Jablonski's). Note that species selection is a weak force. If there's any within-population selection in the opposite direction, species selection will lose out. Only if within-population variation is neutral (or non-existent) can species selection have an effect. Thus it's problematic to talk about any adaptive role, whether bulk or sequence-specific.

      Even if junk DNA has a bulk role, this of course has absolutely nothing to do with anything ENCODE ever talked about or looked at, so it's absurd even to bring up ENCODE in this context.

      Delete
    9. Hi John. Thank you for your detailed response.

      JH: First, genome size is not a species-level trait and so can't be subject to species selection according to Jablonski's (really Vrba's) definition. However, I don't like that definition and would accept the possibility anyway.

      TM: There are many different definitions of speciation, but a recurrent theme is reproductive isolation. Variation in genome size to my reading constitutes the epitome of reproductive isolation according to my understanding of the Dobzhansky-Muller model. In other words, yes, genome-size is a species-level trait!

      http://www.nature.com/scitable/topicpage/hybrid-incompatibility-and-speciation-820

      This seems so obvious to me that I fear we must be talking at cross-purposes and I am clearly missing something.

      Delete
    10. JH: It should be possible to test the claim that increased genome size is associated with increased diversification rate, and my impression is that the test would produce a negative result. Claudia, on the other hand, thinks it's purely a local effect, reacting to particular environments, which would be difficult to test, since in this case the environment and the response to it are the same thing.

      I do not want to put words into Claudiu’s mouth, but I read him exactly the opposite. Claudiu seems to be suggesting that genome expansion serendipitously permits jDNA to offer some protective role of against mutations. If I am interpreting Claudiu correctly, he would predict that that the immediate effects of increased genome size would be associated with a decreased diversification rate (not an increased rate)

      Delete
    11. JH: One must ask what the mechanism would be here; I gather that you propose not increased speciation but reduced extinction. Is that right?

      Again,I do not want to put words into Claudiu’s mouth, but if I am getting this all correct then Claudiu seems to be stressing the importance of reduced extinction as opposed to increased speciation… uhm but only in the short term population level.

      If Claudiu is correct, then bulk DNA offers some form of protection to the host by offering some larger decoy target for suppressed and ultimately rare deleterious events thereby providing "cover" for essential functional regions. That means Claudiu is proposing a plausible non-informational function for so-called junk DNA (he acknowledges others) that confer a positive effect (albeit superfluous, non-essential and redundant) within populations?

      The fact still remains that this bulk DNA offers the long-term evolutionary wherewithal for the host to evolve defense mechanisms against virus mediated indels including the eventual co-opting of previously parasitic DNA into symbiotic DNA (my preferred hobby-horse)

      The problem is that we need not compartmentalize selection at the species level vs the individual level. Of course there must be a trade-off for selection at the gene vs. the individual level just as there is a trade-off for selection at the individual level vs. selection at the species level. Much overlap is occurring which I do not think represents “confusion” (as you suggested earlier) but rather complexity.

      Delete
    12. Finally John, to answer your question, at the species-level is increased genome size associated with increased diversification rate? That would depend whether we are isolating reduced extinction as a consideration vs. increased speciation. I am definitely in over my head and really am not qualified to offer an opinion. My guess? I think both must be operative here. Greater genome fluidity must confer an increased rate of diversification in “the long run” balancing Claudiu’s apparent proposed mechanism of reduced extinction.

      ITMT, I wonder out loud whether the answer to that question also varies according to lineage somehow ex Ecydysozoa vs Locotrophozoa vs Deuterostome vs. any other lineage including Onions'. Something must be happening in a lineage specific manner. I am thinking of the surprising stability of the elephant shark genome for example.

      I agree with your take on ENCODE. As I already mentioned above, they were most disingenuous.

      I thank you yet again for your patience and your indulgence. I eagerly await any correction you may offer.

      as always, best regards

      Delete
    13. TM: There are many different definitions of speciation, but a recurrent theme is reproductive isolation.

      The confusion is not over speciation but over the definition of species selection. Jablonski makes his definition (which is, again, Vrba's) even in the abstract. To fit his definition, selection must be based on a species-level property, i.e. one that isn't a characteristic of an individual. Genome size does not fit that requirement, making your appeal to Jablonski problematic.

