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Friday, November 09, 2018

Celebrating 50 years of Neutral Theory

The importance of Neutral Theory and Nearly-Neutral Theory cannot be exaggerated. It has radically transformed the way experts think about evolution, especially at the molecular level. Unfortunately, the average scientist is not aware of the revolution that took place 50 years ago and they still think of evolution as a synonym for natural selection. I suspect that 80% of biology undergraduates in North American universities are graduating without a deep understanding of the importance of Neutral Theory.1

The journal of Molecular Biology and Evolution has published a special issue: Celebrating 50 years of the Neutral Theory. The key paper published 50 years ago was Motoo Kimura's paper on “Evolutionary rate at the molecular level” (Kimura, 1968) followed shortly after by a paper from Jack Lester King and Thomas Jukes on "Non-Darwinian Evolution" (King and Jukes, 1969).

The special issue contains reprints of two classic papers published in Molecular Biology and Evolution in 1983 and 2005. In addition, there are 14 reviews and opinions written by editors of the journal and published earlier this year (see below). It's interesting that several of the editors of a leading molecular evolution journal are challenging the importance of Neutral Theory and one of them (senior editor Matthew Hahn) is downright hostile.
Kimura, M. (1983) Rare variant alleles in the light of the neutral theory. Molecular Biology and Evolution, 1:84-93. [doi: 10.1093/oxfordjournals.molbev.a040305]
Based on the neutral theory of molecular evolution and polymorphism, and particularly assuming "the model of infinite alleles," a method is proposed which enables us to estimate the fraction of selectively neutral alleles (denoted by Pneut) among newly arisen mutations. It makes use of data on the distribution of rare variant alleles in large samples together with information on the average heterozygosity. The formula proposed is Pneut = [He/(1-He)] [loge(2nq)/n alpha (x less than q)], where n alpha(x less than q) is the average number of rare alleles per locus whose frequency, x, is less than q; n is the average sample size used to count rare alleles; He is the average heterozygosity per locus; and q is a small preassigned number such as q = 0.01. The method was applied to observations on enzyme and other protein loci in plaice, humans (European and Amerindian), Japanese monkeys, and fruit flies. Estimates obtained for them range from 0.064 to 0.21 with the mean and standard error Pneut = 0.14 +/- 0.06. It was pointed out that these estimates are consistent with the corresponding estimate Pneut(Hb) = 0.14 obtained independently based on the neutral theory and using data on the evolutionary rate of nucleotide substitutions in globin pseudogenes together with those in the normal globins.

Nei, M. (2005) Selectionism and neutralism in molecular evolution. Molecular Biology and Evolution, 22:2318-2342. [doi: 10.1093/molbev/msi242]
Charles Darwin proposed that evolution occurs primarily by natural selection, but this view has been controversial from the beginning. Two of the major opposing views have been mutationism and neutralism. Early molecular studies suggested that most amino acid substitutions in proteins are neutral or nearly neutral and the functional change of proteins occurs by a few key amino acid substitutions. This suggestion generated an intense controversy over selectionism and neutralism. This controversy is partially caused by Kimura's definition of neutrality, which was too strict (|2Ns|≤1).
If we define neutral mutations as the mutations that do not change the function of gene products appreciably, many controversies disappear because slightly deleterious and slightly advantageous mutations are engulfed by neutral mutations. The ratio of the rate of nonsynonymous nucleotide substitution to that of synonymous substitution is a useful quantity to study positive Darwinian selection operating at highly variable genetic loci, but it does not necessarily detect adaptively important codons. Previously, multigene families were thought to evolve following the model of concerted evolution, but new evidence indicates that most of them evolve by a birth-and-death process of duplicate genes. It is now clear that most phenotypic characters or genetic systems such as the adaptive immune system in vertebrates are controlled by the interaction of a number of multigene families, which are often evolutionarily related and are subject to birth-and-death evolution. Therefore, it is important to study the mechanisms of gene family interaction for understanding phenotypic evolution. Because gene duplication occurs more or less at random, phenotypic evolution contains some fortuitous elements, though the environmental factors also play an important role. The randomness of phenotypic evolution is qualitatively different from allele frequency changes by random genetic drift. However, there is some similarity between phenotypic and molecular evolution with respect to functional or environmental constraints and evolutionary rate. It appears that mutation (including gene duplication and other DNA changes) is the driving force of evolution at both the genic and the phenotypic levels.

Kumar, S., and Patel, R. (2018) Neutral Theory, Disease Mutations, and Personal Exomes. Molecular Biology and Evolution, 35:1297-1303. [doi: 10.1093/molbev/msy085]
Genetic differences between species and within populations are two sides of the same coin under the neutral theory of molecular evolution. This theory posits that a vast majority of evolutionary substitutions, which appear as differences between species, are (nearly) neutral, that is, these substitutions are permitted without a significantly adverse impact on a species’ survival. We refer to them as evolutionarily permissible (ePerm) variation. Evolutionary permissibility of any possible variant can be inferred from multispecies sequence alignments by applying sophisticated statistical methods to the evolutionary tree of species. Here, we explore the evolutionary permissibility of amino acid variants associated with genetic diseases and those observed in personal exomes. Consistent with the predictions of the neutral theory, disease associated amino acid variants are rarely ePerm, much more biochemically radical, and found predominantly at more conserved positions than their non-disease counterparts. Only 10% of amino acid mutations are ePerm, but these variants rise to become two-thirds of all substitutions in the human lineage (a 6-fold enrichment). In contrast, only a minority of the variants in a personal exome are ePerm, a seemingly counterintuitive pattern that results from a combination of mutational and evolutionary processes that are, in fact, broadly consistent with the neutral theory. Evolutionarily forbidden variants outnumber detrimental variants in individual exomes and may play an underappreciated role in protecting against disease. We discuss these observations and conclude that the long-term evolutionary history of species can illuminate functional biomedical properties of variation present in personal exomes.

