Intro by Jerry: One of the pillars of neo-Darwinian evolution is the assumption, supported by a great deal of evidence, that mutation is “random.” This does not mean that mutations occur with equal frequency everywhere in the genome (they don’t), that different genes have the same mutation rate (they don’t), or that even within a gene some mutations don’t occur more often than others (they do). Rather, the statement that “mutation is random” means that the likelihood of a mutation occurring does not depend on whether in a given situation it would be advantageous or deleterious.
The idea that mutations are “nonrandom”—usually meaning that adaptive mutations are more likely to occur in some situations (e.g., a change in environment)—has been bruited about for years, mainly because if this was a fairly common phenomenon, it would create a substantial rethinking of the neo-Darwinian theory of evolution. But there is no way we know of that the frequency of an error in the DNA sequence, which is what a mutation is, can be elevated in the adaptive direction when the environment changes. (We know that environmental changes can raise the overall mutation rate, but this is not an adaptive phenomenon because the vast majority of mutations are harmful.) Because of this lack of evidence for “adaptive mutation,” and the absence of a mechanism whereby it could occur, evolutionists continue to accept that mutations are “random” in the sense I defined.
Recently, a paper appeared that seemed to show that at least one mutation in human hemoglobin—the one causing sickle-cell anemia when present in two copies—could occur more frequently in areas where the mutation is adaptive: malaria-ridden areas of Africa. The sickle-cell mutation, as Brian Charlesworth shows below, is adaptive, but only when present in one copy, when, together in a “heterozygote” with one copy of the “normal” hemoglobin beta chain, it confers substantial protection against malaria. The heterozygote has higher survival and reproductive fitness than either the homozygote for the ‘normal’ allele, which is more prone to fatal malaria, and the sickle-cell homozygote, which has the disease sickle-cell anemia and is prone to die before adulthood. The mechanics of population genetics show that if a heterozygote with one copy of each of two alleles has higher reproductive ability (read “survivorship” here) than either of the two homozygotes, it will be maintained in the population at a stable equilibrium frequency, regardless of how bad off the homozygotes are. The sufferings of those with sickle-cell anemia can be seen as the price paid because of the higher malaria resistance of heterozygotes carrying only one copy of the gene. It also shows that evolution doesn’t create the optimum situation: that would be a single mutation that causes malaria resistance when present in either one or two copies.
This, by the way, explains why African-Americans are more prone to sickle-cell anemia than people from other populations, for they still carry the “HbS” mutation prevalent in their ancestors who were brought to America as slaves. The frequency of the HbS mutation in the U.S., however, is now falling, and for two reasons: we don’t have malaria in the U.S., which is necessary to keep the gene at an equilibrium frequency, and because African-Americans have intermarried with whites, who don’t carry copies of HbS. Eventually, prenatal testing and genetic counseling will be able to eliminate sickle-cell anemia, and the HbS allele, completely.
At any rate, the paper, by Melamed et al. (reference below), appeared to show that the mutation rate from the “normal” DNA sequence to the HbS “sickle-cell” sequence was higher in Africans than in Europeans. This was quickly picked up by the popular press as an example of “adaptive mutation” and as a refutation of modern evolutionary theory. (The “Darwin Was Wrong” trope still sells newspapers, especially in America!) Many readers wrote me and asked me about this paper, which I hadn’t yet read, but I told them that a better analysis was in the works.
I pointed this out to my friend, colleague, and ex-chairman (at Chicago) Brian Charlesworth, one of the world’s premier evolutionary geneticists. He quickly spotted the error in the Melamed et al. paper that refuted its conclusion of “adaptive mutation,” but was too busy to refute it on paper. After I kept hectoring him to write something up since the “Darwin was wrong” trope was associated with this paper in many articles in the popular press, he finally deigned to write a short and sweet refutation. Rather than submit it as a rebuttal to the journal (he said he has two refutations of other papers in press, and doesn’t want to get a reputation as a debunker), Brian allowed me to publish the rebuttal here. I’ve put it between the lines below.
Note that the error in Melamed et al. stems from a flaw in the assumptions: that all the new mutations analyzed were independent.