      If I am interpreting Claudiu correctly, he would predict that that the immediate effects of increased genome size would be associated with a decreased diversification rate (not an increased rate)

      If you're reading him correctly, then selection at the species level would lead to decreased genome sizes. I suspect you are not reading him correctly. I'm afraid that I think your understanding of what Claudiu is saying is even more confused than Claudiu's own understanding. I can't make sense of either of you. I think you're using "complexity" to hide a lack of mechanism.

      "Diversification rate" is a technical term to describe the increase (or possibly decrease) in species numbers over time within a group. It's equal to speciation rate minus extinction rate. Increased rate of diversification doesn't balance reduced extinction; reduced extinction is one possible component of increased diversification.

      If the answer is lineage-specific, then it's not an answer. There's a separate answer for each lineage.

      I'm sorry, but I still think you're hopelessly confused about all this. We're back to the idea that an increased rate of insertion is a defense against an increased rate of insertion.

      Delete
    14. @ Tom Mueller and John Harshman

      I want to ask both of you, as well as other readers here at Sandwalk, to clarify your position on the following issues:

      (1) Let’s assume that most of the genome in organisms with high C-value, such as humans, contains sequences that have accumulated simply because of a mutational imbalance favoring amplification of “non-specific DNA” versus deletion. Is this scenario possible? My answer is *yes*. What is your answer?

      (2) Let’s assume that these organisms experience an invasion of endogenous and exogenous genome inserting elements. Can this “non-specific DNA” provide a protective mechanism against deleterious insertional mutagenesis? My answer is *yes*. What is your answer?

      Delete
    15. 1. Yes, duh.

      2. You're asking if something can provide protection against itself? How would we tell? Whether it did or it didn't, we would expect species with lots of insertions to have lots of insertions. My answer is "Mu".

      Delete
    16. I don't know much about junk DNA but from what I have read the may be only one conclusion (or one of the conclusions) that the more complex an organism (depending on the definition of complexity unfortunately) the more jDNA the organism ha,s. The question remains, why? And how does one define complexity? That's just my take. Well, I thought I would give it a try. Something to consider. Maybe? Maybe not.

      Delete
    17. Pest,

      You should have stopped after "I don't know much about junk DNA". Up till that point you were correct. Everything after that is wrong. Well, up to "Maybe not."

      Delete
    18. Let's see the proof you are so confident about. I'm pretty sure you will be paddling back in one way or another very soon.

      Delete
    19. Read anything Larry has posted on this subject. Your claims are directly refuted by the mere existence of the C-value paradox. Are you familiar with the term?

      Delete
    20. only one conclusion (or one of the conclusions) that the more complex an organism (depending on the definition of complexity unfortunately) the more jDNA the organism ha,s.

      Consider the onions of the field, Pest. They toil not, neither do they spin, but they've got a s**tload of DNA.

      Delete
    21. Hi again John and again thank you for again taking the time to help me out here. I remain forever grateful and in your debt.

      JH The confusion is not over speciation but over the definition of species selection. Jablonski makes his definition (which is, again, Vrba's) even in the abstract. To fit his definition, selection must be based on a species-level property, i.e. one that isn't a characteristic of an individual. Genome size does not fit that requirement, making your appeal to Jablonski problematic.

      My intuitions suggest otherwise. Earlier, I cited Gould’s essay in Horses Toes and Hens Teeth as my impetus to lend support to Claudiu’s hypothesis. My understanding was that genome size could be under selection pressure simultaneously at multiple levels. If I am reading this link (written by T. R. Gregory) correctly ( http://tinyurl.com/neymjw7 ) genome-size can concievably fall under the category of “emergent fitness” at the species level exactly along the lines that Vrba was talking about. Controversial? Yes! Contentious, maybe? Possibly …but cogent nonetheless.

      Please correct me if I am wrong. I am not asking you whether or not you agree or disagree, but merely whether or not such lines of thought are at a minimum plausible.

      Delete
    22. re: TM: If I am interpreting Claudiu correctly, he would predict that that the immediate effects of increased genome size would be associated with a decreased diversification rate (not an increased rate)

      JH If you're reading him correctly, then selection at the species level would lead to decreased genome sizes. I suspect you are not reading him correctly.

