The Neutral Theory of Molecular Evolution in the Genomic Era

Abstract

The neutral theory of molecular evolution has been widely accepted and is the guiding principle for studying evolutionary genomics and the molecular basis of phenotypic evolution. Recent data on genomic evolution are generally consistent with the neutral theory. However, many recently published papers claim the detection of positive Darwinian selection via the use of new statistical methods. Examination of these methods has shown that their theoretical bases are not well established and often result in high rates of false-positive and false-negative results. When the deficiencies of these statistical methods are rectified, the results become largely consistent with the neutral theory. At present, genome-wide analyses of natural selection consist of collections of single-locus analyses. However, because phenotypic evolution is controlled by the interaction of many genes, the study of natural selection ought to take such interactions into account. Experimental studies of evolution will also be crucial.

Evolution of adaptive phenotypic traits without positive Darwinian selection

“…A common feature of these tests is to search for a pattern that might be associated with positive selection under certain circumstances, but also may occur as a result of other factors in the complete absence of positive selection. Thus, they cannot be considered as true tests of the hypothesis of positive selection because they do not decide between positive selection and various alternatives (Nei, 2005;Jensen et al, 2007;Hughes et al, 2008;Hughes, 2007Hughes, , 2008aNei et al, 2010). Moreover, in almost all of the putative cases of positive selection identified by statistical analysis of sequence data alone, the biological basis of the supposed selection and even the phenotypic effects, if any, of the supposedly selected nucleotide substitutions have not been addressed (Hughes, 2007).…”

“…In fact, given the prominence accorded to the Neo-Darwinian mechanism in the biological literature, it may seem surprising that this mechanism has left so few unambiguous traces on the genomes of organisms (Nei et al, 2010;Hernandez et al, 2011). Rather, genomes show evidence that the predominant form of natural selection that occurs in populations is purifying selection; that is, natural selection acting to eliminate deleterious variants (Hughes et al, 2003;Nei et al, 2010).…”

“…Rather, genomes show evidence that the predominant form of natural selection that occurs in populations is purifying selection; that is, natural selection acting to eliminate deleterious variants (Hughes et al, 2003;Nei et al, 2010). The predominance of purifying selection was predicted by Kimura and Ohta (1974), and the fact that their prediction has been proved to be correct is the cornerstone of many routine methods of modern bioinformatics, whereby evolutionary conservation of a sequence element (the consequence of purifying selection) is taken as evidence of that element's functional importance (Lesk, 2008).…”

Cultural evolution of music

“…These changes can be in the direction of simple 76 to complex -and it is possible that there may be a general trend towards complexity 77 (McShea and Brandon 2010; Currie and Mace 2011) -but the reverse is also 78 possible, as are non-directional changes with little or no functional consequences 79 (Nei, Suzuki, and Nozawa 2010). 80…”

Eavesdropping on altered cell-to-cell signaling in cancer by secretome profiling

“…30 Implied by neutral theory, most of the mutations that are retained have a neutral effect on survival or proliferation. 31 Mutations that provide an advantage, endowing the cell with an improved ability to persist and proliferate, are infrequent. Along these lines, Gray and Druker noted that "individual breast cancers typically carry a few consistent and functionally characterized abnormalities, along with tens to thousands of other changes that are rare or unique to the individual tumor and about which little is known."…”