Austerlitz, F., and Heyer, E. (2018) Neutral Theory: From Complex Population History to Natural Selection and Sociocultural Phenomena in Human Populations. Molecular Biology and Evolution, 35:1304-1307. [doi: 10.1093/molbev/msy067]
Here, we present a synthetic view on how Kimura’s Neutral theory has helped us gaining insight on the different evolutionary forces that shape human evolution. We put this perspective in the frame of recent emerging challenges: the use of whole genome data for reconstructing population histories, natural selection on complex polygenic traits, and integrating cultural processes in human

Niida, A., Iwasaki, W.M., and Innan, H. (2018) Neutral Theory in Cancer Cell Population Genetics. Molecular Biology and Evolution, 35:1316-1321. [doi: 10.1093/molbev/msy091]
Kimura’s neutral theory provides the whole theoretical basis of the behavior of mutations in a Wright–Fisher population. We here discuss how it can be applied to a cancer cell population, in which there is an increasing interest in genetic variation within a tumor. We explain a couple of fundamental differences between cancer cell populations and asexual organismal populations. Once these differences are taken into account, a number of powerful theoretical tools developed for a Wright–Fisher population could be readily contribute to our deeper understanding of the evolutionary dynamics of cancer cell population.

Cannataro, V.L., and Townsend, J.P. (2018) Neutral Theory and the Somatic Evolution of Cancer. Molecular Biology and Evolution, 35:1308-1315. [doi: 10.1093/molbev/msy079]
Kimura’s neutral theory argued that positive selection was not responsible for an appreciable fraction of molecular substitutions. Correspondingly, quantitative analysis reveals that the vast majority of substitutions in cancer genomes are not detectably under selection. Insights from the somatic evolution of cancer reveal that beneficial substitutions in cancer constitute a small but important fraction of the molecular variants. The molecular evolution of cancer community will benefit by incorporating the neutral theory of molecular evolution into their understanding and analysis of cancer evolution—and accepting the use of tractable, predictive models, even when there is some evidence that they are not perfect.

Yoder, A.D., Poelstra, J.W., Tiley, G.P., and Williams, R.C. (2018) Neutral Theory Is the Foundation of Conservation Genetics. Molecular Biology and Evolution, 35:1322-1326. [doi: 10.1093/molbev/msy076]
Kimura’s neutral theory of molecular evolution has been essential to virtually every advance in evolutionary genetics, and by extension, is foundational to the field of conservation genetics. Conservation genetics utilizes the key concepts of neutral theory to identify species and populations at risk of losing evolutionary potential by detecting patterns of inbreeding depression and low effective population size. In turn, this information can inform the management of organisms and their habitat providing hope for the long-term preservation of both. We expand upon Avise’s “inventorial” and “functional” categories of conservation genetics by proposing a third category that is linked to the coalescent and that we refer to as “process-driven.” It is here that connections between Kimura’s theory and conservation genetics are strongest. Process-driven conservation genetics can be especially applied to large genomic data sets to identify patterns of historical risk, such as population bottlenecks, and accordingly, yield informed intuitions for future outcomes. By examining inventorial, functional, and process-driven conservation genetics in sequence, we assess the progression from theory, to data collection and analysis, and ultimately, to the production of hypotheses that can inform conservation policies.

Zhang, J. (2018) Neutral Theory and Phenotypic Evolution. Molecular Biology and Evolution, 35:1327-1331. [doi: 10.1093/molbev/msy065]
Although the neutral theory of molecular evolution was proposed to explain DNA and protein sequence evolution, in principle it could also explain phenotypic evolution. Nevertheless, overall, phenotypes should be less likely than genotypes to evolve neutrally. I propose that, when phenotypic traits are stratified according to a hierarchy of biological organization, the fraction of evolutionary changes in phenotype that are adaptive rises with the phenotypic level considered. Consistently, molecular traits are frequently found to evolve neutrally whereas a large, random set of organismal traits were recently reported to vary largely adaptively. Many more studies of unbiased samples of phenotypic traits are needed to test the general validity of this hypothesis.

Rocha, E.P.C. (2018) Neutral Theory, Microbial Practice: Challenges in Bacterial Population Genetics. Molecular Biology and Evolution, 35:1338-1347. [doi: 10.1093/molbev/msy078]
I detail four major open problems in microbial population genetics with direct implications to the study of molecular evolution: the lack of neutral polymorphism, the modeling of promiscuous genetic exchanges, the genetics of ill-defined populations, and the difficulty of untangling selection and demography in the light of these issues. Together with the historical focus on the study of single nucleotide polymorphism and widespread non-random sampling, these problems limit our understanding of the genetic variation in bacterial populations and their adaptive effects. I argue that we need novel theoretical approaches accounting for pervasive selection and strong genetic linkage to better understand microbial evolution.

