Near-neutrality in evolution of genes and gene regulation

“strategies are denoted by i and (N − i). This approach resembles the high temperature limit and seems to be adequate for biological systems where strategy changes have little effect on overall fitness (Ohta, 2002). The elementary steps can increase or decrease the value of i by 1 with probabilities µi+ and µi− given as…”

“Population genetic theory predicts 75 that the strength of purifying selection should increase with effective population size ( N e ).”

“…al. 2003; Haig 2004; Arnqvist & Rowe 2005; Crespi 2007; Presgraves 2007), the stochastic effects of genetic drift (Kimura 1968, 1986; King & Jukes 1969; Ohta 1992, 2002), variable mutation rates (Balloux & LugonMoulin 2002; Hedrick 2005; Noor & Feder 2006), the genomic distribution and effect size…”

“However, the relative percentage of neutral, near-neutra”

“Therefore, the fixation of nearly-neutral alleles of small selective effect is expected to be greatest in small population”

“The relative importance of natural selection vs. genetic drift in explaining evolutionary changes both at molecular (e.g. Kimura, 1983; Mitton, 1994; Ohta, 2002) and phenotypic (e.g. Lande, 1976; Lynch, 1994; Whitlock & Phillips, 2000; O’Hara, 2005) levels constitute a longstanding source of debate…”

“melanogaster and pine trees) offer greater potential for adaptive evolutio”

“Orr (1995) presented a mathematical model of evolution of reproductive isolation.”

“This figure is substantially larger than would be expected if most mutations were neutral or nearly neutra”

“As mentioned, nearly neutral mutations include slightly advantageous as well as slightly deleterious mutations (Ohta, 2002).”

“Rare variants Rare variants were present in only one or two strains, are probably transient, and will tend to disappear during genetic drift [29].”

“Moreover, population size reduction will increase the probability of fixation of deleterious mutations (Ohta, 2002), leading to genomic diversification via the accumulation of molecular changes (Lynch & Conery, 2003) and changes in TE copy numbers (Brookfield & Badge, 1997).”

“The relationship of the neutral theory to selection was explored further with the introduction of the concept of ‘near-neutrality’ [8, 9], in which the extent to which genes are affected by drift and selection is a function of the effective size of a breeding population.”

“Kimura formulated a neutral theory of evolution as early as 1955 [13], which was expanded by Ohta to include nearly neutral conditions [14].”

“Assuming that IS elements proliferate as a result of reduced selection pressure, it follows that this is a neutral process that in itself provides no advantage for the bacterium [43].”

“…variation. tion size not only determines levels of neutral variation, but also affects patterns of nearly neutral variation, al-The analyses of Wright et al. (2003) were based on analyses of variation both within and between popula- though this process is still not well understood (Ohta 2002).”

“2002; Ohta 2002), the important roles of all 13 mtDNA-encoded peptides in cellular energy production suggest that mtDNA variation could have significant metabolic and fitness consequences (William et al .”

“Weak selection is considered as a relevant limit in biology, as most evolutionary changes are driven by small fitness differences [23].”

“In addition to choosing an appropriate species for comparison, the test could be affected by changes in the effective population size [53] and does not consider mutations with small effects on fitness, or slightly deleterious mutations that are selected against in large populations, but behave as neutral in small popu…”

“Among these are Muller’s ratchet,((42,43)) the Hill-Robertson effect,((44,45)) genetic hitchhiking,((46)) population size effect,((47)) and background selection.”

“…6:29:04 PM levels of divergence, small genetic data sets in which variation is largely dominated by neutral or near-neutral processes (Kimura 1983, Ohta 2002) should be expected to be discordant with phenotypic data sets, in which variation is likely dominated by processes that are not…”

“Population size reduction increases the probability of fixation of deleterious mutations [57] and also leads to genome diversification via the accumulation of molecular changes [58].”

“Although a replacement could be selectively neutral, it is unlikely that log s can be routinely below, say, 27 (4).”

“Kimura’s associate, Tomoko Ohta, developed the theoretical understanding of this type of mutation, giving rise to the so-called nearly neutral theory (Ohta 1973, 2002).”

