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The fine work of Joe Felsenstein and M. Wilson Sayres

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Joe Felsenstein is an evolutionist that has a unique distinction of having his work favorably cited by creationists and bible scholars (except where he disagrees). For example, religious scholars are using Joe’s work to find descendants of the line of priests from the time of the Bible’s King David. See: Y-Chromosomal Aaron.

Joe is also widely credited with coining the phrase “Muller’s ratchet”, a concept articulated in a paper 40 years ago! He must have written that when he was really young, 1973 was a while back.

The wiki entry on Muller’s ratchet:

In evolutionary genetics, Muller’s ratchet (named after Hermann Joseph Muller, by analogy with a ratchet mechanism) is the process by which the genomes of an asexual population accumulate deleterious mutations in an irreversible manner.

In other words, Darwinian evolution doesn’t always clean out the bad, real evolution ensures some of the bad becomes permanent!

Muller’s ratchet actually applies in sexually reproducing creatures if the genetic material has regions like the Y-Chromosome where material is passed off only from father to son. (More on that later as it relates to M. Wilson Sayres recent paper). And my best reading of Joe’s paper suggests that creatures with recombinatorial ability are not immune to getting twisted by problems similar to that of Muller’s ratchet, only that they have a better advantageous defense against it in small populations. So a “ratchet” is universal, just not as deadly in species with the ability to exchange genetic material. Whatever we wish to call it, the “ratchet” problem both in asexual and sexually reproducing species remains.

The paper is Evolutionary Advantage of Recombination .The paper is technical and apologies in advance to Joe if what I state mischaracterizes his position, but I will do my best to explain from my lay perspective.

But first, there is the problem of defining the notions of “deleterious” or “fit” mutations. If we define something as harmful or beneficial based only on the criteria of successful reproduction, we run in to some nasty paradoxes which Andreas Wagner, Lewontin, and others saw clearly. A quasi humorous take of this problem was pointed out in my discussion Survival of the sickest, Why we need Disease and a more technical discussion in Dennett’s strange idea is a bad idea for recognizing biological function . Simply stated, sickness and blindness in the Darwinian world can be viewed as “beneficial” and this leads to problems in defining what is actually “fit”, because the notion of “fit” is fluid. Lewontin pointed out in population genetics the notion of “beneficial” becomes so fluid as to become meaningless. Dennett’s strange idea goes into the details of this problem.

Secondly, because a population could be far sicker than its ancestors but still reproductively “fit” in terms of offspring, the problem of malfunction is equivocated away by “compensatory mutations” which enable more reproductive success but not restoration of function. Thus a population of blind cave fish in a dark cave can be viewed as supremely fit over the cave fish that have functioning eyes. The problem of Muller’s ratchet is alleviated through a process of implicit equivocation (I’m not saying it’s deliberate, but a serious oversight).

With those two caveats regarding the notion of “fit”, it is still helpful to see the effect of Muller’s ratchet. The paper delves into the notion of a bad mutation sweeping through a population and then becoming a feature of the entire population, a process we call fixation. When all the members of the population have the defective gene, the mutation is said to be “fixed”. How can selection fail? To understand the reasons selection can fail, see Gambler’s Ruin Is Darwin’s Ruin.

Problematic is that when this condition happens (where all individuals permanently have the bad mutation), the bad mutation by definition it is now the new baseline, and it ceases to be bad, just like blindness in cave fish. As long as we get some compensatory mutation to improve the number of offspring generated, the problem of lost function is equivocated away by the fluid notions of what it means for a population to be fit.

Joe’s paper goes into the problem of Muller’s ratchet instilling dysfunctional features into all members of population, the main point being that sexually reproducing creatures are better able to resist getting twisted by a ratchet than asexually reproducing creatures.

But Muller’s ratchet understates the problem of bad mutations, since the ratchet only deals with mutations that get fixed into every individual in a population, not ones that are in subsets of the population but are still harmful. Muller’s ratchet says some of the bad mutations become permanent, but another problem is that the number of bad mutations keep increasing even if they are not permanent.