Arkhipova, I.R. (2018) Neutral Theory, Transposable Elements, and Eukaryotic Genome Evolution. Molecular Biology and Evolution, 35:1332-1337. [doi: 10.1093/molbev/msy083]
Among the multitude of papers published yearly in scientific journals, precious few publications may be worth looking back in half a century to appreciate the significance of the discoveries that would later become common knowledge and get a chance to shape a field or several adjacent fields. Here, Kimura’s fundamental concept of neutral mutation-random drift, which was published 50 years ago, is re-examined in light of its pervasive influence on comparative genomics and, more specifically, on the contribution of transposable elements to eukaryotic genome evolution.

Leitner, T. (2018) The Puzzle of HIV Neutral and Selective Evolution. Molecular Biology and Evolution, 35:1355-1358. [doi: 10.1093/molbev/msy089]
HIV is one of the fastest evolving organisms known. It evolves about 1 million times faster than its host, humans. Because HIV establishes chronic infections, with continuous evolution, its divergence within a single infected human surpasses the divergence of the entire humanoid history. Yet, it is still the same virus, infecting the same cell types and using the same replication machinery year after year. Hence, one would think that most mutations that HIV accumulates are neutral. But the picture is more complicated than that. HIV evolution is also a clear example of strong positive selection, that is, mutants have a survival advantage. How do these facts come together?

Frost, S.D.W., Magalis, B.R., and Kosakovsky Pond, S.L. (2018) Neutral Theory and Rapidly Evolving Viral Pathogens. Molecular Biology and Evolution, 35:1348-1354. [doi: 10.1093/molbev/msy088]
The evolution of viral pathogens is shaped by strong selective forces that are exerted during jumps to new hosts, confrontations with host immune responses and antiviral drugs, and numerous other processes. However, while undeniably strong and frequent, adaptive evolution is largely confined to small parts of information-packed viral genomes, and the majority of observed variation is effectively neutral. The predictions and implications of the neutral theory have proven immensely useful in this context, with applications spanning understanding within-host population structure, tracing the origins and spread of viral pathogens, predicting evolutionary dynamics, and modeling the emergence of drug resistance. We highlight the multiple ways in which the neutral theory has had an impact, which has been accelerated in the age of high-throughput, high-resolution genomics.

Satta, Y., Fujito, N.T., and Takahata, N. (2018) Nonequilibrium Neutral Theory for Hitchhikers. Molecular Biology and Evolution, 35:1362-1365. [doi: 10.1093/molbev/msy093]
Selective sweep is a phenomenon of reduced variation at presumably neutrally evolving sites (hitchhikers) in the genome that is caused by the spread of a selected allele at a linked focal site, and is widely used to test for action of positive selection. Nonetheless, selective sweep may also provide an unprecedented opportunity for studying nonequilibrium properties of the neutral variation itself. We have demonstrated this possibility in relation to ancient selective sweep for modern human-specific changes and ongoing selective sweep for local population-specific changes.

Charlesworth, B., and Charlesworth, D. (2018) Neutral Variation in the Context of Selection. Molecular Biology and Evolution, 35:1359-1361. [doi: 10.1093/molbev/msy062]
In its initial formulation by Motoo Kimura, the neutral theory was concerned solely with the level of variability maintained by random genetic drift of selectively neutral mutations, and the rate of molecular evolution caused by the fixation of such mutations. The original theory considered events at a single genetic locus in isolation from the rest of the genome. It did not take long, however, for theoreticians to wonder whether selection at one or more loci might influence neutral variability at linked sites. Once DNA sequence variability could be studied, and especially when resequencing of whole genomes became possible, it became clear that patterns of neutral variability in genomes are affected by selection at linked sites, and that these patterns could advance our understanding of natural selection, and can be used to detect the action of selection in genomic regions, including selection much weaker than could be detected by direct measurements of the relative fitnesses of different genotypes. We outline the different types of processes that have been studied, in approximate order of their historical development.

Kern, A. D., and Hahn, M. W. (2018) The Neutral Theory in Light of Natural Selection. Molecular Biology and Evolution, 35:1366-1371. [doi: 10.1093/molbev/msy092]
In this perspective, we evaluate the explanatory power of the neutral theory of molecular evolution, 50 years after its introduction by Kimura. We argue that the neutral theory was supported by unreliable theoretical and empirical evidence from the beginning, and that in light of modern, genome-scale data, we can firmly reject its universality. The ubiquity of adaptive variation both within and between species means that a more comprehensive theory of molecular evolution must be sought.

Nekrutenko, A., Team, G., Goecks, J., Taylor, J., and Blankenberg, D. (2018) Biology Needs Evolutionary Software Tools: Let’s Build Them Right. Molecular Biology and Evolution, 35:1372-1375. [doi: 10.1093/molbev/msy084]
Research in population genetics and evolutionary biology has always provided a computational backbone for life sciences as a whole. Today evolutionary and population biology reasoning are essential for interpretation of large complex datasets that are characteristic of all domains of today’s life sciences ranging from cancer biology to microbial ecology. This situation makes algorithms and software tools developed by our community more important than ever before. This means that we, developers of software tool for molecular evolutionary analyses, now have a shared responsibility to make these tools accessible using modern technological developments as well as provide adequate documentation and training.

