Tuesday, April 01, 2014

A creationist tries to understand genetic load

Apparently there are some creationists who are slightly embarrassed that they don't understand evolution. First, there was Vincent Torley who made an attempt to understand population genetics (from the 1920s and 1930s) and Neutral Theory, which is only 45 years old. You can read his attempt at: Fixation: the neutral theory’s Achilles’ heel?. See my attempt to correct his errors at: A creationist illustrates the argument from ignorance while trying to understand population genetics and Neutral Theory.

I appear to have been partially successful because if you scroll down to the bottom of Vincent Torley's post you'll see an "update" that pretty much refutes his entire post.

The comments on Torley's post reveal that there are very few creationists who have ever heard of population genetics and Neutral Theory. Now that they've been exposed, their response is to reject it because they don't understand it. Salvador Cordova (scordova) pops up in those comments to explain that modern evolutionary theory is all wrong because of "unfixing." Apparently, evolutionary biologists have missed something important that only creationists can see. This happens a lot.

Sal is so proud of himself that he puts up another post at Uncommon Descent: Fixation rate, what about breaking rate?. One gets the impression that some of the creationists are a bit worried.

The irony is that the vast majority of creationists will have absolutely no idea what Cordova is talking about. To them, it's like he's speaking gibberish. In this case, it means that the average IDiot isn't even posting comments under Cordova's post because they don't know what to say. This is all news to them.

So, what is the great discovery that refutes population genetics and Neutral Theory? It's got something to do with the idea that for neutral alleles the rate of fixation is equal to the mutation rate. Cordova agrees with the math but thinks it is "flawed from a functional standpoint." Why? Because ...
Ok, so let’s do an experiment. Let’s subject bacteria or plants or any organism to radiation and thus increase the mutation rate mutation rate by a factor of 1 million or 1 billion. Do you think the above formula will still hold? We tried it in the lab, it killed the plants, and at some point rather than speeding evolution we are doing sterilization.
Cordova is correct. An organism will die if you subject it to massive amounts of radiation. This blast doesn't have much to do with mutation rate but later on Cordova comes closer to a serious discussion of evolutionary theory.

Here's what upsets him ...
... even with moderate rates of mutation per individual per generation, genetic deterioration will happen. Further, this claim is reinforced by the work of Nobel Prize winner Hermann Muller who said a deleterious mutation rate of even 0.5 per individual per generation would be sufficient to eventually terminate humanity. So the simple model I present is actually more generous than Muller’s. Current estimates of the number of bad mutations are well over 1.0 per human per individual. There could be hundreds, perhaps thousands of bad mutations per individual per generation according to John Sanford. Larry Moran estimates 56-160 mutations per individual per generation. Using Larry’s low figure of 56 and generously granting that only about 11% of those are bad, we end up with 6 bad mutation per individual per generation, 6 times more than the cartoon model presented, and 12 times more than Muller’s figure that ensures the eventual end of the human race.
He's talking about genetic load although he goes out of his way to avoid using that term.

Sal Cordova is correct that if the deleterious mutation rate is too high, the species will go extinct. We don't know the exact minimum number of deleterious mutations that have to happen per generation in order to cause a problem. It's probably less than two (2). It's probably not as low as 0.5. It should be no more than 1 or 2 deleterious mutations per generation.

Genetic load arguments have been around for over forty years [Non-Darwinian Evolution in 1969: The Case for Junk DNA]. Back then, they were used to explain that most of our genome is junk and mutations in that part of the genome have no effect. We now know that those arguments were correct and 90% of our genome is junk.

Imagine that there are 130 new mutations per generation. Since only 10% of our genome is functional DNA, this means that only 13 of these mutations occur in DNA that has a biological function. We know that in a typical coding region about 25% of all mutations are seriously detrimental so if all the functional region of the genome were coding region that would mean 3.25 detrimental mutations per generation.1 However, less than 2% of our genome encodes protein. The remaining functional regions are much less constrained so they can tolerate more mutations. It's likely that there are fewer than 2 detrimental mutations per generation and this is an acceptable genetic load.

All of this information is readily available in textbooks and scientific papers. It's basic evolutionary theory and facts about the human genome.

Cordova is correct to raise the point about genetic load but he is quite wrong in his calculation.

Still, we seem to be making a bit of progress because at least the creationists are talking about evolutionary theory from the 100 years after Darwin died.

Better late than never. Now all they have to do is get the facts right and they'll be ready to move into the 21st century.