      I took the liberty of contacting Claudiu by email (as I did earlier with Professor Doolittle, as mentioned above). Claudiu confirms that I have understood him exactly correctly. ITMT, I am unclear why you made the jump to suggest that Claudiu’s logic would necessitate that “selection at the species level would lead to decreased genome sizes”. You lost me there.

      JH: I'm afraid that I think your understanding of what Claudiu is saying is even more confused than Claudiu's own understanding. I can't make sense of either of you. I think you're using "complexity" to hide a lack of mechanism.

      Hmmm… Forgive me but my quick reading of the ‘‘Lloyd-Vrba debate’’ suggests the question is indeed complex, especially given different levels of selection may be happening simultaneously. Again I thank you for directing my continued education from afar. Your replies have obliged me to foray into literature searches that would never have occurred to me by my lonesome. I still need to read through this great article by Gregory. I offer it as worthy of perusal for others’ consideration http://www.genomesize.com/rgregory/reprints/Macroevol.pdf

      Delete
    23. JH: If the answer is lineage-specific, then it's not an answer. There's a separate answer for each lineage.

      Uhmmm… yes may prove to be correct, bringing me back yet again to my invocation of “complexity”. I was thinking of avian genome sizes which prompted me to some more google-whacking. Again I stumbled across Gregory:

      Specifically, metabolic constraints do not appear to be relevant in amphibians, whereas developmental influences seem substantial. This situation is the opposite of that found in homeotherms (Chapter 3). Developmental complexity, in particular, seems to be an important correlate of genome size in amphibians, and may help to explain the broad but non-random distribution of C-values in this class. http://tinyurl.com/pnjo6j2

      So, I repeat. Lineage increases the complexity (not the confusion) of answering this whole question.

      JH I'm sorry, but I still think you're hopelessly confused about all this. We're back to the idea that an increased rate of insertion is a defense against an increased rate of insertion.

      I admit – my understanding is very naïve and more than likely confused if past history provides precedence. Again I thank you for your efforts to bring me up to speed. That said, (even from my naïve perspective) I think your reductio ad absurdum about an an increased rate of insertion is a defense against an increased rate of insertion. is most unfair. There is far more to the repertoire of so-called Middle Repetitive DNA sequences than just merely mobile genetic elements, all the while leaving still open the question of the functional role(s) of Highly Repetitive DNA sequences!

      Delete
    24. @ judmarc

      I remember my Freshman Bio lab instructor (so many years ago) explaining how plants have a more difficult job than animals. Motile animals (within limits) can pick up and avoid stress or challenge. Sessile plants often need to come up with a biochemical solution (as it were) or perish. I always thought that Onions (any plant actually) to likely be metabolically more complex than an animal.

      I am just airing prejudice here and welcome correction.

      Delete
    25. Post script to John Harshman....

      As I mentioned earlier - I ask you not to read more into what I am saying than intended. I agree with you and others that many (not all) in the ENCODE camp were disingenuous and I am distancing myself from them altogether.

      Delete
    26. Tom,

      I can't do more than I already have. Genome size is a characteristic of an individual, not a species-level character. I don't understand how you can suppose it to be anything else. I think both you and Claudiu are hopelessly confused about levels of selection and about what could be subject to selection. I can't explain any better than I already have. And "complexity" isn't an explanation.

      Delete
    27. John

      Deep sigh… This evokes sad memories past when you almost had to give up on me before I finally "got it". I am thinking about "rooting" phylogenetic trees, if you remember. Again I thank you for your patience! My students thank you!

      I just spammed you with many links. My apologies. Let’s just focus on ONE link.

      Please read page ONLY page 65 & page 66 of the this link (Just two pages, is all I ask)

      http://tinyurl.com/neymjw7

      Bottom Line:

      Genome size can vary according to the biology of the organisms in question (so lineage remains an important consideration)

      According to some (Gould for example) genome size itself MAY be under simultaneous selection at multiple (expanded hierarchical) levels, including the species level.

      I merely report what I read!
      Please tell me – wherein lies my confusion?