No evidence for an unusually high mutation rate to an adaptive variant
Brian Charlesworth
Institute of Evolutionary Biology
School of Biological Sciences
The University of Edinburgh
Edinburgh, UK
The hemoglobin S variant (HbS) causes the near-lethal sickle cell disease when homozygous (present on both the maternal and paternal chromosomes) and confers protection against malaria when heterozygous (present on either the maternal or paternal chromosome). The HbS variant exists at substantial frequencies in several populations in Africa, as well as in Arabia and India. It is the classic example of heterozygote advantage, whereby a mutation that increases the fitness of its heterozygous carriers cannot replace its alternative because of the loss of fitness to homozygotes. (Note that 2022 is the 100th anniversary of R.A. Fisher’s discovery of how this process works). The HbS mutation is a single change from adenine to thymine at the sixth amino acid position in the beta globin gene, resulting a change in the amino-acid in the corresponding protein for valine to glutamic acid (it was the first mutation to be identified as causing a change in the sequence of a protein). Studies of the DNA sequences of chromosomes carrying the HbS mutation show that there are five major classes of sequences associated with it, but recent analyses show that the mutation probably arose only once, followed by recombination events that placed it onto different genetic backgrounds. This provides a classic example of what is known as a “partial selective sweep”, in which a new mutation with a selective advantage arises on a single genetic background, so that variants present on this background spread through the population in association with it.
Melamed et al. (2021) claim to have evidence that challenges the standard neo-Darwinian view that natural selection acts on mutations that arise “randomly”, i.e., without reference to their effects on the survival or fertility of their carriers (indeed, most mutations with noticeable effects reduce the fitness of their carriers). The evidence for Melamed et al.’s claim comes from an experiment in which the authors applied a novel technique for identifying new mutations in millions of sperm cells. With regard to the detection of HbS mutations, they characterized sperm from 7 African and 4 European men. They observed 9 instances of the HbS mutation in the sperm of Africans and none in the Europeans. They pointed out that HbS is at a selective advantage in Africans but not in Europeans, and suggested that the seemingly higher mutation rate is the result of a hypothetical process proposed by Adia Livnat, a co-author of the paper, whereby “adaptations and mutation-specific rates jointly evolve”. This claim has been disseminated in the media as evidence against the neo-Darwinian view of selection on random mutations [JAC: see below for some of these media references]– here it is claimed that mutations that are selectively advantageous in a particular environment arise more frequently than in environments where they lack an advantage.
However, there is no statistical support for the claim that there is a higher mutation rate to HbS in African men. While the authors looked at very large number of sperm, these came from only 11 individuals. Five of the nine HbS mutations occurred in a single individual, and 2 other individuals contributed 2 mutations each. The events within individuals cannot be treated as independent of each other, because there is a large population of dividing cells that are precursors of the mature sperm. If a mutation occurs in a cell that gives rise to several sperm after a number of divisions, there will be several copies of the mutation in the sperm pool. This is the cause of the well-established fact that the frequencies of mutations in human sperm increase with the man’s age. If we treat each individual as a single observation, we have 3 cases of HbS mutations among 7 Africans and 0 among 4 Europeans. Fisher’s exact test shows that the difference between Africans and Europeans has a probability of about 11% of arising by chance in the absence of any true difference.
There are other reasons for doubting this claim. First, it is exceedingly hard to see how there could be any biological process that could cause the HbS mutation to have a higher mutation rate in order to allow Africans to evolve malaria resistance, which is thought to have become a significant selective factor at most around 20,000 years ago. Mutations arise as errors in the replication of DNA molecules or as the result of damage to non-replicating molecules. There is no known mechanism whereby an organism could devise a process that would allow it to produce one specific class of mutation at a higher-than-average frequency just when that mutation is at an advantage. Further, the genetic evidence referred to above suggests that the HbS variant prevalent in human populations traces its ancestry back to a single ancestral mutation (Shriner and Rotimi, 2018; Laval et al., 2019) , so that there is no reason to believe that a high mutation rate has enabled multiple copies of the mutation to spread.
References
D. Melamed et al. 2022. De novo mutation rates at the single-mutation resolution in a human HBB gene region associated with adaptation and genetic disease. Genome Research 32:1-11. Free pdf here.
D. Shriner and C. N. Rotimi. 2018. Whole-genome-sequence-based haplotypes reveal single origin of the sickle allele during the Holocene wet phase. Am. J. Hum. Genet. 102:547-556.
G. Laval et al. 2019. Recent adaptive acquisition by African rainforest hunter-gatherers of the late Pleistocene sickle-cell mutation suggests past differences in malaria exposure. Am. J. Hum. Genet. 104:553-561.