Lynch, M. (2010) Rate, molecular spectrum, and consequences of human mutation. Proceedings of the National Academy of Sciences 107, 961-968. [doi: 10.1073/pnas.0912629107]

Keightley, P.D. (2012) Rates and fitness consequences of new mutations in humans. Genetics 190, 295-304. [doi: 10.1534/genetics.111.134668]

Kondrashov, A.S. (2002) Direct estimates of human per nucleotide mutation rates at 20 loci causing Mendelian diseases. Human mutation 21, 12-27. [doi: 10.1002/humu.10147]


1. Estimates of the percentage of deleterious mutations in coding regions are all over the map. I figure that most distantly related genes are only 30% identical in amino acid sequence. Some mutations in the conserved amino acid codons will be synonymous. But even if this value is 50% instead of 25%, the total number of deleterious mutations in coding regions would only be 50% × 2% × 130 = 1.3 deleterious mutations.

31 comments :

  1. Sal is of course looking for something that requires God to have monkeyed with and/or to be monkeying with our DNA. He has proposed "DNA steganography," meaning that God has put a message or messages in our DNA. (If you are old enough to remember when GM cars had a plate on the frame that you could see when you opened the driver's side door, saying "Body by Fisher," I think Sal envisions kinda the same sort of thing, but saying "Body by God." My guess is this is the reason Sal has an interest in the genome - he wants to crack that code God has cleverly inserted to keep His presence hidden.)

    Thanks for the nice reminder about genetic load and what it tells us about both junk and non-coding DNA.

    ReplyDelete
  2. Thanks Prof.

    In the comments to that article is the claim that 30–50% of single amino acid mutations are strongly deleterious (http://www.che.caltech.edu/groups/fha/publications/Romero_NRMCB2009.pdf) and that 70% of mutations within fly protein coding exons are deleterious (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1871816/)

    Is 20% a fair figure to use here?

    Also in 2009 you wrote that "there can’t be more than 0.1 deleterious mutations per individual per generation but in actual populations this value can be a bit higher" (http://sandwalk.blogspot.co.uk/2009/11/genetic-load-neutral-theory-and-junk.html)

    Why is the tolerance so much higher now (not less than 2%)?

    ReplyDelete
    Replies
    1. We don't know the exact percentage of deleterious mutations in coding regions. I changed it to 25% in the post but even if it's an unreasonable 50% that's still okay.

      Are you worried that our species is going extinct or are you questioning the estimates?

      Thanks for alerting me to the error in my earlier post where I said 0.1 deleterious mutations. I've added an update.

      Delete
    2. > Are you worried that our species is going extinct?

      I am a little curious as to whether it's possible that our recent drop in selection pressure and our new tendency to have only two children per family could lead to an accumulation of slightly deleterious mutations which could ultimately lead to our extinction.

      The reason I ask though is because it seems to be a creationist trope that we are gaining slightly deleterious mutations with each new generation. They use this as "evidence" that our genome is becoming increasingly disordered and so we must have come from an original breeding pair (hint: Adam and Eve) that had perfect genomes with no errors (no pseudogenes etc.)

      If our genetic load can be shown to be unsustainable then this is an argument for the creationist case that we were created as a distinct species.

      Delete
    3. If our genetic load can be shown to be unsustainable then this is an argument for the creationist case that we were created as a distinct species.

      If true, it would only mean that we might be doomed as a species. There's no way that all the evidence for common ancestry could be reconciled with the assumption of "the first breeding pair" with perfect genomes. Even our pseudogenes (such as GULOP or numerous broken genes in the olfactory receptor clusters) were rendered dysfunctional by inactivating mutations that happened in the common ancestor of humans and at least some other extant primates (including all apes, monkeys, as well as tarsiers in the case of GULOP).

      Delete
    4. If the argument is that we aren't extinct because not enough time has gone by since creation, then why aren't species with shorter generation times and higher mutation rates extinct yet? How can there be 500+ species of Drosophila still happily enjoying their overripe fruit?

      Oh, I know. It's because creationists don't test their arguments and think only of local, momentary triumphs.

      Delete
    5. hariseldonian,

      Another question re your first paragraph is for how long the drop in selection pressure and the two child families will last. It is still an open question at least (and a no-brainer to some) whether the prosperity that allows this happy state of affairs will be possible once we have burned off all easily extractable fossil fuels, and that is before mentioning all the other things that are on the horizon. It is likely that the accumulation of deleterious alleles should be the least of our worries.

