Abstract
As predicted by the nearly neutral model of evolution, numerous studies have shown that reduced Ne accelerates the accumulation of slightly deleterious changes under genetic drift. While such studies have mostly focused on eukaryotes, bacteria also offer excellent models to explore the effects of Ne. Most notably, the genomes of host-dependent bacteria with small Ne show signatures of genetic drift, including elevated Ka/Ks. Here, I explore the utility of an alternative measure of selective constraint: the per-site rate of radical and conservative amino acid substitutions (Dr/Dc). I test the hypothesis that purifying selection against radical amino acid changes is less effective in two insect endosymbiont groups (Blochmannia of ants and Buchnera of aphids), compared to related gamma-Proteobacteria. Genome comparisons demonstrate a significant elevation in Dr/Dc in endosymbionts that affects the majority (66–79%) of shared orthologs examined. The elevation of Dr/Dc in endosymbionts affects all functional categories examined. Simulations indicate that Dr/Dc estimates are sensitive to codon frequencies and mutational parameters; however, estimation biases occur in the opposite direction as the patterns observed in genome comparisons, thereby making the inference of elevated Dr/Dc more conservative. Increased Dr/Dc and other signatures of genome degradation in endosymbionts are consistent with strong effects of genetic drift in their small populations, as well as linkage to selected sites in these asexual bacteria. While relaxed selection against radical substitutions may contribute, genome-wide processes such as genetic drift and linkage best explain the pervasive elevation in Dr/Dc across diverse functional categories that include basic cellular processes. Although the current study focuses on a few bacterial lineages, it suggests Dr/Dc is a useful gauge of selective constraint and may provide a valuable alternative to Ka/Ks when high sequence divergences preclude estimates of Ks. Broader application of Dr/Dc will benefit from approaches less prone to estimation biases.
Highlights
Evolutionary significance of Ne In considering the evolutionary fate of a new mutation, a critical parameter is the product of the selection coefficient (s) for or against that mutation and effective population size (Ne), which dictates the efficacy of selection
I focused on a few bacterial lineages, this study offers proof in concept that Dr/Dc is useful for assessing selective constraint and may offer a valuable tool when high sequence divergences preclude reliable estimates of Ks
I explored the utility of Dr/Dc, an alternative index for selective constraint that is based on physiochemical effects of amino acid changes
Summary
Evolutionary significance of Ne In considering the evolutionary fate of a new mutation, a critical parameter is the product of the selection coefficient (s) for or against that mutation and effective population size (Ne), which dictates the efficacy of selection. Selection determines the fate of mutations that are strongly deleterious or advantageous (|Nes|&10), and mutations with negligible fitness effects (|Nes|%1) should behave neutrally. Ohta [1,2] emphasized that many mutations fall into this ‘nearly neutral’ category, with selection coefficients near the reciprocal of Ne. In general, a random mutation is more likely to be deleterious than beneficial [3,4]. Ohta proposed that the fate of mildly deleterious mutations depends on Ne. Namely, when Ne is reduced, genetic drift plays a greater role and purifying selection against such mutations is less effective. When Ne is reduced, genetic drift plays a greater role and purifying selection against such mutations is less effective This theory generated a key prediction: reduced Ne will lead to the greater accumulation of deleterious changes
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