Here is a conceptual cartoon of the problem in asexually reproducing genes. The red dots represent mutations, the broken ginger bread men represent serious expression of the bad gene. The broken ginger bread men are eliminated by selection, some of the bad genes are never purged, they accumulate over time. Humans may be subject to thousands of harmful mutations per individual per generation. The cartoon only uses one mutation per individual per generation to drive its point home.:

http://youtu.be/SrIDjvpx7w4

Muller’s ratchet delves into the likelihood the bad mutants will be “fixed” into a population, but that isn’t even the final problem, the problem is purging the bad mutations that aren’t even fixed. Muller’s ratchet guarantees some mutations will become more or less permanent, but with sufficient numbers of mutations per individual per generation, it is evident the deterioration and dysfunction will eventually become the norm even if Muller’s ratchet doesn’t infuse a given bad mutation into every member of the population. Only by allowing sickness to be redefined as “fit” does the problem really go away on paper.

The idea of Muller’s ratchet inspired creationists to begin investigating the problem of bad mutations. Unfortunately, creationists are not sufficiently recognizing the definitional difficulties that Lewontin realized when trying to define fitness, namely the statistical interpretation of “fit” leads to absurdities such as Survival of the sickest, Why we need Disease.

Regrettably, unlike most of my posts at UD, I don’t feel comfortable in asserting a black and white conclusion that Darwinism is definitely wrong based on Joe Felsenstein’s work (not that he would ever say that either). But Joe, like so many population geneticists (Haldane, Fisher, Crow, Kimura, Nachman, Crowell, Kondrashov, etc.) have a peculiar stature of commanding great admiration from ID proponents and creationists (i.e., Dembski frequently refers to Fisher in favorable terms). The population geneticists have unwittingly inspired creationists with the conviction that life was created.

Finally, I’d like to salute M. Wilson Sayres who reminded me by her published work that the human genome is showing signs of deterioration. This is consistent with findings in different areas of population genetics. See: Sanford’s pro-ID thesis supported by PNAS, read it and weep, literally. I quoted, Michael Lynch in that essay:

Unfortunately, it has become increasingly clear that most of the mutation load is associated with mutations with very small effects distributed at unpredictable locations over the entire genome, rendering the prospects for long-term management of the human gene pool by genetic counseling highly unlikely for all but perhaps a few hundred key loci underlying debilitating monogenic genetic disorders (such as those focused on in the present study).

Thus, the preceding observations paint a rather stark picture. At least in highly industrialized societies, the impact of deleterious mutations is accumulating on a time scale that is approximately the same as that for scenarios associated with global warming—perhaps not of great concern over a span of one or two generations, but with very considerable consequences on time scales of tens of generations.

Michael Lynch

M. Wilson Sayres reported publication of her paper here: Gene Survival and Death on the Y-Chromosome. Her work showed that even on the assumption of evolution, there seems to be substantial deterioration in the Y-chromosome.

In contrast, even without evolutionary assumption, Bryan Sykes at Oxford is noting emergence of irreversible dysfunction in the Y-Chromosome in the present day by comparing fathers to sons to grandsons etc. Sykes wrote the book Adam’s Curse: A future without men (a title that should no doubt be welcomed by the Feminist GNUs and Skepchicks). About the book:

Bryan Sykes follows up The Seven Daughters of Eve with the equally challenging and well-written Adam’s Curse. This time, instead of following humanity’s heritage back to the first women, Sykes looks forward to a possible future without men. The seeds of the book’s topics were sown when Sykes met a pre-eminent pharmaceutical company chairman who shared his surname. Using the Y chromosome, which is passed nearly unchanged from father to son, the author found that he shared a distant ancestor with the other Sykes. Along the way, he discovered that the Y chromosome was worth examining more closely. The first third of Adam’s Curse is devoted to a clear and comprehensive lesson about genetics, the second narrates several fascinating stories of tracing ancestry via the Y chromosome, and the last chapters explore the history of male humanity and its future. Some readers will eagerly skim until they reach Chapter 21, where Sykes gets to the heart of the matter–why and how the Y chromosome has created a world where men overwhelmingly own the wealth and power, commit the crimes, and fight the wars. He uses the structural puniness of the Y chromosome to demonstrate that men are as unnecessary biologically as they are dominant socially. Sykes’ provocative and quite personal book is likely to be unpopular among science readers who prefer their biology divorced from sociology, but his points taken in context will be difficult to refute.

Another relevant study is:
Human Y Chromosome Base-Substitution Mutation Rate Measured by Direct Sequencing in a Deep-Rooting Pedigree.

