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a review by Gert Korthof
1 Jan 1999 (updated 3 Nov 2016)
"Looking back, I think that it is a curious human nature, that if a certain doctrine is constantly being spoken of favorably by the majority, endorsed by top authorities in their books and taught in classes, then a belief is gradually built up in one's mind, eventually becoming the guiding principle and the basis of value judgement. At any rate, this was the time when the panselectionist or 'neo-Darwinian' position was most secure in the history of biology: the heyday of the traditional 'synthetic theory' of evolution."|
I included Kimura on this website to show that a critique of Darwinism is possible, without being ridiculed or ignored by the scientific community. Kimura's 'Neutral Theory' got a firm place in the standard textbooks (2) on evolution and population genetics, despite being clearly anti-selectionist. In the beginning orthodox Darwinists did not exactly like Kimura's theory, because he was telling the scientific community that all-powerful Natural Selection was not so powerful after all. Natural selection had its limitations. On the molecular level the power of Natural Selection was greatly minimised, if not banished at all.
Randomness took its place. Molecular variation in proteins and DNA was uncovered that had no influence on the fitness of the individual organism: in other words: is selectively neutral. One could even doubt if Natural Selection was of any importance in the traditional areas of morphology and anatomy.
Why then did Kimura find its place in evolution textbooks, unlike other anti-Darwinists?
What are neutral mutations?Neutral (or silent or synonymous) mutations occur when the change of a single DNA nucleotide (A,T,C,G) within a gene does not affect the sequence of amino acids that make up the gene's protein (15). The sequence of amino acids determines the 3-D structure of the protein, and that determines the function of the protein in the cell, and that determines the fitness of the organism. So, if the protein is not changed it will have no effect on the phenotype and the fitness of the organism. In other words: it will be neutral.
Remarkably, it has been forgotten by most Darwinists, that Charles Darwin distinguished three kinds of variations: advantageous, deleterious, and neutral (13). He wrote at the beginning of chapter 'Natural Selection' of his The Origin of Species: "Variations neither useful nor injurious would not be affected by natural selection, and would be left a fluctuating element" (14). However, Darwin did not elaborate on this idea, and it has not become part of the Modern Synthesis (19).
Were neo-Darwinists really opposed to 'neutralism' in the 70's and 80's?The (nearly) neutral theory is a major departure from the Modern Synthesis selectionist paradigm as it explicitly posits that the majority of mutations fixed during evolution are not affected by Darwinian (positive) selection (18). By the 1980s many evolutionary geneticists had accepted the neutral theory (19). An important exception was Ernst Mayr. Consider Ernst Mayr's Populations, Species, and Evolution (1971) (3). After summarising the evidence for genetic drift (King and Jukes (1969), Kimura(1969), Fitch and Margoliash (1970)), Mayr notes that a number of considerations largely deprive the evidence of its cogency:
My own feeling is that selection is far more important than admitted by the promoters of non-Darwinian evolution, but that indeed there is a random component in much of the variation at some gene loci." (4)So according to Mayr (1982) selection is still more important than neutral mutations or 'Random-Walk Evolution' as he calls it.
Stephen Jay Gould (5) told an interesting anecdote about Ernst Mayr at a meeting of the Evolution Society. Ernst Mayr attacked the claim that single base mutations in DNA that do not result in a different amino acid are not detected by natural selection (neutral mutations or silent mutations). Mayr claimed that such changes could not a priori and in principle be neutral. These mutations must have some effect on the organism, perhaps energetic, that selection can "see" even if the coded amino acid does not change (12). According to Gould this is a clear example of dogmatism. However, there is now a growing body of evidence that 'silent' point mutations do have effect for example on the rate of translation at ribosomes (17), (21). The cause is that multiple codons can code for the same amino acid. Those equivalent codons do not have equal frequncies in the DNA of an organism. There are frequent and rare codons. The frequent silent mutations apparently speed up and the rare silent mutations slow down protein synthesis. Therefore, they have an effect on fitness. So, Mayr was right afterall, but wrong in basing his claims on a priori principles instead of on empirical data.