      Delete
    28. I think you mistake what Gregory is saying. He isn't referring to species selection. He's referring to multi-level selection in which intra-genomic selection (i.e. the proliferation within the genome of elements that are better at proliferating) vs. selection on genome size at the individual level. And in the latter case he's referring to gross physiological effects. He uses species selection as an example of multi-level selection and as analogy to individual selection in an intragenomic/individual selection regime, but I don't see anywhere that he actually talks about species selection acting on genomes.

      This seems to have nothing to do with your attempted precise or with what you were talking about, so far as I can tell. Nor does it appear to have anything to do with Claudiu's hypothesis.

      Delete
    29. John Harshman: “1. Yes, duh.”

      I must confess I had some difficulty in coming up with a question that I thought John might give a straight answer, but apparently it did pay off :).

      Nevertheless, the question is relevant as it brings forward a critical issue regarding the evolution of genome size and the putative functionality of most non-informational genomic DNA (niDNA), that is the fact that some niDNA can accumulate in the absence of an *immediate* benefit (this bring into perspective Tom Mueller’s emphasis on “long term”).

      Addition or deletion of genomic DNA represent mutational events. Like any mutational event, insertional mutants enter the realm of Natural Selection (NS), whether strong, moderate, or weak. Nevertheless, similar to all biological processes, NS has a stochastic dimension, usually referred to as genetic drift, and the weaker NS is, the larger its stochastic dimension.

      It is obvious, however, that regardless of its natural history, niDNA can be exapted into performing essential biological functions, just as I hypothesized (http://biorxiv.org/content/early/2013/11/18/000588).

      John Harshman: ”2. You're asking if something can provide protection against itself? How would we tell? Whether it did or it didn't, we would expect species with lots of insertions to have lots of insertions. My answer is "Mu".”

      Now, this is an answer more in line with my expectations from John (when he doesn’t fall victim to the ‘name calling game’ :). Tom has already address some of Johns’s points “I think your reductio ad absurdum about an an increased rate of insertion is a defense against an increased rate of insertion. is most unfair. So, I will only address John’s last sentence: “My answer is "Mu". Unless I give John too much credit regarding his familiarity with the insertional mutagenesis phenomenon, this is a profound insight into the extraordinary selective pressure associated with deleterious insertional mutagenesis.

      As many readers know, Mu is a temperate bacteriophage that uses DNA-based transposition in its lysogenic life cycle. Mu is one of the most studied transposable elements as it has very high transposition efficiency and relatively low target specificity. Remarkably, Natural Selection has driven the evolution of a Mu genome immunity mechanism that protects the virus against auto-integration into its own proviral-genome (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837660/pdf/1759-8753-1-8.pdf). Interestingly, this protective mechanism is on top of another protective mechanism, called “cis-immunity mechanism,” which protects the host genomic regions flanking the proviral genome from insertional mutagenesis. Just fascinating!

      Delete
    30. John Harshman,

      "You're asking if something can provide protection against itself?"

      If this is not the answer the other option could be that the protection was designer.

      Delete
    31. Claudiu Bandera,

      "Remarkably, Natural Selection has driven the evolution of a Mu genome immunity mechanism that protects the virus against auto-integration into its own proviral-genome."

      This is very interesting. But don't different species have different immunity systems? Could the variation in jDNA size be partially explained by the variation in immune system differences between species?

      Delete
    32. Pest says: This is very interesting. But don't different species have different immunity systems?

      Good that you brought this up, Pest. We all know, although rarely reflect upon, that some of most striking advances in molecular biology and genetics have been facilitated by the discovery and the use of “nucleic acid-based molecular immune systems” that evolved as protective mechanisms against viruses.

      Indeed, the restriction/modification protective system has led to the ‘genetic engineering’ revolution, the micro RNAs, which have evolved as a protective molecular immune system against viruses and eventually been coopted by the host for gene regulation, has been instrumental in endless molecular genetics studies, and, we are in the mist of one of the biggest revolution in in vivo genome manipulation using the CRISPR/Cas adaptive immunity molecular system that has evolved as protective mechanism against viruses.

