State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute and Center for Evolutionary Biology, Fudan University, Shanghai, China.
Collaborative Innovation Center for Genetics and Development, Fudan University, Shanghai, China.
Mol Biol Evol. 2024 Sep 4;41(9). doi: 10.1093/molbev/msae175.
Modern humans have experienced explosive population growth in the past thousand years. We hypothesized that recent human populations have inhabited environments with relaxation of selective constraints, possibly due to the more abundant food supply after the Last Glacial Maximum. The ratio of nonsynonymous to synonymous mutations (N/S ratio) is a useful and common statistic for measuring selective constraints. In this study, we reconstructed a high-resolution phylogenetic tree using a total of 26,419 East Eurasian mitochondrial DNA genomes, which were further classified into expansion and nonexpansion groups on the basis of the frequencies of their founder lineages. We observed a much higher N/S ratio in the expansion group, especially for nonsynonymous mutations with moderately deleterious effects, indicating a weaker effect of purifying selection in the expanded clades. However, this observation on N/S ratio was unlikely in computer simulations where all individuals were under the same selective constraints. Thus, we argue that the expanded populations were subjected to weaker selective constraints than the nonexpanded populations were. The mildly deleterious mutations were retained during population expansion, which could have a profound impact on present-day disease patterns.
现代人在过去的千年中经历了人口的爆炸式增长。我们假设，由于末次冰期后食物供应更加充足，最近的人类种群生活在选择压力放松的环境中。非同义突变与同义突变的比值（N/S 比值）是衡量选择压力的一种有用且常用的统计方法。在这项研究中，我们使用总共 26419 个东亚线粒体 DNA 基因组重建了一个高分辨率的系统发育树，并根据其祖系的频率将其进一步分为扩张组和非扩张组。我们观察到扩张组中的 N/S 比值要高得多，尤其是对于具有中度有害影响的非同义突变，这表明在扩张的进化枝中，纯化选择的作用较弱。然而，在所有个体都受到相同选择压力的计算机模拟中，这种 N/S 比值的观察结果是不太可能的。因此，我们认为扩张的种群所受到的选择压力比非扩张的种群要小。在种群扩张过程中保留了轻度有害突变，这可能对当今的疾病模式产生深远影响。