Among the many popular articles that cite Melamed et al. as a rebuttal of modern evolutionary theory, see here, here, here, here, here, ad infinitum:
Two examples (click on screenshot)s:
And here’s Brian:
Great topic. Always worth reviewing.
I always love an evolution post, thank you!
Brian, thank you very much, your critique is excellent and I hope your points will be noted and reported by the popular press. I for one would vote for you to change your mind and submit this as a rebuttal to the journal, which action would most likely elicit press coverage. I think being a debunker is a noble calling, and an essential one in the field of Evolution.
Jerry, you have a gift for making things clear and simple to a less professional reader. I doubt that a lay reader would be able to identify the specific refutation in Brian’s statement. I’m pretty sure it’s citing the 11% probability of the outcome occurring by chance, it could also be pointing out the minuscule sample size, but in any case I doubt a reporter or an editor would notice or understand the significance of either.
I remember that paper! There was a chart in it showing the results, with subjects on the y axis and a list of various mutations across the x. From what I recall, yeah it did look like an “if you threw random darts at this dart board, you could get this result” set of results. Reinforcing the old adage that random distribution of results /= even distribution of results.
Philosophically it is difficult to see how adaptive mutation is possible; that would require some aspect of an organism’s future developmental chemistry to affect the chances of a mutation occurring in it’s past parent’s sperm or egg genome. Doesn’t seem like there’s any rational mechanism for that.
It does however seem possible (and would NOT be any sort of “Darwin was wrong” mechanism) for there to be some sort of secondary or knock-on effect which might look a bit like this. Population A could, because of it’s environment, evolve to have a higher mutation rate (either whole genome or in a specific region) than Population B living somewhere else. In that case we would expect A to show higher rates of both positive and negative mutations (either across the genome or in the region). That would not undermine Darwinian evolution…but if a scientist (foolishly) only tracked a small subset of positive ones, they could erroneously conclude that population A was producing more of them.
Yes, but you’d have to explain why, since it’s deleterious, a population would evolve to have a higher mutation rate in general, since most mutations are harmful. That WOULD undermine Darwinian evolution. And why would the population evolve to have a higher mutation rate in a “specific region” of the genome?
In general yes. In (I’d say) fairly extreme cases it is possible for selection to favour an increase in mutation rates. If selection is sufficiently strong, mutations that themselves increase the mutation rate (beneficial and deleterious) can hitchhike along with some of the beneficial mutations they caused (for example https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1462288/). Of course, in the long term selection will decrease mutation rates again (because most mutations are deleterious). So there is only a short-term spike in mutation rate. This is all completely darwinian though. And it will only work in organisms with little or no sex, as otherwise the linkage between the two mutations will be broken and there will be no hitchhiking.
Yes, it is possible, as you say, but then the mutation rate goes down again, and I know of only this single case in the asexually reproducing E. coli.
I’ll give you one two real cases and one hypothetical about how different populations could show different variability. But just to repeat, none of these support adaptive mutation. They just give examples of how one subpopulation of organisms can show a greater genetic variability or mutation rate than another subpopulation of the same species.
First, it is factually true that different regions of the Earth have different background radiation rates. It varies by up to a factor of 10, IIRC. If you live at higher elevation, higher background. Got a lot of uranium and thorium in your soil, higher background. Whether this affects mutation rate has been researched, but results are not definitive. From what we know about radiation and mutation, it is certainly within the realm of ‘a reasonable hypothesis’ for this to lead to subpopulations with higher mutation rates. For the sci-fi fans, think some future space or mars colony; given the *much* higher cosmic ray background for such colonies, I would say it is likely such a subpopulation would have a higher mutation rate. What do readers think? Do they agree with that hypothesis?
Second actual case: some single-celled organisms (maybe prokaryotes? I don’t think eukaryotes do this) prefer cloning but switch to sexual reproduction under environmental stress. That’s a way of inducing a higher variability. Which is not mutation rate but shows how bog-standard normal Darwinian evolution does not rule out the evolution of organisms that have different variability.
Third, theoretical case: how could a different mutational rate evolve in a subpopulation of humans (or other higher organisms that only reproduce via sex)? Well we have DNA-repair mechanisms…which are also constructed during development, from DNA instructions. So if a mutation in the sequences that create DNA-repair function caused it to work less effectively, and for some sub-population that was adaptive, then that mutation could spread through that subpopulation. But it wouldn’t exist in other subpopulations. So after a while you’d see that that one subpopulation had a higher mutation rate.