“This is also the assumption made in Ohta’s nearly neutral model of molecular evolution for the fitness effects of new mutant alleles (Ohta and Gillespie 1996, Ohta 2002).”

“Due to low levels of genetic variation and small population size, the evolution of island biotas is hence intuitively expected to be shaped by neutral processes rather than natural selection (Ohta 2002).”

“…sets with high positive values of both Dnondicted by the nearly neutral theory of molecular evolution to be determined by a combination of selection and Dsyn that were not classified among surface proteins of vertebrate parasites were the toxin coregulated pilusand drift (Ohta 1973, 1976, 2002).”

“…and complicated models in light of new evidence and ongoing debate, neither the nearly neutral models articulated by Tomoko Ohta nor the fluctuating selection models articulated by John Gillespie, to cite just two examples, deny a role to either drift or selection (Gillespie 1991; Ohta 2002).”

“While the vast majority of genetic variants are hypothesized to be neutral [1], that is, are assumed not to contribute to any phenotype, the relative percentage of neutral, nearneutral [2] and non-neutral variants remains unclear.”

“Several factors can infl uence the rate of molecular evolution, such as generation time (Bromham et al. 1996, Ohta 2002); metabolic rate (Martin and Palumbi 1993, Gillooly et al. 2005); reproductive mode (Paland and Lynch 2006, Johnson and Howard 2007); or effi ciency of DNA repair machinery (Ota…”

“The nearly neutral model (Ohta 2002) predicts that lineages with small population sizes have higher substitution rates because mutations are more easily fixed due to genetic drift.”

“The reasons given for these deviations from the clock-like model of sequence evolution are related to generation time [124], metabolic rate [125], mutation rate [126], and the effect of effective population size on the rate of fixation of mutations [124].”

“Alternatively, regulatory mutations in most genes may be subject to persistent weak selection (76, 114).”

“Positive selection may be needed to retain the duplicated genes in the population (Ohta 2002; Kondrashov and Kondrashov 2006; Shiu et al. 2006).”

“gif" NDATA ITEM> ]> New alleles become fixed owing to random drift of nearly neutral mutations or to positive selection of substantially advantageous mutation”

“This seems unlikely because for nearly neutral mutations the absolute value jNesj has to be between 1 and 2 (Ohta 2002) and thus the intermediate codon usage bias (as opposed to zero or complete codon usage bias) could vary only within this small window.”

“The finding of negative allometry in the relationship between nonsynonymous and synonymous polymorphisms is thus consistent with the “nearly neutral theory of molecular evolution” (Ohta 2002).”

“Reduced Ne should lead to less efficient selection, so more slightly deleterious amino acid substitutions could go to fixation through drift, rather than being removed from the population by selection (see Ohta and Kimura, 1971; Ohta, 1995, 2002 ).”

“It should be noted that a mutation is considered to be neutral or nearly neutral if its Nes value is ≤ 2 (Ohta, 2002).”

“The outcome has been the emergence of ‘‘nearly neutral’’ theory that explicitly considers the interaction of drift and selection on the genome (Ohta 1992, 2002), perhaps the direction in which the current debate within community ecology will move (Chave 2004).”

“Differences in viral population dynamics, particularly fluctuations in viral effective population size among regions, could create variation in both neutral and non-neutral evolutionary rates (Gillespie, 1999; Ohta, 2002).”

“1Ne 1 (Akashi, 1996; Ohta, 2002), and the further growth of s (past 5.”

“yet poorly conserved sequence evolves by weak negative selection [9].”

“For example, because there are 861 branch pairs in the species tree, on average, 62.5 cases of protein convergence will be obtained in our genome-scale dataset for any particular analysis of two groups of species, although the numbers of analysable branch pairs and hence of detected convergence depend on several facto…”

“Classic neutral theory of evolution has been proposed for the evolution of DNA-binding sites (42, 58), but this process seems too slow to explain their rapid turnover (2, 6, 33, 34, 68).”