      Delete
    6. To quote Keightley 2012 (see the link above):

      The above considerations lead to doubts about whether deleterious mutation accumulation will produce a detectable fitness loss in humans in the foreseeable future. Less speculative, perhaps, is the existence of finite global energy, food, and water resources. Coupled with expanding human populations, these factors may intensify competition and lead to stronger natural selection in years to come.

      Delete
    7. Alex: It is likely that the accumulation of deleterious alleles should be the least of our worries.

      Its ironic that the christian and conservative would be concerned about such heady scientific matters, while comprising the demographic that denies concerns about global warming, poverty, resource depletion, etc.

      Piotr quoted: Coupled with expanding human populations, these factors may intensify competition and lead to stronger natural selection in years to come.

      Is there any prediction of a second ark in the bible, or is that out of the quesiton?

      Delete
    8. Is there any prediction of a second ark in the bible, or is that out of the quesiton?

      Do you mean that at least the fresh water shortage can be fixed thanks to divine intervention?

      Delete
    9. SRM asks,

      Is there any prediction of a second ark in the bible, or is that out of the quesiton?

      The next time the gods decide to murder all of us they'll probably do it by hurling asteroids at the Earth. An ark won't save you.

      If you ask nicely, I may let you come on the secret spaceship that the gods are helping me build in my back yard. (Don't tell anyone.)

      Delete
  3. So the problem here is that a creationist doesn't understand non-coding DNA or junk DNA?

    This sounds familiar somehow...

    ReplyDelete
    Replies
    1. That seems to be an important part of the problem. Either that, or Sal Cordova is looking for ways to prove that our species is degenerating and will soon go extinct. Some will be saved in the rapture.

      Delete
    2. I was under the impression that the IDiots like slimy Sal reject the notion of junk DNA.

      Delete
    3. Either that, or Sal Cordova is looking for ways to prove that our species is degenerating and will soon go extinct. Some will be saved in the rapture.

      So IDers/creationists haven't come to grips with junk DNA in years, and here you give them an "out" in a throwaway remark.

      Perhaps it's just that, compared to good scientists, creationists aren't very creative.

      Delete
    4. That again brings up the point I raised in the previous thread: What is the ID creationist explanation for this apparent paradox? They present numbers that suggest the human species should be degenerating into a state of extinction. Instead, the population is now 7 billion and continues to increase. Aren't they disturbed by this? Shouldn't they be trying to figure out what they are overlooking? Evolutionists had to deal with the same problem, of course, and have solved it by concluding that most of the genome is junk. ID creationists don't like that solution, so they must another. Does anyone know what it is?

      Delete
    5. Correction, last line: ...so they must have another."

      Delete
    6. @lutesuite

      Their solution is that we came from a recent breeding pair that had a perfect genome with no mutations and so we are in fact going extinct as we accumulate mutations.

      Delete
    7. Hmm. Well that's what the Young Earth Creationists would say. But they are only a subgroup under the ID Creationist tent. Torley, for instance, accepts common ancestry and the correct age of the earth and the human species, AFAIK. So does this mean that all those IDiots who are not questioning Cordova's claims are, in effect, admitting that the YEC's are right? That would be quite momentous for them to finally arrive at a specific consensus regarding one of their claims, as opposed to simply making nebulous and misguided criticisms of evolutionary theory. Except that none of them even seem to realize that they have accomplished this.

      Delete
    8. @lutesuite

      Under the genetic entropy model, how would you determine if it takes 10,000 or 2 million years for humanity to go extinct? Take what physiologist Dennis Noble teaches about redundancy and fallback systems, at 16:47 in this talk:

      "Simply by knocking genes out we don't necessarily reveal function, because the network may buffer what is happening. So you may need to do tow knockouts or even three before you finally get through to the phenotype. ... If one network doesn't succeed in producing a component necessary to the functioning of the cell and the organism, then another network is used instead. So most knockouts and mutations are buffered by the network."

      And more at 19:40:

      "Is this an unusual result, ... or is it general? This study went through all 6000 genes in the organism yeast. knocking them out one by one. 80% of the knockouts were silent. So this physiological process of buffering against gene change is general. It's usual in fact. Now that doesn't mean to say that these proteins that are made as a consequence of gene templates for them don't have a function. Of course they do. If you stress the organism you can reveal the function. .. If the organism can't make product X by mechanism A, it makes it by mechanism B."

      So it depends a lot on how many mutations it takes to disable an average protein and how much redundancy the human genome has, among other factors. I'm not sure if we have the answers for either of these. As it stands we're not even at the point where we can agree on a deleterious rate.