1. I don't know if this is also true of undergraduates in Asia, Africa, South America, Europe, Australia, and Antarctica.

Kimura, M. (1968) Evolutionary rate at the molecular level. Nature, 217:624-626. [PDF]

King, J.L., and Jukes, T.H. (1969) Non-darwinian evolution. Science, 164:788-798. [PDF]


anonymous said...

Larry Moran said...

Here's the article you linked to.

Theorists Debate How ‘Neutral’ Evolution Really Is
For 50 years, evolutionary theory has emphasized the importance of neutral mutations over adaptive ones in DNA. Real genomic data challenge that assumption.

I read it a few days ago but decided not to comment because there's so much in the article that's misleading. For example, while it's true that hitchhicking effects can result in fixation of nearby alleles, that only happens under fairly strong selection. The linked alleles have to be carried to fixation before recombination unlinks them.

We know from gross comparisons of related species (e.g. humans and chimpanzees) that 90% of the genomes appear to be evolving neutrally at a rate comparable to the rate of mutation. That's because 90% of the genome is junk and mutations in that fraction are neutral.

There's not much point in quibbling about whether all these alleles are fixed by pure random genetic drift or whether some fraction are also affected temporarily by selective sweeps. As Andrew Kern says in the article those sweeps just "add noise to allele frequencies beyond drift."

I note that Kern says he's "agnostic" about how much of the human genome is functional. I think that's revealing.

Robert Byers said...

Is it the averagev scientist, or was meant the average biology scientist, or the average origin/evolutionary biologist? i think what was meant was the last two groups!
Hard to believe these graduates think evolutionism is just natural selection/mutations.
Who is writing the texkbooks/teaching??
They also are not taught the merits of creation(s). Although i saw in a YORK(in toronto) university class on biology a very quick dismissal of ID.
Glad they thought they needed to do it but its weird not to give the students a chance to weigh the matter and not just be asked to memorize how its not true.
We are also in a revolution these days. A creationist revolution led by ID and riding shotgun YEC.

Larry Moran said...

IDiots declared the start of a revolution back in the 1990s.

Nobody came.

People all over the world are abandoning religion. It's happening more slowly in America but it's still happening.

S Johnson said...

Kern and Hahn are key figures in a Quanta piece that demotes neutral theory to controversial.

Donald Forsdyke said...
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dean said...

"A creationist revolution led by ID and riding shotgun YEC."

I agree that creationists and ID backers are trying to destroy science education by pretending their versions of mythology actually has some basis in fact, and is remotely scientific.

But they aren't related to fact, and they have nothing to do with science (no more than ESP does), and so it is a very good thing (if it's true) that students at YORK were told that creationism and ID were nothing short of complete bollocks. That message needs to be stated loudly and clearly.

anonymous said...

I remain somewhat sceptical of “neutral extremism”

OK, accumulation of neutral mutation can, parallel to natural and sexual selection, result in many molecular differences within and between species. So what?

OK, a quick survey of phenotypic differences such as hair or eye colour SEEM to be neutral and SEEM not subject to selection. (I question that presumption)

Adaptionist-extremism (whatever that is supposed to mean) could counter that an an accumulation of neutral variation must pre-exist selection, before environmental change presents novel selection pressures. At this point debate becomes bogged down in semantics.

Not that it matters. Since the Lewinton-Gould paper on “Spandrels”, any last vestige of adaptionist-extremism has gone extinct: rendering moot any rebuttal to what may now be just straw man arguments to no-longer-existent “Panglossian adaptionist fallacy”

Let’s remember that Darwin himself conceded a version of “Neutral Theory” as part and parcel of the evolution narrative. Not even Darwin was a strict “Darwinist”.

"Variations neither useful nor injurious would not be affected by natural selection, and would be left either a fluctuating element, as perhaps we see in certain polymorphic species, or would ultimately become fixed, owing to the nature of the organism and the nature of the conditions." (Darwin, 1859)

Just the same, I question exactly how much of presumed “neutral variability” is in fact “neutral”. Don’t get me wrong; Of course, there is more to evolution than Natural Selection. Of course, the reproductive isolation is more often than not, due to random genetic drift.

That said, your observation that junk DNA from one lineage differs from the junk DNA of a different lineage in accordance with the inexhorable ticking of a molecular clock... strikes me as decidedly underwhelming

Meanwhile, your citation of Kern, and your dismissal of sweeps as “noise”, does not appear to justify an enthusiastic endorsement of Neutral Theory. The advent of genomics has permitted us to test predictions. We still fail to observe a proportional increase of neutral polymorphisms within a species according to the census population size.

I remain convinced Kimura and his successors have overstated their case.

Larry Moran said...

Tages Haruspex said,

That said, your observation that junk DNA from one lineage differs from the junk DNA of a different lineage in accordance with the inexhorable ticking of a molecular clock... strikes me as decidedly underwhelming.

I understand. Adaptationists are only interested in adaptations. They don't care if most of evolution is due to drift because, in their mind, it's not really evolution (until it is, see below).