In his One Long Argument (1991) Mayr tells us about the neutral theory of evolution that
"Although, this theory was at first vigorously opposed by most evolutionists, including myself, the high frequency of "neutral" base-pair replacements is now well established. On the other hand, the selective significance of numerous alleles that had been considered neutral by neutrality enthousiasts has also been established (for instance by Nevo,1983)." (8).According to Mark Ridley, Ernst Mayr still rejects the neutral theory in his What Evolution is (2002).
"I'd rate Motoo Kimura's neutral theory as among the biggest, if not the biggest, contribution to evolutionary biology in the past 35 years. Mayr dismisses it in a short paragraph, as if it were an elementary conceptual mistake. He does not make his objection completely clear. However, he objects to the definition of evolution as changes in gene frequency. Neutrality is a property of genes, and neutral drift produces changes in gene frequency. For Mayr, neutral evolution is impossible because the sorts of change produced by neutral drift are not real evolution." (6)At his 100th birthday Mayr summarises the importance of neutralism by omitting it in an overview of 80 years of evolutionary biology:
"It would seem justified to assert that, so far, no revision of the Darwinian paradigm has become necessary as a consequence of the spectacular discoveries of molecular biology". (10).Please note that 'the neutral theory of evolution' is not sufficient to explain complex life and adaptations. In that sense it is not a theory of evolution. However it is accepted that the neutral theory explains a lot of differences in DNA. Kimura:
"Of course, Darwinian change is necessary to explain change at the phenotypic level -fish becoming man- but in terms of molecules, the vast majority of them are not like that." (7)This is an important admission. If evolution is defined at the morfological level, the evolution of adaptations such as eyes and brains, then natural selection is very important.
The nearly neutral theory
Later it became clear that the exact form of molecular evolution does not neatly fit the original neutral theory, "purely neutral", in several respects. The modified theory, "the nearly neutral theory", posits a class of nearly neutral mutations and can account for several observations that presented problems for Kimura's purely neutral theory (9).
Weak neutralismRecently, population geneticist Kondrashov described Kimura's theory as weak neutralism. He says that "in 1968 Kimura made his modest proposal that most allele substitutions and polymorphisms do not substantially affect an organism's fitness and are governed, not by positive or balancing selection, but by random drift. Kimura still allowed for negative selection to eliminate most new mutations, so his proposal can be regarded as 'weak neutralism'." (11). Kondrashov also points out that the relative power of selection and neutralism depends on which parts of a genome are considered: non-protein-coding versus protein-coding sites and which organisms: insects (fruitfly) or mammals (humans). In mammals negative selection is weak or inefficient resulting in much junk DNA, while in fruitflies efficient selection eliminates much junk DNA. Presumably this is because large animals have small populations and reproduce slowly, while small animals have large populations and reproduce quickly.
The Current Status of the Neutral TheoryThe Neutral Theory of molecular evolution explains the clocklike evolution of DNA. It also explains that silent substitutions outnumber replacement substitutions in most genes. So, the Neutral Theory is extraordinary useful. However, from studies in fruit flies it appears that the main claim of the Neutral Theory, that the vast majority of nucleotide changes that become fixed in populations are selectively neutral, is wrong (16). Also a growing body of evidence shows that 'silent' (synonymous) mutations do have effects on fitness (15), so are not silent at all. It seems, afterall, Mayr was -at least partially- right.
Neutral (or silent or synonymous) mutations are mutations that do not change the amino acid in the protein. A good example of sequences that accumulate neutral mutations are introns. Introns are spliced out from the gene before they can get translated to proteins. So, there can be no selection pressure on intronic sequences. However, in the early 2000's scientists discovered that some "silent" mutations do effect proteins. Synonymous mutations in the end of exons (the protein coding part of a gene) close to the exon-intron border destroy the definition of the border. As a consequence the splicing machinery does not recognize the end of the exon and does not remove the intron. A longer protein will be produced with unknown properties or more likely a nonfunctional or harmful protein. In other words: a synonymous mutation that is not neutral (20).
|Copyright © 1999/2001 G.Korthof||First published: 01-01-1999||Last update: 3 Nov 2016 Notes/FR: 3 Nov 2016|