      Delete
  4. Well, what would the mutation rate have to be to get today's level of diversity with a founding population of Noah's family?

    ReplyDelete
    Replies
    1. Off the top of my head, if two lineages of genes coalesce 10 generations before Noah, and if Noah is about 2304 BC or 4318 years ago, and if 25 years is a generation, the two lineages coalesce about 183 generations ago. The total number of generations from one copy of a gene back to the ancestor, and forward again to the other copy would be 366 generations. We see about one base different every 1000 bases in the genome, when we examine two random copies from the human population. So the mutation rate would be about 0.001/366 or
      2.73 per million per generation.

      Using Larry's higher figure of 160 mutations per generation for the whole genome, and a figure of 2.88 billion bases for the haploid genome size (this is a revised figure I have heard lately -- I am using it to be conservative), we expect 0.0277 per million bases.

      So we need a mutation rate 2.73/0.0277 = 98.55 times higher than today's rate. I have in all cases used figures that make this ratio small, so it is conservative, made as close as possible to 1. But it still is almost 100-fold higher.

      Of course, if two copies today could come from different copies in Adam, as they would about half the time, we would need about half as much mutation so the ratio to today's rates would be closer to 50.

      Delete
  5. Has anyone seen this page? I am not an expert but this guy seems to have done his homework. In discussing it with him, he said that given the rate of deleterious mutations in DNA, evolution can only support a maximum of 2% to 5% of "Strictly Functional" DNA (inclusive of only functions that would fatally impact the DNA). The current consensus (doesn't exist but) seems to be on the order of 20% of DNA is "Strictly Functional". Where is the disconnect between the protein encoding functions and the other functions which would be fatally impacted by a mutation? Please help me understand what I am missing...or this author is missing: http://notascientist.d512.com/worldview/biology/evolution/junk-dna/#Defining-Terminology

    ReplyDelete
    Replies
    1. The current consensus among the experts is that less than 10% of the DNA in your genome is functional.

      Here are some of the other things in a genome.

      What's in Your Genome?

      Here's the genetic load argument.

      A lesson on genetic load

      You link to a website written by a creationist. The title of the website is "Not A Scientist." That should be a clue.

      Delete
  6. Did you guys think JoeCoder's references ware complete hogwash or?

    ReplyDelete
    Replies
    1. Most of his references are valid. The scientific debate over the amount of junk in our genome began more than 50 years ago. It's easy to pick out examples of scientists who support one side or another. The difficult part is to sift through the evidence and the ideas in order to see the big picture. For every reference he gives to support the ID position (no junk DNA) I could give you ten that dispute or refute his authorities.

      His references aren't hogwah. What's hogwash is the references he DOESN'T give you. That, plus his inability to think logically and do simple arithmatic.

      Delete
  7. The link in the Blog is dead...I am trying with all my might to bridge this Gap so that a NON SCIENTIST (in my case Engineer) can understand the causes and effects and it's like a puzzle that nobody has taken the time to unravel...No wonder the ID people get so much attention. They throw very sharp (well elucidated) darts and get curt replies... I am an Atheist and am not a proponent of ID but I suddenly find myself arguing against a bunch of scientists (degreed Scientists) who know a shitload more about this stuff than I do and it is surprisingly difficult to put up any kind of fight without being armed....Thanks for replying to me...I am fighting the good fight...please help me....when you have the time/inclination...

    ReplyDelete
  8. Thank you. So if you think 10% is "Functional" why did you use 2% in another post regarding mutations?

    I am debating this very issue with joecoder at the moment and am struggling. I asked him where his data is and he points to it and you say it ok but proceed to denounce the guy because hes a proponent of ID...You criticized his math but didn't show where it was wrong...I am only focusing on this point...I am not addressing his mutation rates at all... Does the Scientific community have a pretty clear line on how much of the DNA could be fatally effected by mutations? To the point where the DNA drops out...?

    ReplyDelete
  9. About 2% of the human genome codes for protein. About another 6-8% does other important jobs; gene regulation, coding for ribosomes and transfer-RNA, telomeres, centromeres, etc. So using the 2% or 10% value could be true, depending on what you're trying to say.

    See the Sandwalk post "What's in your genome?"

    ReplyDelete
  10. The point of the joe coder blog is a simple one. Deleterious Mutations mean that no more than 5% of our DNA can be effected by the same. If you assume a DM rate of X. It seems two (not very well defined) primary variables are at play: One being the amount of "functional" DNA which can be mutated deleteriously and the second being the rate of deleterious mutation....assuming we know the answer to the first.

    ReplyDelete