Satta Yoko, Zheng Wanjing, Nishiyama Kumiko V, Iwasaki Risa L, Hayakawa Toshiyuki, Fujito Naoko T, Takahata Naoyuki
School of Advanced Sciences, SOKENDAI (The Graduate University for Advanced Studies).
Graduate School of Systems Life Sciences and Faculty of Arts and Science, Kyushu University.
Genes Genet Syst. 2020 Jan 30;94(6):283-300. doi: 10.1266/ggs.19-00012. Epub 2019 Dec 11.
The two-dimensional site frequency spectrum (2D SFS) was investigated to describe the intra-allelic variability (IAV) maintained within a derived allele (D) group that has undergone an incomplete selective sweep against an ancestral allele group. We observed that recombination certainly muddles the ancestral relationships of allelic lineages between the two allele groups; however, the 2D SFS reveals intriguing signatures of recombination as well as the genealogical structure of the D group, particularly the size of a mutation and the time to the most recent common ancestor (TMRCA). Coalescent simulations were performed to achieve powerful and robust 2D SFS-based statistics with special reference to accurate evaluation of IAV, significance of recombination effects, and distinction between hard and soft selective sweeps. These studies were extended to a case wherein an incomplete selective sweep is no longer in progress and ceased in the recent past. The 2D SFS-based method was applied to 100 intronic linkage disequilibrium regions randomly chosen from the East Asian population of modern humans to examine the P value distributions of the summary statistics under the null hypothesis of neutrality in a nonequilibrium demographic model. We argue that about 96% of intronic variants are non-adaptive with a 10% false discovery rate. Furthermore, this method was applied to six genomic regions in Eurasian populations that were claimed to have experienced recent selective sweeps. We found that two of these genomic regions did not have significant signals of selective sweeps, but the remaining four had undergone hard and soft sweeps and were dated, in terms of TMRCA, after the major out-of-Africa dispersal of modern humans.
研究了二维位点频率谱（2D SFS），以描述在针对祖先等位基因组经历不完全选择性清除的衍生等位基因（D）组中维持的等位基因内变异性（IAV）。我们观察到，重组确实混淆了两个等位基因组之间等位基因谱系的祖先关系；然而，2D SFS揭示了重组的有趣特征以及D组的谱系结构，特别是突变的大小和最近共同祖先的时间（TMRCA）。进行了溯祖模拟，以实现基于2D SFS的强大而稳健的统计，特别参考了IAV的准确评估、重组效应的显著性以及硬选择性清除和软选择性清除之间的区别。这些研究扩展到了一种情况，即不完全选择性清除不再进行且在最近已经停止。基于2D SFS的方法应用于从现代人类东亚人群中随机选择的100个内含子连锁不平衡区域，以检验在非平衡人口模型中性零假设下汇总统计量的P值分布。我们认为，在10%的错误发现率下，约96%的内含子变异是非适应性的。此外，该方法应用于欧亚人群中声称经历了近期选择性清除的六个基因组区域。我们发现，其中两个基因组区域没有显著的选择性清除信号，但其余四个区域经历了硬清除和软清除，并且就TMRCA而言，是在现代人类主要走出非洲扩散之后。