However, don't forget that the influences of drift and neutral alleles are not limited to junk DNA. The fact that amino acid substitutions in proteins in different lineages give rise to an approximate molecular clock means that most of them are neutral and are fixed by random genetic drift.

Also, I find it very interesting that adaptationists dismiss drift and neutrality until it serves their purpose by providing possible fuel for adaptation. It's called having your cake and eating it too.

Tim Tyler said...

I don't think neutral theory was very much of a revolution. Symbiosis - with the discovery that organisms are menageries and that phylogenetic trees frequently merged as well as dividing - was much bigger. The expansion of the domain of Darwinism to include selection of cultural, psychological and physical variation was also a much bigger revolution. Neutral theory was instead more of a redefinition of terms. Natural selection was redefined so as to include sexual selection and exclude chance phenomena - contrary to Darwin's conception of it which was quite different. Then in the 1960s, chance phenomena were quantified and found to be more common than had been supposed. The supposed neutral revolution arose out of a redefinition of terms.

anonymous said...

I suggest we are arguing at cross purposes

When champions of “Neutral Theory” couch their enthusiasm with caveats along the lines that Selection is real and also important, nobody suggests they are disingenuous. So why should a different standard apply to “adaptionists”? Meanwhile, who exactly is this adaptionist boogeyman whereof you speak? In your original OP, you refer to the “average scientist” and to “80% of Biology undergraduates”. My experience is quite different and can be buttressed by data. Every introductory Biology text I am aware of handily highlights other mechanisms of evolution, other than “Natural Selection”; including founder effects, genetic drift and Sexual Selection. Advanced courses distinguish between Genetic Drift and successive varieties of “Neutral Theory”, which Kimura’s protégées needed to invoke, in order to rescue his initial proposal.

To my understanding: the crux of the problem is as follows:

What is the unit of Selection? If we agree for the moment, the unit of Selection is the individual, then again we are debating at cross purposes when you insist on focusing upon molecular variability. Disregard for the moment the reference to “spandrels” I cited above.

But let’s consider: on what point do we really disagree? Am I correct in assuming that you claim that the majority of traits we observe (at the level of an individual organism) can be and often are fixed in a population by random processes other than by Selection? More to the point: such instances of “Neutral” occurances occur more frequently in populations, than occurrences of “Natural Selection”?

If that is your thesis, I have several objections:

Darwin himself even agreed such could be the case, although I suspect he would have considered some form of Selection to occur with greater frequency than neutral processes. That would be because no observable traits in a population are truly “neutral” if females tend to choose the phenotypes of their fathers (according to some theories, or the contrary according to other theories). This line of discussion will rapidly descend rabbit holes, so moving along:

That all said, my greatest objection defers to Popper’s criterion of falsifiability. The original article I cited claimed that the advent of genomics has at last made Neutral Theory testable. To my understanding, Neutral Theory has so far failed the test. Your dismissal of sweeps merely “adding noise” constitutes simultaneous cake having-eating IMHO. I could be wrong, perhaps I misunderstood you.

S Johnson said...

It is true sexual selection is defined in popularizations as a case of natural selection. But, is there a term for Darwinian success of individuals that leads to lower population overall?

anonymous said...

According to Darwin:

sexual selection “depends not on the struggle for existence, but on the struggle between males for possession of females.” Darwin’s Victorian sensibilities seem to exclude polyandry, but we digress.

Darwin’s pertinent (to this discussion) observation would be how ostensibly MALADAPTIVE traits can be fixed in a population contrary to (and not as an instance of) Natural Selection. Successive commentators have often failed to directly address Darwin’s motivations for parsing his definitions so precisely. Many conflate Sexual Selection as somehow yet another instance of Natural Selection, contrary to Darwin’s was nderstanding.

Robert Byers said...

Well its either a revolution or it is not. I'm sure it is. Or as a creationist sees it CORRECTION from later generations on a hypothesis that is not actually true.
Cultural and psychological selections is not the same thing as whart a correction is talking about and not a revolution.
how can evolutionism be persuasive in a modern culture of doubt if it can't get its history right? For some eh!

Tim Tyler said...

It was a deliberate redefinition away from Darwin's usage. Here's Satoshi Kanazawa (2003) describing what happened:

"In the 1930s, however, biologists redefined natural selection to subsume sexual selection and began to contend that differential reproductive success was the currency of natural selection."

anonymous said...

I was unaware of the historical context, thank you.

In other words, maladaptive is apparent only and becomes adaptive when the trait in question results in the issue of more offspring.

The reason I referred to Darwin’s Sexual Selection was because so-called “randomly generated neutral traits” are no longer “neutral” when mate selection is non-random

If tall dark handsome lotharios have more children than short, pudgy, bald academics (for example); traits previously considered neutral, no longer are.

If females subconsciously choose mates whose phenotypes match their fathers’, Neutral models apply only to cryptic molecular variation.

Possibly (and also likely) females could readily choose “exotic” phenotypes in mate selection

The literature on this subject is fascinating and female monogamy in the Animal World is often as not, not.

Problem here is that focus on animal models really does the vast majority of Biology a disservice.

anonymous said...
This comment has been removed by the author.
John Harshman said...