Dr. Sayres was very kind to respond to my queries at Pandas Thumb. My question was:

Dr. Sayres,

Does your work agree with that of Bryan Sykes at Oxford who asserted that the Y-chromosome is dying quickly. He feels this could lead to extinction in about 100,000 years.

Some have argued that even thought humans reproduce sexually, that Muller’s ratchet applies to Y-chromosomes, and hence it’s unlikely that recovery will happen damaged genes as might be the case where genetic material can be exchanged and mixed from both parents.

Thank you in advance, and congratulations on your publication.

Dr. Sayres responded:

Hi Salvador,

I don’t think that there is clear evidence that the Y will become extinct in 100,000. There are many ways to avoid this. One of which has already occurred on the human sex chromosomes – the addition of a large autosomal segment to both the X and the Y (we call it the X-added or Y-added region). This region is autosomal in marsupials, but sex-linked in eutherian mammals. We have an extra table in the supplement of the paper discussed here that shows that gene loss occurs relatively quickly at first, then seems to slow down. This is consistent with previous work I did looking at substitution rates over evolutionary time in the X/Y-added regions (where we observe that very quickly after recombination is suppressed, the substitution rate increases on the Y, but then it does not continue to increase, at least for the surviving genes).

It is true that Muller’s ratchet applies to the Y chromosomes, but recent work I’m doing now (submitting a revised version in the next few weeks) shows that purifying selection, and specifically background selection, because nearly all of the content on the Y is linked, is quite strong on the human Y chromosome, acting to retain the little content it has left.

But, if we (humans) did “lose” the Y chromosome, we would still survive. The sex-determining region would likely jump to an autosomal chromosome, and the whole wonderful process would start all over again. Or, maybe some other mechanism we haven’t yet anticipated.

Best, Melissa

The issues raised do not have closure, and it is evident there are pointed disagreements on evolution, especially on the efficacy of “purifying selection”. Creationists argue purifying selection will never be sufficient (the cartoon above tries to display in simplest terms why purifying selection must logically fail).

The research and discussions will just have to keep moving forward, and hopefully more clarity will emerge in due time. I’ll just have to leave it at that for now.

Many kind regards to Dr. Felsenstein and Dr. Sayres for their willingness to dialogue.

