Nicholas School of the Environment, Duke University, Durham, North Carolina, United States of America.
PLoS One. 2011;6(12):e28905. doi: 10.1371/journal.pone.0028905. Epub 2011 Dec 14.
As predicted by the nearly neutral model of evolution, numerous studies have shown that reduced N(e) 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 N(e). Most notably, the genomes of host-dependent bacteria with small N(e) show signatures of genetic drift, including elevated K(a)/K(s). Here, I explore the utility of an alternative measure of selective constraint: the per-site rate of radical and conservative amino acid substitutions (D(r)/D(c)). 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 D(r)/D(c) in endosymbionts that affects the majority (66-79%) of shared orthologs examined. The elevation of D(r)/D(c) in endosymbionts affects all functional categories examined. Simulations indicate that D(r)/D(c) 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 D(r)/D(c) more conservative. Increased D(r)/D(c) 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 D(r)/D(c) across diverse functional categories that include basic cellular processes. Although the current study focuses on a few bacterial lineages, it suggests D(r)/D(c) is a useful gauge of selective constraint and may provide a valuable alternative to K(a)/K(s) when high sequence divergences preclude estimates of K(s). Broader application of D(r)/D(c) will benefit from approaches less prone to estimation biases.
正如进化的近中性模型所预测的那样，许多研究表明，N(e) 的减少会加速遗传漂变下轻微有害变化的积累。虽然这些研究主要集中在真核生物上，但细菌也提供了极好的模型来探索 N(e) 的影响。最值得注意的是，N(e) 较小的宿主依赖细菌的基因组显示出遗传漂变的特征，包括升高的 K(a)/K(s)。在这里，我探讨了另一种选择压力衡量标准的效用：激进和保守氨基酸替换的每个位点速率(D(r)/D(c))。我测试了以下假设：与相关的γ变形菌相比，两种昆虫内共生体（蚂蚁的 Blochmannia 和蚜虫的 Buchnera）中，针对激进氨基酸变化的净化选择效果较差。基因组比较表明，内共生体中 D(r)/D(c) 的显著升高影响了所检查的大多数（66-79%）共有直系同源物。D(r)/D(c) 的升高影响了所有检查的功能类别。模拟表明，D(r)/D(c) 的估计值对密码子频率和突变参数敏感；然而，估计偏差的方向与基因组比较中观察到的模式相反，从而使对升高的 D(r)/D(c) 的推断更加保守。内共生体中 D(r)/D(c) 的增加和其他基因组退化的特征与它们小种群中遗传漂变的强烈影响以及这些无性细菌中与选择位点的连锁一致。虽然对激进替换的松弛选择可能会有所贡献，但基因组范围的过程，如遗传漂变和连锁，最能解释 D(r)/D(c) 在包括基本细胞过程在内的各种功能类别中的普遍升高。虽然当前的研究集中在少数细菌谱系上，但它表明 D(r)/D(c) 是选择压力的有用指标，并且当高序列分歧排除对 K(s) 的估计时，它可能是 K(a)/K(s) 的有价值替代。D(r)/D(c) 的更广泛应用将受益于不易受到估计偏差影响的方法。