As for why or when that sort of change would be adaptive, I will swag here and say that based on the single-celled case above, there seems to be some indication that in a stable ecosystem “less variability” may be adaptive while in unstable or stressful ecosystems, “more variability” may be more adaptive. So a hypothetical mutation that allowed more mutations “past the goalie” of our DNA repair mechanisms might, in theory, be adaptive in relatively unstable environments.
That’s a hypothetical…and two actuals that don’t apply to the case of African sickle-cell anemia. For the case mentioned in the article, I’m fully on board with Prof. Charlesworth.
Yet another case of poor refereeing. Standards really have fallen and if such a statistical howler can be spotted by a reader then the referees should be utterly ashamed of themselves for not spotting it.
Referees – you get what you pay for.
(Most refereeing work is unpaid.)
One journal that did pay, albeit nominally, was European Journal of Biochemistry, and its successor FEBS Journal. We were paid once/yr, if we had reached a certain threshold, which I guess had the effect of getting reviewers to handle a larger load. The other nice thing about that was that they send all (usually three) reviewers copies of what they had all written, which let us see what the others had focused on etc., along with the editor’s decision.
And once that actually allowed me to rescue a paper that I had really liked, but that was rejected for what I considered wrong reasons. I wrote to the editor and he reversed his decision!
Very good. The claim would require a far larger sample size of different individuals, since it would amount to testing for a rather slight but statistically significant ‘nudge’ in mutation frequency. One should wonder how this problem got past the reviewers.
Even if it were to hold up (that an A to T transversion mutation at this locus is slightly more frequent in African populations), it seems to me it would fall under the ambit that there are regions with higher mutation rates anyway.
Which reminds me of this other paper making the rounds which claims that in the plant Arabidopsis, mutations are markedly less frequent in genes than elsewhere, and they are even less frequent in essential genes. This was discussed recently in Panda’s Thumb here: http://pandasthumb.org/archives/2022/03/are-mutations-random.html#disqus_thread.
I honestly can’t make heads or tails of most of the paper, as it is very technical to me.
Perhaps this is a common Americanism but
“resulting a change in the amino-acid in the corresponding protein for valine to glutamic acid”
seems confusing to me (I’m Irish).
The sickle celled version of the protein has valine instead of glutamic acid. (The non-polar nature of valine is what explains the tendency of the globin to precipitate).
Shouldn’t this read “resulting (in) a change in the amino-acid in the corresponding protein TO valine FROM glutamic acid”?
Brian is British.
Jerry, it seems you only addressed the grammatical ‘in’ part, not the technical ‘valine to glutamic acid’ part. Comment 9 suggests the same thing as Liam as regards this technical back to front.
However, on the ‘in’ part, we (I’m British too), as far as I’m aware, do not omit ‘in’ within the context of the given example as context. “resulting a change” absolutely is an omission of ‘in’ where we would use it.
It’s the job of the writer of the post to correct the scientific errors, not me. You do know that I didn’t write the part you’re talking about, don’t you? It’s a glutamic acid to valine substitution, as far as I remember.
Why on earth are you addressing this to me, though?
Yes, I know you didn’t write the explanation in question. As the website owner, including the comment section, I think that’s grounds enough to address queries regarding the content to you. I think moreso given it’s your field too and you therefore may well be able to address it with authority.
As to “Why on earth are you addressing this to me, though?”, in addition to the above, well, the other part regarded a point that you did respond to (the grammar). Again,I think that’s grounds enough to comment on your response!
I’m sure that climate change will bring malaria back to the southern parts of the USA in fairly short order. I hear occasional reports of malarious mosquitoes being found in southern Spain and Italy, so it’s a fairly good chance that they’ll come north from Central America to the southern States to return the country to the 19th century state of Fundamentalist ignorance and disease so beloved of the religious.
Aren’t there some sickle-cell like blood disorders selected for in the “white” (or not-so-white, by some bigoted humanoids’ opinions) populations of some Mediterranean islands? Ah, but of course – they most likely are different mutations with similar effects, so unlikely to constructively (or destructively) interact with the genes from sub-Saharan Africa.