The question is whether it makes any sense to separate sexual selection out from natural selection. How is it maladaptive? How are members of your own species not part of the environment to which individuals must be adapted?

Rick Prum wrote a whole book arguing the case that sexual selection is different, but I can't see a valid argument there.

Donald Forsdyke said...


Akiyoshi Wada's breathtaking "homostability" theory (1) raised scarcely an eyebrow, while his compatriot's "neutral theory" (2) gained major, mainly mathematically-based, advocates, especially in the USA.

To some of us, Wada's work now appears far more cogent than that of his compatriot. Sadly, Wada's early attempt to get a Japan-based genome project moving, received little support, and the later US-based project gained the high ground.

1. Wada A. et al. (1975) Long range homogeneity of physical stability in double-stranded DNA. Nature 263:439-440.

2. Kimura M (1968) Evolutionary rate at the molecular level. Nature 217:624-626.

S Johnson said...

"The question is whether it makes any sense to separate sexual selection out from natural selection. How is it maladaptive?"

By lowering the population of the species as a whole due to a less useful trait for survival, such as Irish elk antlers or peacock tails, even though they are reproductively advantageous for the individuals. If there is a question, it is whether selection that drives adaptation to a microenvironment should be deemed as adaptive. The fundamental issue is, as it always seems to a layman, of bringing back in omnipotence of natural selection, so that everything is adaptive, even after the initial paragraphs citing neutral and nearly neutral theory, and genetic drift.

"How are members of your own species not part of the environment to which individuals must be adapted?" Try as I may all I can get from this is sexual competition is the defining characteristic of reproductive success and total population of the species is entirely irrelevant. This seems an extreme adaptationist position to me.

Joe Felsenstein said...

OK, I looked up the paper. Interesting -- some sort of local negative correlation of GC versus AT pairs, such that the proportions of them vary less than expected from binomial sampling. They implicate selection in maintaining this. It is observed in the melting curves of DNA in "DNA hybridization" experiments. This was before sequencing was possible. One of the co-authors was Osamu Gotoh, well-known for his work on sequence alignment. One could ask him whether this pattern is seen in DNA sequences. Most of the references to this term seem to come from you in recent years.

By the way, not a competitor of the neutral theory as far as I can see -- it is not in contradiction with neutral or nonneutral phenomena.

John Harshman said...

"Try as I may all I can get from this is sexual competition is the defining characteristic of reproductive success and total population of the species is entirely irrelevant. This seems an extreme adaptationist position to me."

I think you have a distorted view of natural selection. First, what evidence do you have that sexual selection lowers the population of the species as a whole? Second, when you talk about the species as a whole, you're getting into group selection, which is not the same thing as individual selection. You might argue that Darwin blurred the distinction, but I'd say that both he and biologists today generally consider natural selection as operating through individuals through, as you say, individual reproductive success. Also you confuse adaptationism ("everything is selection") with an argument about the meaning of the term "natural selection", when there is no connection between the two.

Tim Tyler said...

I gave sexual selection as an example of how the term "natural selection" had been redefined away from what Darwin intended. However, this thread should be about neutral evolution - sexual selection is interesting, but it is a bit of a digression. At some stage "random" phenomena became excluded from the definition of the term "natural selection". However, the etymology of the term "natural selection" doesn't saying anthing about "random" phenomena - or sampling errors. The distinction was not due to Darwin - it came along later.

John Harshman said...

The etymology of the term "natural selection" doesn't say anything about cotton candy either, but we don't assume that Darwin meant it to incude cotton candy. And I don't think Darwin intended random phenomena to count as natural selection. I certainly don't recall anything in his writings to suggest such a thing.

S Johnson said...

John Harshman, I am correctly reporting to you the meaning conveyed in the overwhelming majority of popularizations of evolution (except Gould and Lewontin.) The default is that natural selection is omnipotent, and everything is adaptive for that reason. Even if there is a paragraph or two about drift and neutral/nearly-neutral theory, those are never considered as alternate hypotheses. Your ostensible issue is with the popularizations.

Group selection is the notion that traits adaptive for the species as a whole can be fixed in a population despite leading to less individual reproductive success. I'm increasingly uncertain how kin selection/inclusive fitness really differs, except for a determination to insist that natural selection is as ever all, and all-powerful.

Lastly, the The notion that larger peacock tails leads to more peacocks in the wild rather than fewer peacocks, though progeny of peacocks with larger tails, seems to me to be what needs a little evidence. Is it speciation is to be regarded as the triumph of adaptation via natural selection? Is low population size, limited habitat or even extinction irrelevant to the success of adaptation via natural selection?

Tim Tyler said...

John Harshman, that seems like a misuse of the null hypothesis, or assuming that the burden of proof lies with others.

I don't know of a passage from Darwin bearing directly on the issue of neutral evolution. However neutral evolution is certainly natural. The issue is whether it counts as "selection". In the dictionary, selection is more or less a synonym choice, and it is certainly possible to choose randomly. One thing Darwin did say is that he would have preferred the phrase "natural preservation" to "natural selection". In that case, the situation would have been even clearer. Preservation can happen at random - that is clear and unambiguous. It is a kind of bizarre adaptationism to only count changes that are non-random. IMO, you are attributing these views to Darwin without a shred of evidence. It goes against the dictionary and against the conventional meanings of these terms. I rate it is a confusing terminological mistake - but I don't think we can blame it on Darwin. His idea of natural selection was quite different from the modern one that excludes genetic drift by definition.