Comments
by some unproven speculative mechanism of “synergistic epistasis”
Do you even understand what “synergistic epistasis” of deleterious mutations means? It's not some wild, crazy, unproven idea. E.g., pop quiz: is epistasis thought to be common or rare in biology?
It’s true, I didn’t study phylogentics 101, I thought Quantum Mechanics 400 or General Relativity 700 was a more important topic for a bystander to the world of science than studying phylogenetics 101 — phylogenetics, a discipline that has yet to make a conflict-free phylogenetic tree above the trivial for Darwin’s grand claim of Universal Common Ancestry. What were you saying again about phylogenetics passing with flying colors?
I say you don't understand the fact that phylogenetic incongruence has degrees, and typically the degree of observed incongruence is remarkably, amazingly, small -- in a rigorous statistical sense -- given just how big incongruence would be if there were no phylogenetic signal in the data (either genetic, morphological, or both compared with each other). Making the argument you are making about phylogenetics is about as silly as if I argued that various fundamental theories of physics were wrong because various measurements of physical constants disagreed by 0.000001% or whatever. All measurements in science have error. Phylogeneticists know how to measure this and assess the degree of disagreement between independent datasets. You guys have no idea, and instead just cherry-pick and quote-mine from other people who are not statistical phylogeneticists.NickMatzke_UD
May 29, 2013
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Kondrashov's abstract is below. Note, his paper describes mutations that selection can't see. Some of the mutations he describes are approximately in-line with my thesis that the notion of "fit" is suspect if one defines "fit" only by statistics instead of function. If something is functional but will not be selected against when it becomes dysfunctional, it leads to serious problem. We know on mathematical grounds such functions have to exist since the force of selection must be diluted in some proportion by the number of traits (or even nucleotides). The problem of purging out the bad is awful, not just because problems get infused into the population by Muller's ratchet but even non-fixed mutation just linger only to be replaced by other bad mutations.
Abstract It is well known that when s, the selection coefficient against a deleterious mutation, is below approximately 1/4Ne, where Ne is the effective population size, the expected frequency of this mutation is approximately 0.5, if forward and backward mutation rates are similar. Thus, if the genome size, G, in nucleotides substantially exceeds the Ne of the whole species, there is a dangerous range of selection coefficients, 1/G < s < 1/4Ne. Mutations with s within this range are neutral enough to accumulate almost freely, but are still deleterious enough to make an impact at the level of the whole genome. In many vertebrates Ne approximately 10(4), while G approximately 10(9), so that the dangerous range includes more than four orders of magnitude. If substitutions at 10% of all nucleotide sites have selection coefficients within this range with the mean 10(-6), an average individual carries approximately 100 lethal equivalents. Some data suggest that a substantial fraction of nucleotides typical to a species may, indeed, be suboptimal. When selection acts on different mutations independently, this implies too high a mutation load. This paradox cannot be resolved by invoking beneficial mutations or environmental fluctuations. Several possible resolutions are considered, including soft selection and synergistic epistasis among very slightly deleterious mutations.
Nonetheless Nick asserts:
This is why creationists are a scientific joke and will never be taken seriously.
Nick could of course offer his superior learning of phylogenetics to quell the questions that Kondrashov has raised. It is irrelevant that I may not know much, what is relevant is DarwinDefender's like Nick don't have answers to such basic problems. And even more basic than Kondrashov's problem, has he resolved Lewontin's problem regarding the fluid nature of the meaning of "fit"? That problem was enough for Stanley Salthe to quit defending Darwinism.
Why should I take you seriously when you have basic misunderstandings that would get you failed in phylogenetics 101?
It's true, I didn't study phylogentics 101, I thought Quantum Mechanics 400 or General Relativity 700 was a more important topic for a bystander to the world of science than studying phylogenetics 101 -- phylogenetics, a discipline that has yet to make a conflict-free phylogenetic tree above the trivial for Darwin's grand claim of Universal Common Ancestry. What were you saying again about phylogenetics passing with flying colors?scordova
May 29, 2013
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Why should I take you seriously when you have basic misunderstandings that would get you failed in phylogenetics 101?
You shouldn't take me seriously. :-) But you should take the problems of the theories of evolutionism very seriously, and the problems are legion.
Better yet, read his book, “Inferring Phylogenies”.
Joe Felsenstein is a fine scientist, I've never argued otherwise. Dr. Sayres is too. You're pretty sharp yourself, I just don't share every idea you all subscribe to. But since you're here, Nick, the substance of my objection can essentially be distilled in this peer-reviewed paper by Kondrashov: Why Haven't we died 100 times over Kondrashov didn't answer the question himself except some by some unproven speculative mechanism of "synergistic epistasis". The problems articulated by Konrashov are not over come by the mechanisms Dr. Sayres mentioned. I appreciate her kind and cordial response, and I'm sorry that I disagree with her since she's a lot nicer to me than you are.scordova
May 29, 2013
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That conclusion by Dr. Sayres was derived by an evolutionary assumption, it is an inference, but not direct observation.
Says the young-earth creationist who believes YEC in spite of the evidence, and who ignores that common ancestry and phylogenetic methods can be tested, have been tested, and have passed with flying colors. Ask Joe Felsenstein, he'll tell you the same thing. Better yet, read his book, "Inferring Phylogenies". I read it for my qualifying exam. Why should I take you seriously when you have basic misunderstandings that would get you failed in phylogenetics 101?NickMatzke_UD
May 29, 2013
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NickMatzke_UD, That conclusion by Dr. Sayres was derived by an evolutionary assumption, it is an inference, but not direct observation. Whereas, the deep pedigree study is very close to real-time evidence of what happens also Michael Lynch and Bryan Sykes work is real-time (in the present day) versus what is derived from evolutionary assumptions.
This is why creationists are a scientific joke and will never be taken seriously.
My my, this post is getting under your skin. :-) So what if we're never taken seriously, do you think evolutionary biology has much real rank in science except token homage?
In sciences pecking order, evolutionary biology lurks somewhere near the bottom, far closer to phrenology than to physics. Jerry Coyne
Thanks for you comments Nick.scordova
May 29, 2013
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Hmm. Scientists find: Conversion of autosomes to sex chromosomes, followed by decay of one of the sex chromosomes, followed by the sex determining genes jumping to another chromosome (or the decayed chromosome fusing onto an autosome), has happened again and again in evolution, in many different lineages over millions of years. Sal concludes: Humans can only last thousands of years and evolution is wrong. Me: This is why creationists are a scientific joke and will never be taken seriously.NickMatzke_UD
May 29, 2013
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