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The question is not about the very basics, but more about where the line separating the neutral theory from the rest of population genetics lies.

One often reads/hears claims that "the findings of the neutral theory are still disputed" or that "there's no experimental proof for its validity". It is hard to accept these claims wholesale, since:.

  • It is hardly in doubt that some mutations are neutral
  • It is hardly in doubt that neutral or even slightly deleterious mutations may fix in the population due to genetic drift, or that beneficial mutations may fail to fix for the same reason.

I therefore interpret such statements as attacks on specific points of the neutral theory, or its most sweeping claims (e.g., that most mutations are neutral), or perhaps as attacks on specific meaning of the term. Moreover, such wholesale rejection seems to ignore that the theory may have very different degrees of validity for different organisms (say, more likely to be true for RNA viruses than for mammals).

I will appreciate clarifications of these points.

Update Here is an article that raises several issues regarding the applicability of the neutral theory framework to bacteria: Neutral theory, macrobial practice: challenges in bacterial population genetics

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  • $\begingroup$ I don't often read or hear these claims, but maybe I don't read the correct references. Are these claims being made by population geneticists? Can you provide a few links? $\endgroup$ – Ben Bolker Dec 19 '20 at 20:45
  • $\begingroup$ @BenBolker It recently surfaced quite forcefully in the comments to my answer to another question in this community: biology.stackexchange.com/a/97296/59521 There's a more cautious statement in the Gellespie's little book (that the neutral theory is not generally accepted), and I remember reading in more recent reviews that the debate between the proponents of the neutral theory and the neo-darwinists is not over. $\endgroup$ – Vadim Dec 19 '20 at 21:05
  • $\begingroup$ @BenBolker this is a very good way to think about it! Thanks. $\endgroup$ – Vadim Dec 19 '20 at 21:27
  • $\begingroup$ @BenBolker I think that does deserve to be an answer $\endgroup$ – Maximilian Press Dec 28 '20 at 18:38
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A short answer (converted from a comment): I would call neutral theory a useful null model: in particular, it may be less important that it be a factually correct description of natural systems (i.e. "most alleles can be treated as being neutral (or weakly deleterious") than that it provides a useful standard for distinguishing which alleles are clearly behaving otherwise.

Satta et al (2018) say:

A decade ago, Crow (2008) viewed the then present status of the neutral theory of Kimura (1968) as a standard null model in evolutionary genetics: “Vast regions of the genome are near enough to being neutral for neutrality to be assumed. In fact virtually every study of molecular variability, evolutionary rates, and coalescence is based on this assumption.” At the same time, since he knew Kimura’s devotion to the theory, he felt irony when seeing that reduced neutral variation around a focal site often provided the strongest evidence for selection acting on the site.

In contrast, Gillespie (1994) says (see here):

... we can conclude that both [silent and replacement mutations] are undergoing the same brand of neutral evolution. There cannot be one neutral theory to accept or reject.

The case for neutrality of replacement subsitutions seems particularly weak ... In my view, the neutral theory must be abandoned for replacement substitutions.

Silent substitutions, on the other hand, may well be neutral, although the evidence at the time of this writing is incomplete ... patterns of codon usage and GC% evolution imply that at least some of the silent variation is moderately selected ... we cannot rely on statistical procedures that assume that silent variation is weakly selected and at equilibrium ...


Gillespie, John H. The Causes of Molecular Evolution. Oxford University Press, 1994.

Satta, Yoko, Naoko T Fujito, and Naoyuki Takahata. “Nonequilibrium Neutral Theory for Hitchhikers.” Molecular Biology and Evolution 35, no. 6 (June 1, 2018): 1362–65. https://doi.org/10.1093/molbev/msy093.

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Your question would deserve a long essay. R.C. Lewontin wrote a book ("The genetic basis of evolutionary change" - Columbia U.P) on this subject in 1974, right after the neutral theory had been explicitly formulated in the previous few years. The reasons for the controversy over this theory are still alive some 50 years later, despite the enormous advancements in DNA technology. For example the not so hidden polemical tone of this recent paper would not be understandable if some profound ideological issues were not involved; these issues involve something more than "attacks on specific points of neutral theory, (...) or perhaps as attacks on the specific meaning of the term".

In essence, Lewontin argues that the neutral theory has its philosophical roots in the Platonic notion of "ideal" or "type", for which real objects (the genes, in the present case) are only imperfect approximations. This view, applied to the genetic variation in animal species, implies that the role of natural selection is mainly “purifying”, that is, it acts by removing the slightly deleterious mutations that happens continuously and degrade all genomes (when mutations are perfectly neutral, selection does not act at all). As Kimura and Ohta have said, quoting Muller, “the gene through the long course of evolution has finally found itself in man” (quoted in Lewontin, above, p. 30).

The opposite view (can we refer to it as Democritean?) sees all natural populations, man included, as being continuously modeled by unstable and ever-changing environments, so that any attempt to define an “optimum” is intrinsically meaningless. Genomes are highly integrated pieces of firmware, but they are much more fluid, over the generations, than once thought. This means that all genetic variation may have or may acquire meaning, as their molecular or ecological context changes.

Consider an applied consequence of the two views. One of the claims of most anti-racist geneticists is that the variance component among populations of gene frequencies is much higher than the component within populations; this allegedly falsifies the racist argument according to which the differences observed among human population (races) are mostly genetically determined. But if you claim that most of that genetic variation is irrelevant (“neutral”), what remains are the genes responsible for the differences in phenotypic traits, and it becomes obvious that the variance component among populations in the frequency of these genes is lower with respect to the component within populations; and this may be interpreted as supporting a racist view.

It is not automatic that scientists who prefer one theory to the other also support the philosophical implications of that theory. However, the dispute about the neutral theory of evolution cannot be understood without reference to the above conceptual basis.

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  • $\begingroup$ This is an extremely interesting prospective! This is not what I had in mind when asking the question, but it does give food for thought. Thanks! $\endgroup$ – Vadim Dec 28 '20 at 18:26
  • $\begingroup$ Also, thank you for the references to Lewontin and the Jensen et al. $\endgroup$ – Vadim Dec 28 '20 at 18:28

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