“Under the nearly neutral theory [79], where most mutations are only slightly deleterious, genetic drift is stronger in smaller populations (younger population in this case) because larger populations could eliminate even such weaker deleterious mutations.”

“…natural selection is likely to be the most common cause for evolutionary transitions, evolution can also occur by random genetic drift, that is, by gradual random change of gene frequencies as a result of finite population size (see e.g. Whitlock & Phillips 2000; McKay & Latta 2002; Ohta 2002).”

“-regulatory alleles are expected to be present at appreciable frequencies, and an interplay of forces, including changes in effective population size, linkage disequilibrium among selected alleles, and epistatic selection”

“According to the ‘‘nearly neutral theory’’ by Tomoko Ohta (2002), an extended version of ‘‘the neutral mutation-random drift theory’’ proposed by Motoo Kimura (1968), neutral or even ‘‘less harmful’’ genes can become established in a population to some extent if the population size is small enough.”

“If this slightly deleterious mutation becomes fixed during a population bottleneck (Ohta 2002), a subsequent mutation may occur that reintroduces serine at that site but that uses a different codon set from the one used ancestrally.”

“…datasets have gone from purely phenotypic—and thus rich in the signals of natural, sexual, and social selection—to include increasing amounts of genomic information, in which the signal is overwhelmingly neutral or nearly neutral through the effects of mutation and drift (Kimura 1983, Ohta 2002).”

“Because the probabilities of fixation of beneficial and deleterious mutations, respectively, scale positively and negatively with Ne, species with smaller Ne are expected to accumulate more mildly deleterious and fewer beneficial mutations (Ohta 1973, 2002).”

“Given the strong link between effective population size and the efficiency of selection in a certain species, which the nearly neutral theory of molecular evolution suggests [29], it is expected that microorganisms will jettison unnecessary gene clusters very rapidly.”

“Here, we will assume that these PTCs represent both the strongly deleterious mutations that are a result of selection and quickly removed from the populations, as well as the slightly deleterious mutations that are subject to both selection and drift.(36) For example, these X-SNPs may be hot-spot mutations, where the…”

“A great deal of attention has been focused on determining the relative contributions of genetic drift and natural selection to patterns of divergence among genomes (reviewed in Ohta 2002).”

“In this nearly neutral theory, the fate of a mutation depends on the relative forces of selection and drift (Ohta, 2002).”

“Slightly disadvantageous substitutions can drift to high frequencies in small populations (Ohta, 2002), thereby altering substitution rates in the DNA.”

“Population genetic theory predicts that the efficiency of selection should decrease as the effective population size decreses [48].”

“We propose that first, large ancestral northern and southern population sizes could have promoted the accumulation of adaptive mitochondrial variation in each lineage (Fig. 3A; Kimura et al. 1963; Ohta 2002; Camus et al. 2015).”

“Under a population bottleneck, the ‘nearly neutral theory’ predicts that slightly deleterious mutations can drift to high frequencies because purifying selection cannot eliminate them effectively in a small population ( Ohta 1976, 2002 ).”

“…elements, which can provide material for the evolution of novel regulatory mechanisms and complexities in the genome (e.g., Lynch, 2007; Lynch & Conery, 2003; Ohta, 2002; Yi, 2006; Yi & Streelman, 2005, although see Whitney et al., 2011 and Whitney & Garland, 2010 for differing observations).”

“Another mechanistic interpretation for the rate heterogeneity was provided by fixation of nearly neutral, but slightly deleterious, mutations (Ohta 1987, 2002).”

“Being not just another sequence paper, it provides food for thought how positive selection and adaptive evolution may work in species with very large population sizes, which is the domain of the nearly neutral theory of molecular evolution (20, 27).”

“Together, ecological and evolutionary demographic theories suggest a direct connection between stability, competition, lower dispersal, and decreased effective population size (Figure 1).”

“The small population sizes of island species may render selection less effective in the face of stronger genetic drift (Ohta 2002) and the genetic processes that control the rapid morphological and ecological evolution during island adaptive radiations remain unclear.”