Neutral theory of molecular evolution

The neutral theory allows for the possibility that most mutations are deleterious, but holds that because these are rapidly removed by natural selection, they do not make significant contributions to variation within and between species at the molecular level.

Because only a fraction of gametes are sampled in each generation of a species, the neutral theory suggests that a mutant allele can arise within a population and reach fixation by chance, rather than by selective advantage.

[1] The theory was introduced by the Japanese biologist Motoo Kimura in 1968, and independently by two American biologists Jack Lester King and Thomas Hughes Jukes in 1969, and described in detail by Kimura in his 1983 monograph The Neutral Theory of Molecular Evolution.

The proposal of the neutral theory was followed by an extensive "neutralist–selectionist" controversy over the interpretation of patterns of molecular divergence and gene polymorphism, peaking in the 1970s and 1980s.

Neutral theory is frequently used as the null hypothesis, as opposed to adaptive explanations, for describing the emergence of morphological or genetic features in organisms and populations.

[7] Fisher, however, gave a reasoned argument for believing that, in practice, neutral gene substitutions would be very rare.

[8] A coherent theory of neutral evolution was first proposed by Motoo Kimura in 1968[9] and by King and Jukes independently in 1969.

Haldane, R.A. Fisher, and Sewall Wright, created a mathematical approach to analyzing gene frequencies that contributed to the development of Kimura's theory.

Kimura and Ohta also estimated that the alpha and beta chains on the surface of a hemoglobin protein evolve at a rate almost ten times faster than the inside pockets, which would imply that the overall molecular structure of hemoglobin is less significant than the inside where the iron-containing heme groups reside.

[15] Kimura also developed the infinite sites model (ISM) to provide insight into evolutionary rates of mutant alleles.

According to the neutral theory of molecular evolution, the amount of genetic variation within a species should be proportional to the effective population size.

A heated debate arose when Kimura's theory was published, largely revolving around the relative percentages of polymorphic and fixed alleles that are "neutral" versus "non-neutral".

A genetic polymorphism means that different forms of particular genes, and hence of the proteins that they produce, are co-existing within a species.

Selectionists claimed that such polymorphisms are maintained by balancing selection, while neutralists view the variation of a protein as a transient phase of molecular evolution.

Selectionists, on the other hand, contribute environmental conditions to be the major determinants of polymorphisms rather than structural and functional factors.

[16] According to the neutral theory of molecular evolution, the amount of genetic variation within a species should be proportional to the effective population size.

Levels of genetic diversity vary much less than census population sizes, giving rise to the "paradox of variation" .

Therefore, the emergence of the A:B interaction "presuppresses" the deleterious nature of the mutation, making it a neutral change in the genome that is capable of spreading through the population via random genetic drift.

[35] In this case, the loss of B or the A:B interaction would have a negative effect on fitness and so purifying selection would eliminate individuals where this occurs.

[36] CNE, which does not invoke adaptationist mechanisms for the origins of more complex systems (which involve more parts and interactions contributing to the whole), has seen application in the understanding of the evolutionary origins of the spliceosomal eukaryotic complex, RNA editing, additional ribosomal proteins beyond the core, the emergence of long-noncoding RNA from junk DNA, and so forth.

[37][38][39][40] In some cases, ancestral sequence reconstruction techniques have afforded the ability for experimental demonstration of some proposed examples of CNE, as in heterooligomeric ring protein complexes in some fungal lineages.

Grounds for invoking CNE as a null include that it does not presume that changes offered an adaptive benefit to the host or that they were directionally selected for, while maintaining the importance of more rigorous demonstrations of adaptation when invoked so as to avoid the excessive flaws of adaptationism criticized by Gould and Lewontin.

[31] In addition, nucleotide and amino acid substitutions generally accumulate over time in a linear fashion, which is consistent with neutral theory.

[47] Empirical support for the neutral theory may vary depending on the type of genomic data studied and the statistical tools used to detect positive selection.