Department of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Vorbyevy Gory 1-73, Moscow 119992, Russia.
Proc Biol Sci. 2012 Sep 7;279(1742):3409-17. doi: 10.1098/rspb.2012.0776. Epub 2012 Jun 6.
Slow evolution of conservative segments of coding and non-coding DNA is caused by the action of negative selection, which removes new mutations. However, the mode of selection that affects the few substitutions that do occur within such segments remains unclear. Here, we show that the fraction of allele replacements that were driven by positive selection, and the strength of this selection, is the highest within the conservative segments of Drosophila protein-coding genes. The McDonald-Kreitman test, applied to the data on variation in Drosophila melanogaster and in Drosophila simulans, indicates that within the most conservative protein segments, approximately 72 per cent (approx. 80%) of allele replacements were driven by positive selection, as opposed to only approximately 44 per cent (approx. 53%) at rapidly evolving segments. Data on multiple non-synonymous substitutions at a codon lead to the same conclusion and additionally indicate that positive selection driving allele replacements at conservative sites is the strongest, as it accelerates evolution by a factor of approximately 40, as opposed to a factor of approximately 5 at rapidly evolving sites. Thus, random drift plays only a minor role in the evolution of conservative DNA segments, and those relatively rare allele replacements that occur within such segments are mostly driven by substantial positive selection.
保守编码和非编码 DNA 片段的缓慢进化是由负选择作用引起的，负选择会剔除新的突变。然而，影响这些片段内少数替代的选择模式仍不清楚。在这里，我们表明，正选择驱动的等位基因替换的分数，以及这种选择的强度，在果蝇蛋白编码基因的保守片段中最高。麦科德-克里坦测试（McDonald-Kreitman test）应用于黑腹果蝇和拟果蝇的变异数据表明，在最保守的蛋白质片段中，大约 72%（约 80%）的等位基因替换是由正选择驱动的，而在快速进化的片段中，这一比例仅约为 44%（约 53%）。一个密码子上多个非同义替换的数据也得出了相同的结论，并进一步表明，正选择驱动保守位点的等位基因替换最强，因为它通过大约 40 倍的因子加速了进化，而在快速进化的位点则通过大约 5 倍的因子加速了进化。因此，随机漂变在保守 DNA 片段的进化中只起很小的作用，而且这些在保守片段中发生的相对罕见的等位基因替换主要是由实质性的正选择驱动的。