      Pest, interesting that you reiterated one of Johns’ remarks "You're asking if something can provide protection against itself?" (see above), because as I recently pointed out (http://biorxiv.org/content/early/2013/11/18/000588)that’s exactly what happens in the CRISPR/Cas adaptive immunity molecular system:

      “Indeed, similar to the CRISPR system, in which viral sequences have been co-opted as an adaptive antiviral defense system [7], the defense mechanism provided by jDNA is a classic case of ‘fighting fire with fire’.”

      Apparently, though, John is not familiar with this system.

      Delete
    33. Claudiu Bandea

      This is all very, very interesting and very complex to me. I would like to do some reading on the theme. Can you suggest some websites or books? I'm going on vacations so I will have a lot of spare time.

      Thanks,

      Delete
    34. Hi again John

      I hesitated to jump in again given the ever increasing acrimony in the pursuit of debating points demonstrated by various sides in this debate. Myself – this is an important topic that I desire to broach in class as well as share with my colleagues on the ap bio forum (of course, full credit will be accorded to you as I direct my fellow teachers to this forum). Other than that, I desire no part in this “debate”. So again, I thank you for your patience and your indulgence.

      Re: JH I think you mistake what Gregory is saying. He isn't referring to species selection. He's referring to multi-level selection in which intra-genomic selection (i.e. the proliferation within the genome of elements that are better at proliferating) vs. selection on genome size at the individual level. And in the latter case he's referring to gross physiological effects. He uses species selection as an example of multi-level selection and as analogy to individual selection in an intragenomic/individual selection regime, but I don't see anywhere that he actually talks about species selection acting on genomes.

      OK, I hear you but I read Gregory otherwise. I suspect my interpretation is indeed correct. (maybe one of us should email Gregory as well)

      First of all I direct your attention to Gregory’s citation of Gould. Basically, I see Gregory grabbing Gould’s football and running with:

      Might there not be a hierarchy of individuals, with legitimate categories both above and below bodies: genes below, species above? (I confess to what evolutionists call a "preadaptation" for favorable response to the selfish DNA hypothesis. I have long argued that species must be viewed as true evolutionary units and that macroevolutionary trends are often powered by a "species selection" that is analogous to, but not identical with, natural selection acting upon bodies.) Selfish DNA may do nothing for bodies, but bodies are the wrong level of analysis.

      …In hierarchical models, levels are not independent, walled off by impenetrable boundaries from those above and below. Levels leak and interact.

      http://tinyurl.com/p88guj4

      I really need to thank you for raising my understanding to a higher level. Until your answers prompted some further research on my part, I never realized that, Gould and Vrba invented the term “exaptation”. This is a great article!

      http://www2.hawaii.edu/~khayes/Journal_Club/fall2006/Gould_&_Vrb_1982_Paleobio.pdf

      Delete
    35. Hi again John

      Re: JH This seems to have nothing to do with your attempted precise or with what you were talking about, so far as I can tell. Nor does it appear to have anything to do with Claudiu's hypothesis.

      Actually, I did ask Claudiu about that (by email) and he did confirm that indeed he was thinking about the non-adaptive expansion of ALL repetitive DNA (not just transposable DNA) presenting an “exaptation” at the both the individual population and species level. Of course, none of what Claudiu proposes lends support in any way to the hype and hyperbole from certain (not all) ENCODE corners.

      But to be clear here, let’s say you are correct and the conceptual jump to species selection is incorrect. Claudiu still did propose two “exaptations”; one “short-term” and the other “long-term” that offer selective advantage (minimal to be sure, but “functional” nonetheless) to certain categories of jDNA.

      I counter with “why not?”…

      Delete
    36. Tom, You are certainly free to think that your interpretion is correct. I don't see how you can possibly have that interpretation if you read those two pages, but you can do that.

      In your quote, Gregory is talking about an appreciation for species selection, but it's unattached to anything regarding genome size. When he talks about genome size, he's only talking about within-genome vs. individual selection. I too think that species selection is responsible for some things (though Vrba would call it only species sorting in all the sorts of cases I'm thinking of; no emergent features). But I don't see it working here.

      Delete
    37. Why not? Because, first of all, Claudiu's hypothesis is unclear; most especially, the mechanism by which it's an adaptation and by which it spreads through a population or clade is unclear. And second, the existence of any selection is implausible for reasons that have been advanced many times.