John Harshman said...

S. Johnson: Nobody is claiming that larger peacock tails lead to more peacocks in the wild, necessarily. That, as I mentioned, would be group selection. The definition of natural selection does not include group selection, though one might argue that Darwin made no such distinction if one wanted. Nor is the current definition any sort of power grab by panselectionists. No idea where you're getting all that from.

Tim Tyler: Since Darwin had no notion of genetic drift, I can't imagine how you know he would have included it in his concept of selection. Your proof by etymology is vacuous. It's clear that he didn't consider natural selection to be random but to involve only the spread of advantageous traits.

S Johnson said...

Group selection is where traits advantageous to the group prevail despite a disadvantage to selected individuals. Sexual selection, before it was defined as natural selection (which is to say, adaptive,) was the opposite: Reproductive advantage to individuals was how a maladpative trait for the species would prevail. The prevalence of extinction in the fossil record inclines me to disbelieve natural selection means everything is adaptive, the nearly universal default position despite the mention of genetic drift and neutral/nearly-neutral mutation theory. If larger peacock tails led to more peacocks in the wild, that would indeed be natural selection, and adaptive.

Joe Felsenstein said...

I disagree, to me group selection and sexual selection can occur even when individual selection favors those same traits. As long as they change more owing to their effects on group survival (and group reproduction), or owing to their effects on being chosen as mates, than they would owing to their effects on individual survival and reproduction, then those phenomena can be acting. Think of an allele that is favored by group selection, but is disadvantageous to the individual. You'd call that group selection, so would I. But suppose that the individual's disadvantage is enough that the allele declines in frequency. Is group selection not still acting? You might say it was not there, but I would say that it is still acting, just not enough to prevent loss of the allele. Likewise if sexual selection is acting, favoring an allele, and individual selection on viability also favors it. The one doesn't go away just because the other is present.

Tim Tyler said...

Re: "Since Darwin had no notion of genetic drift, I can't imagine how you know he would have included it in his concept of selection."

He didn't explicitly exclude it. So his definitions and explanations differed from modern ones in that regard. I'm saying that the drift-selection distinction arose due to a redefinition of the term "natural selection" in the 20th century which explicitly excluded neutral evolution in the definition of natural selection. The neutral revolution was the product of a change of terminology.

Re: "It's clear that he didn't consider natural selection to be random but to involve only the spread of advantageous traits."

Er, I'm not arguing that Darwin considered natural selection to be "random". The issue is whether he excluded random influences. He didn't do so explicitly - as far as I know. It is NOT clear that he thought it ONLY involved the spread of advantageous traits. If it was clear there would be some concrete evidence.

John Harshman said...

I suggest reading a book he wrote, On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life. That should give you some idea of what he meant by "natural selection". Trying to pick apart the words in the term is less helpful.

anonymous said...

Darwin anticipated and understood Genetic Drift very well

As already mentioned in at the top of this thread in response to Professor Moran’s unsuccessful attempt to rescue Neutral Theory as a Darwinian Boogeyman.

Let’s remember that not even Darwin was a strict “Darwinist”.

I suggest this particular field of battle is being strewn with slain straw men

"Variations neither useful nor injurious would not be affected by natural selection, and would be left either a fluctuating element, as perhaps we see in certain polymorphic species, or would ultimately become fixed, owing to the nature of the organism and the nature of the conditions." (Darwin, 1859)

anonymous said...
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anonymous said...

Darwin did not understand the molecular underpinnings of inheritance. In fact, his naive beliefs regarding Genetics were expressed in terms which modern texts incorrectly label “Lamarckian”. So what does Neutral Theory offer which manages to contradict the Modern Synthesis? Which falsifiable predictions can be made by Neutral Theory and are unique to Neutral Theory, so much so, that headlines will be able to declare the Modern Theory defunct?

According to Kimura himself, Neutral Theory of Evolution only applies at the molecular level (contrary to the claims of some present) and that phenotypic evolution is primarily controlled by natural selection, as postulated by Charles Darwin and later the Modern Synthesis. What else did Kimura claim?

He proposed that most molecular differences are selectively "neutral" and do not influence the fitness of organisms. The degeneracy of the genetic code or substitution of Amino Acids which do not perturb the tertiary structure of proteins are cases in point. Again, all of this is most underwhelming... ditto psedogenes faster evolution?

Remember Darwin himself insisted that generation of variability was NOT teleological and therefore by definition “neutral’. I also think some present are forgetting the marvellous Delbrück Luria experiment which garnered a Nobel Prize and was touted as a vindication of the Modern Synthesis

So let us restrict our focus to the molecular level.The amount of neutral polymorphisms within a species should increase proportionally with the census population size. Popper would approve: a testable/falsifiable prediction. But alas, such seems not to be the case. So where does this leave us?

anonymous said...

... Modern Synthesis defunct


Joe Felsenstein said...

Once, back in the 1970s, I asked Bryan Clarke, who was one of the leading proponents of panselectionism, whether he would consider himself vindicated if it turned out that 50% of polymorphisms were maintained by selection, the rest being neutral. He said yes.

