Neutral Theory of Molecular Evolution - Overview

Overview

While some scientists, such as Sueoka (1962), had hinted that perhaps neutral mutations were widespread, a coherent theory of neutral evolution was first formalized by Motoo Kimura in 1968, followed by a 1969 article by Jack L. King and Thomas H. Jukes, "Non-Darwinian Evolution".

Kimura posited that when one compares the genomes of existing species, the vast majority of molecular differences are selectively "neutral", i.e. the molecular changes represented by these differences do not influence the fitness of the individual organism. As a result, the theory regards these genomic features as neither subject to, nor explicable by, natural selection. This view is based in part on the degenerate genetic code, in which sequences of three nucleotides (codons) may differ and yet encode the same amino acid (GCC and GCA both encode alanine, for example). Consequently, many potential single-nucleotide changes are in effect "silent" or "unexpressed" (see synonymous or silent substitution). Such changes are presumed to have little or no biological effect. However, it should be noted that the original theory was based on the consistency in rates of amino acid changes, and hypothesized that the majority of those changes were also neutral.

A second hypothesis of the neutral theory is that most evolutionary change is the result of genetic drift acting on neutral alleles. A new allele arises typically through the spontaneous mutation of a single nucleotide within the sequence of a gene. In single-celled organisms, such an event immediately contributes a new allele to the population, and this allele is subject to drift. In sexually reproducing multicellular organisms, the nucleotide substitution must arise within one of the many sex cells that an individual carries. Then only if that sex cell participates in the genesis of an embryo does the mutation contribute a new allele to the population. Neutral substitutions create new neutral alleles.

Through drift, these new alleles may become more common within the population. They may subsequently be lost, or in rare cases they may become fixed, meaning that the new allele becomes standard in the population.

According to the mathematics of drift, when comparing divergent populations, most of the single-nucleotide differences can be assumed to have accumulated at the same rate as individuals with mutations are born. This latter rate, it has been argued, is predictable from the error rate of the enzymes that carry out DNA replication; these enzymes have been well studied and are highly conserved across all species. Thus the neutral theory provides a rationale for the molecular clock, although the discovery of a molecular clock predates neutral theory. The observed overdispersion of the molecular clock is not predicted by or compatible with neutral theory.

Many molecular biologists and population geneticists also contributed to the development of the neutral theory, which may be viewed as an offshoot of the modern evolutionary synthesis.

Neutral theory does not contradict natural selection, nor does it deny that selection occurs. Hughes writes: "Evolutionary biologists typically distinguish two main types of natural selection: purifying selection, which acts to eliminate deleterious mutations; and positive (Darwinian) selection, which favors advantageous mutations. Positive selection can, in turn, be further subdivided into directional selection, which tends toward fixation of an advantageous allele, and balancing selection, which maintains a polymorphism. The neutral theory of molecular evolution predicts that purifying selection is ubiquitous, but that both forms of positive selection are rare, whereas not denying the importance of positive selection in the origin of adaptations." In another essay, Hughes writes: "Purifying selection is the norm in the evolution of protein coding genes. Positive selection is a relative rarity — but of great interest, precisely because it represents a departure from the norm."