      Delete
    38. Hi John

      And yet again I thank you for your patience and your indulgence. I really do want to pursue this topic in class, and I do not want to be the cause of confusion.

      JH: You are certainly free to think that your interpretion is correct. I don't see how you can possibly have that interpretation if you read those two pages, but you can do that.

      In your quote, Gregory is talking about an appreciation for species selection, but it's unattached to anything regarding genome size.


      John – I am certain my interpretation is correct. It has to be. Check out the second page.

      Again, these concepts—selection versus sorting, emergent vs. aggregate characters, the effect hypothesis versus emergent fitness, and context-dependent sorting- were all developed with the species level in mind. The question here is whether they apply as well (or perhaps even better) to questions of genome evolution . That they do is apparent when the preceding discussion of genome size evolution is recast in the following terms: …

      OK – “genome evolution”… is Gregory indeed referring to any relationship to “genome size” and c-value considerations? Again, I say yes, but only because I read further in Macroevolution, hierarchy theory, and the C-value enigma

      http://www.genomesize.com/rgregory/reprints/Macroevol.pdf

      But as I already mentioned above:

      …let’s say you are correct and the conceptual jump to species selection is incorrect…, my contention (confusion more likely) still stands. Claudiu is NOT proposing an adaptation. He is proposing an exaptation (again if I understand him correctly and again I hope I am not putting words into his mouth).

      JH …the mechanism by which it's an adaptation and by which it spreads through a population or clade is unclear.

      I repeat - there is no initial adaptation at individual/population level. Given the prevalent enthusiasm for Neutral Theory on this forum, I fail to understand the impasse.

      John, again I thank you for your patience which evokes memories of your past intercessions. I really do want to get this right.

      Delete
    39. I'm sorry, but you seem to be reading particular words in Gregory's article and stringing them together to tell a story quite different from what Gregory is saying. Again, he's using species vs. individual selection as an analogy to what he's talking about, which is individual vs. intragenomic selection. The mapping is species:individual and individual:"selfish DNA", where the parts before the colons are Gould and the parts after are Gregory. He is not talking about species selection involving genome size.

      If big genomes spread through a population by drift, we would expect that to happen quite rarely. Claudiu, in contrast, is proposing mutation pressure, i.e. that there's a mutational bias toward insertions vs. deletions.

      So now: how do big genomes spread through clades? What, in other words, is the mechanism of species selection at work here?

      Delete
  7. In these comparisons, "the" onion is Allium cepa, a diploid. Like humans, they have 2 copies of each kind of chromosome. The onions with lots more DNA are polyploids. They have multiple copies of each kind of chromosome, so they have multiple copies of the useful DNA as well as the junk. Polyploidy can be considered a fairly common genetic accident in plants and animals. Polyploid animals, inclulding humans, are often not viable, but plants tend to tolerate polyploidy well. Polyploidy itself can have advantages (larger cells, faster protein synthesis, overcoming barriers to self fertilization that function at the diploid level, producing fertile plants from triploids and other odd polyploids, sometimes bigger plants or plant parts), as well as problems (more DNA to copy, and maybe these other changes aren't adaptive).

    The most interesting effect of polyploidy is that the polyploid has more copies of each gene than it needs (more or less). Therefore, the organism can tolerate mutations that change the function of a gene or even make it useless. Each unnecessary gene has the potential to become something new and different.

    ReplyDelete
    Replies
    1. I had been told that there are diploid onions with quite different genome sizes. But I don't know any details.

      Delete
    2. That may also be true. I'm sorry, but I don't know.

      Delete
    3. Well, I know now. There are high polyploid wild onions, but there is also variation in the DNA content at the diploid level. I didn't know this. Interesting. I'll have to read more about it.

      Delete
    4. Of course tetraploids gradually undergo a process of diploidization that may leave lots of extra DNA for quite a while while erasing the tetraploid signature more rapidly. More but smaller chromosomes?

      Delete
  8. I think that the onions are diploidized ancient polyploids, but will have to read more. (I did an isozyme study once with Populus that were diploidized ancient polyploids. Both frustrating and interesting because the species differed in which enzymes were coded for by two homoeologous loci and which by only one.)

    ReplyDelete