Soon after, I asked Motoo Kimura the same question. He also said yes.

Joe Felsenstein said...

I said As long as they change more owing to their effects on group survival (and group reproduction), or owing to their effects on being chosen as mates, than they would owing to their effects on individual survival and reproduction, then those phenomena can be acting.

Oops. What I meant to say was that, in the case where these forms of selection are acting in the same direction, as long as they change more than they would with only individual selection, then those phenomena can be acting.

If group, and/or sexual, selection are changing the outcome at all, even when they just speed it up or slow it down, they are acting. It is as in physics, when gravity and electromagnetic forces may be acting in the same direction. Nevertheless we only understand the situation when we understand that they are both acting.

anonymous said...

Great screed in latest online quanta. I am reminded of a great Mark Twain quote: “Reports of my death are greatly exaggerated!”

anonymous said...

I meant to cite Carl Zimmer’s insightful piece

anonymous said...

Joe Felsenstein said...

That issue of Quanta is two years old, so it's not the "latest online quanta".

Joe Felsenstein said...

... and that one's not by Carl Zimmer but by Massimo Pigliucci, who is an advocate and organizer of efforts to declare an Extended Evolutionary Synthesis.

Larry Moran said...

Pigliucci's article is very interesting. I've read most of what he's written in the past and he has always focused on the old-fashioned adaptationist view of the Modern Synthesis. I've never before seem him admit that evolutionary theory underwent a radical change in the late 1960s with the development of Neutral Theory and Nearly-Neutral theory.

Now he says ...

The neutral theory was a landmark conceptual development because for the first time since Darwin it challenged the primacy of natural selection as an agent of evolutionary change. To be sure, Kimura and colleagues didn’t think that phenotypic evolution (i.e., the evolution of complex traits, like eyes, hearts, etc.) occurred in a largely neutral fashion, but if it turned out that much of what goes on at the molecular level is independent of selective processes, then the obvious question is how is it possible that largely neutral molecular variation can give rise to non-neutral phenotypic outcomes. Eventually, the debate about the neutral theory—which raged on intensely for a number of years—was settled with a sensible and empirically consistent compromise: a lot of molecular variation is "near-neutral," which means that the role of stochastic processes such as genetic drift at the molecular level is significantly higher than might have been expected on the basis of a face-value reading of the tenets of the Modern Synthesis.

This raise an obvious question, "Exactly what version of evolutionary theory is he attacking if it's not the Modern Synthesis?"

BTW, I think there are many examples of phenotypic change that are nearly-neutral.

Larry Moran said...

Last year Pigluicci listed a bunch of questions that science is unequipped to answer. One of them was, "In philosophy of science: what role does genetic drift play in the logical structure of evolutionary theory?"

Here's what he says about questions like this:

The scientific literature on all the above is basically non-existent, while the philosophical one is huge. None of the above questions admits of answers arising from systematic observations or experiments. While empirical notions may be relevant to some of them (e.g., the one on abortion), it is philosophical arguments that provide the suitable approach.

Really? See:

One philosopher's view of random genetic drift

anonymous said...

“Nearly ‘Neutral phenotypic change”?

I must be missing something.

Is that not akin to “nearly pregnant”?

At the level of phenotype, even minuscule selection coefficients are nonetheless subject to selection.

What are we talking about again?

anonymous said...

I remain perplexed on one other point:

Darwin himself did not understand the molecular underpinnings of Genetics, however he did understand that there must be some NONTELEOLOGICAL mechanism of generating diversity

This is a fundamental premise of Darwinism-NeoDarwinsim-Modern Synthesis and does not constitute an instance of simultaneous cake-having/eating.

I really would appreciate any intrjections Joe Felsenstein could provide

John Harshman said...

"At the level of phenotype, even minuscule selection coefficients are nonetheless subject to selection."

No. Whether drift or selection predominates depends on the relationship between effective population size and selection coefficient. If I recall, if |s| <= 1/Ne, selection is swamped by drift.

Joe Felsenstein said...
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Joe Felsenstein said...

I have pointed that out to Larry a number of times. It is the basis of Michael Lynch's "drift barrier" argument in his book The Origins of Genome Architecture.

anonymous said...

@John Harshman

Yes of course, forgive my clumsy prose.

I should have included “ ... depending of course EECECTIVE population size.

So how small can a selection coefficient be, to have so little effect (in the face of genetic drift) to have essentially no effect on the probability of the variant in question becoming fixed?

Joe Felsenstein has repeated the math over and over again on this very blog and all to no avail, it would appear.

In a population of effective size N, it must be less than 1/(4N)

Let Joe Felsenstein explain the Math

If I presumptuously pretend to understand Joe Felsenstein, the most innocuous “Neutral” phenotypic trait can have a “minuscule” and even undetectable but significant selection coefficient.

Now that is “minuscule” depending upon effective population size

anonymous said...

@ Joe

My apologies: we just cross-posted

Joe Felsenstein said...

No problem, I do it all the time, there's no easy way to prevent it, and readers should be able to detect it and not be confused by it.

Larry Moran said...

Learning about modern evolutionary theory: the drift-barrier hypothesis

Why doesn't natural selection reduce the mutation rate to zero?