Effective population size and the rate and pattern of nucleotide substitutions

Abstract

Both the overall rate of nucleotide substitution and the relative proportions of synonymous and non-synonymous substitutions are predicted to vary between species that differ in effective population size (N(e)). Our understanding of the genetic processes underlying these lineage-specific differences in molecular evolution is still developing. Empirical analyses indicate that variation in substitution rates and patterns caused by differences in N(e) is often substantial, however, and must be accounted for in analyses of molecular evolution.

Figure 1

The distributions of fitness effects modelled by Ohta (1977) (exponential or gamma with β=1, dashed curve) and Kimura (1979) (gamma with β=0.5, solid curve). In a small population, with effective population size N_eS, mutations with selection coefficients between 1/N_eS and zero will be effectively neutral. Fewer mutations, those with selection coefficients between 1/N_eL and zero, will be effectively neutral in a larger population with N_eL. The proportion of mutations that have selective coefficients between 1/N_eS and 1/N_eL will be greater under a gamma distribution of fitness effects with β=1 than with β=0.5 for most regions of parameter space.

Figure 2

Example distributions of fitness effects estimated from different datasets, including lognormal for Drosophila miranda and Drosophila pseudoobscura (Loewe & Charlesworth 2006; dotted curve), strongly leptokurtic gamma for Drosophila melanogaster (solid curve) and human (spaced dashed curve) nuclear genes (Keightley & Eyre-Walker 2007), and normal for primate mitochondrial genes (Nielsen & Yang 2003; closed dashed curve).