Have any of the Archaic DNA datasets (Neanderthal, Denisovan) come up with HbS mutations? Which would suggest that the original mutation preceded the (sub-) speciation event that led to these human lineages? Or are we looking at a mutation that occurred in the H.sapiens sapiens lineage after the differentiation into AMH (Anatomically Modern Human), Neanderthal and Denisovan lineages?
Did the paper record information about those individual’s ages? Very prone to the “statistics of small numbers” error highlighted here, but there’s a good chance that the individual with 5 HbS mutations is older than the individuals with two mutations each. Of course, that’s assuming that they inspected roughly similar numbers of sperm from each individual.
It’s a bit of a sideways lurch, but as we are thinking about mutations, I thought I’d just mention the new paper on how quantum mechanics may explain why DNA can spontaneously mutate that is summarized here: https://phys.org/news/2022-05-quantum-mechanics-dna-spontaneously-mutate.html.
Just a quick technical note, Brian has the substitution backwards:
resulting a change in the amino-acid in the corresponding protein for valine to glutamic acid
It is the other way around. HbS is the one with valine at position 6 while the normal HbB has a glutamic acid residue (as first documented by Vernon Ingram in 1956)..
The valine affords greater hydrophobicity to that region of the molecule, enabling aggregation through hydrophobic interactions, which helps defeat the malarial parasite but causes problems in the microcirculation.
https://www.sciencedirect.com/topics/medicine-and-dentistry/hemoglobin-s
50 years ago, Richard Lewontin referred to “the tired old Bucephalus of sickle cell anemia”, at that time the only well documented case of a heterozygous fitness advantage. I guess old horses never die. Seriously, thanks to Jerry and Brian for taking on this point and discussing it in such a clear and accessible manner. Were I still teaching Evolution, I would use the first paragraph of Jerry’s post as either a clicker or a multiple choice exam question.
It is is easy to be wise after an expert has elucidated the subject but I’d like to think that I would have realised that the fact that most of the mutations were found in sperm from the same individual seriously undermined the conclusions drawn in the study. It is rather horrifying that this poor statistical analysis remained unchallenged all the way through to publication.
Yeah, I agree. I hadn’t heard of this study before but if I had looked at it and seen that the number of subjects was so tiny, and then on top of that a significant percentage of the mutations came from a single individual’s sperm, even I (non-expert) would have recognized that as almost certainly being a big problem.
Agreed. An 11% chance of being just coincidence does not confer any confidence. For how many mutations, other than HbS, has this been explored?
If you do 20 types of tests and one comes out ‘significant’ (5%chance of coincidence) you can rest assured that the results are false.
And the other shortcoming is indeed that there is no mechanism proposed or imagined.
The only way I can imagine is that there has been mutation in, and selection for, some ‘regulator genes’ that allow for higher frequency of mutations in some areas. But that would still be random mutation and not so random selection. A kind of meta-selection. All this is hypothetical of course.
Ken are you going woke? You make it sound if all sexual relations between black slave women and their white masters were rape. Were they? Did Thomas rape Sally?
Don’t get me wrong, many of them were rape, but I would not exclude the possibility of a mutual fondness, or other more ‘mercantile’, mutually advantageous, processes. A black slave having sexual relations with her white ‘master’ might have something to gain, eg working in the house instead of in the field. If that was her idea, I’d not call that rape.
Where one of the parties to such an assignation is the chattel property of the other, I’d not call it “consensual” either, Nicky.
I don’t think one need be “woke” to accept that — though if “woke” one need be, I’ll not abandon my contention for fear of the label.
Modern concepts of consent, where consensual sex between a professor and a college student is prosecuted as rape, seem difficult to apply to a now-abolished owner-chattel relationship from the 18th century. (I’m sticking with the 18th because they were the formative years of the Founding Fathers now being defenestrated for owning slaves.). Chattels are bound to obey. That’s the whole point of having them. You don’t respect your horse’s initial refusal to accept a bridle and saddle. You just keep training him until he submits.
Because the definition of what constitutes rape has changed so much in our lifetimes, a slave-owner who had sex with his slaves I think would have to be judged by his contemporaries (and his wife) as to whether this conduct was to be encouraged, winked at, or condemned. You even have to be careful how you regard force. It was only in living memory that a man could no longer lawfully force himself on his wife. Would we expect chattels to have more rights here than a wife? Did they? It might “be rape” to us today but what was it back then? More than just one more abomination of slavery?
