Popadin Konstantin, Polishchuk Leonard V, Mamirova Leila, Knorre Dmitry, Gunbin Konstantin
Departments of Genetics, Biological Faculty of M.V. Lomonosov Moscow State University, Vorobyevy Gory 1-12, Moscow 119992, Russia.
Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13390-5. doi: 10.1073/pnas.0701256104. Epub 2007 Aug 6.
After the effective size of a population, N(e), declines, some slightly deleterious amino acid replacements which were initially suppressed by purifying selection become effectively neutral and can reach fixation. Here we investigate this phenomenon for a set of all 13 mitochondrial protein-coding genes from 110 mammalian species. By using body mass as a proxy for N(e), we show that large mammals (i.e., those with low N(e)) as compared with small ones (in our sample these are, on average, 369.5 kg and 275 g, respectively) have a 43% higher rate of accumulation of nonsynonymous nucleotide substitutions relative to synonymous substitutions, and an 8-40% higher rate of accumulation of radical amino acid substitutions relative to conservative substitutions, depending on the type of amino acid classification. These higher rates result in a 6% greater amino acid dissimilarity between modern species and their most recent reconstructed ancestors in large versus small mammals. Because nonsynonymous substitutions are likely to be more harmful than synonymous substitutions, and radical amino acid substitutions are likely to be more harmful than conservative ones, our results suggest that large mammals experience less efficient purifying selection than small mammals. Furthermore, because in the course of mammalian evolution body size tends to increase and, consequently, N(e) tends to decline, evolution of mammals toward large body size may involve accumulation of slightly deleterious mutations in mitochondrial protein-coding genes, which may contribute to decline or extinction of large mammals.
在种群的有效大小N(e)下降后，一些最初因纯化选择而受到抑制的轻度有害氨基酸替换变得实际上是中性的，并能够达到固定状态。在此，我们针对来自110种哺乳动物的所有13个线粒体蛋白质编码基因进行了这一现象的研究。通过使用体重作为N(e)的替代指标，我们发现，与小型哺乳动物（在我们的样本中，它们的平均体重分别为369.5千克和275克）相比，大型哺乳动物（即N(e)较低的那些）相对于同义替换而言，非同义核苷酸替换的积累速率高43%，并且相对于保守替换而言，激进氨基酸替换的积累速率高8%-40%，这取决于氨基酸分类的类型。这些更高的速率导致大型哺乳动物与小型哺乳动物相比，现代物种与其最近重建祖先之间的氨基酸差异大6%。由于非同义替换可能比同义替换更具危害性，并且激进氨基酸替换可能比保守替换更具危害性，我们的结果表明，大型哺乳动物经历的纯化选择效率低于小型哺乳动物。此外，由于在哺乳动物进化过程中体型往往会增大，因此N(e)往往会下降，哺乳动物向大体型的进化可能涉及线粒体蛋白质编码基因中轻度有害突变的积累，这可能导致大型哺乳动物的衰退或灭绝。