Perhaps the outrage over slave owners having non-marital sexual licence with the women they owned on the estate was another motivator of the abolitionist movement. Once you stop seeing people as chattels a lot of behaviour becomes unsupportable and then unimaginable once it’s abolished.
By the laws of the day slave owners who had sex with their slaves may have been guilty of nothing at all but it seems to be a peculiar kind of sophistry to suggest that we cannot therefore call it rape from our modern perspective. The fact that female slaves had no ownership of their own bodies or ability to withhold consent to sexual advances from their owners was far from being the only abhorrent aspect of slavery but it was certainly one such aspect that we are right to condemn whether or not it was legally acceptable at the time. Laws on rape have changed over time but I suppose that being forced to have sex against your wishes was as traumatic in the 18th century as it is in the 21st.
Well yes. As I said, this type of sexual licence that slave owners could enjoy is yet another reason to abolish slavery. Which we did. Twice. But the slave owners themselves are now long dead. It is sophistry to imagine that we can now interrogate Thomas Jefferson about whatever caused him to think that his arrangement with Sally wouldn’t make him guilty of rape…and when he offers no defence—being dead—you can topple his statues.
We go through this in Canada. Our first Prime Minister is today judged by some to have been insufficiently supportive of present-day aspirations of Indigenous people, which seem to be to take all the land back but still draw all their sustenance in idleness from the Canadian state. Macdonald supported and tried to bring about their assimilation into Canadian society as being preferable to leaving them on the Plains to starve as Canada advanced west. But today assimilation is considered deeply, offensively unredeemably racist and so MacDonald has been pretty much cancelled, sometimes violently, from popular memory in the name of reconciliation.
If I’m going to cut our dead guys some slack, common courtesy dictates I do the same for yours.
But no-one on this thread has suggested cancelling Jefferson or offered any speculation regarding his moral reasoning with respect to his relations with his female slaves. Ken was accused of going woke for suggesting that many black slave women were raped by white masters, a contention I would have thought few would argue with.
No-one has a problem now describing slavery as an abomination even though it was perfectly legal back in the 18th century. I am puzzled, therefore, as to why you feel it is necessary to erect a legalistic defence of the rape of black women within the context of slavery. Whether or not the conduct of a slave master who had sex with his slaves was viewed at the time as ‘something to be winked at’ does not oblige us to see it in the same way. We rightly do not retrospectively prosecute people for acts that preceded a change in the law but that does not mean that we cannot consider those acts morally reprehensible (that after all is one reason why we change the law from time to time).
I saw the Melamed et. al. paper last winter, and wrote as follows about it to another
retired geneticist friend .
” A couple of points about sampling make me wonder. First, of course, is that the
sperm samples come from only 4 individual European and 7 African donors, which
might mean that variables other than the donors’ continents could be involved. [In
this connection, 5 of the 9 HbS mutations are in the sample from a single African
donor (who also contributed 11 in-frame dels at a nearby site.] The authors’ give
complex arguments against clonality here, but their arguments are beyond me. ”
I still don’t understand the authors’ arguments for the independence of the HbS mutations,
and Charlesworth doesn’t take them up. Could be informative to do so.
Even if the claim were true, it would sound like an exception proving the rule, in the manner in which claims about epigenetic phenomena tend to do, not the collapse of Darwinism.
Score before this “discovery”: Darwinism 20,000, Non-Darwinism 0
After the “discovery”: Darwinism 19,999 Non-Darwinism 1
That’s not really what the claim “challenges neo-Darwinism” implies. It’s a lot of hype.
What about the ‘Evolution of Evolvability’? Nothing particularly ‘Un-Darwinian’ about it, as far as I can tell.
E.g., See here:
Nat Rev Genet. 2019 Jan;20(1):24-38. doi: 10.1038/s41576-018-0069-z.
The causes of evolvability and their evolution
Joshua L Payne, Andreas Wagner
https://pubmed.ncbi.nlm.nih.gov/30385867/
A belated PS on this discussion: ‘Most ‘silent’ genetic mutations are harmful, not neutral’ – https://phys.org/news/2022-06-silent-genetic-mutations-neutral-broad.html#google_vignette.
An enormous thanks for this incisive and fair critique that will save hours for many of us. Livnat gave an online talk yesterday at Evolution 2022 that made extraordinarily grand claims that his finding requires major revisions basic evolutionary theory…and his warm thanks to the Templeton Foundation.