Balanovskaia E V, Nurbaev S D
Institute of Clinical Genetics, Medical Genetics Research Center, Russian Academy of Medical Sciences, Moscow, Russia.
Genetika. 1998 Nov;34(11):1559-73.
A new approach for investigating the selective structure of the gene pool reflecting the type and intensity of selection is proposed. Selection pressure is estimated on the basis of interpopulation gene diversity with the use of the selection intensity index: RS(i) = NeS(i) = 1/4(1/FST(i)-1/Fe). Distributions of RS(i) in gene pools of indigenous populations from all continents and five subregions of the northeastern Eurasia were examined. It was shown that, of all theoretical distributions, only beta-distributions provide a good approximation of RS(i) estimates. Based on the confidence intervals of RS obtained from beta-distributions, genes can be grouped into the three following classes according to their selective structure: LOWER DIFF, NEUTRAL, and SUPER DIFF. These classes, respectively, include genes subjected mainly to stabilizing selection (RS(i) > 0; LOWER DIFF), genes subjected mainly to differentiating selection (RS(i) < 0; SUPER DIFF), and arbitrarily selectively neutral genes (RS(i) approximately 0; NEUTRAL). Simulation of gene pool sampling (10(6) samples from 50 markers for each gene pool) allowed us to characterize the selective structure by determining markers that fall into the same selective class irrespective of the variant for the sampling process. The selective structure of gene pools from six continents (Europe, Asia, Africa, Australia, America, and southeastern Eurasia) and five subregions of northeastern Eurasia was characterized. It was shown that approximately one-third of genes is subjected to selection irrespective of the hierarchical level of the region. In gene pools of Europe, northeastern Eurasia, and European and Ural subregions, the proportion of genes under stabilizing selection was higher, the proportion of selectively neutral genes, lower. Debatable issues of tests for selective neutrality based on heterogeneity of interpopulation gene diversity are considered. These issues include the effect on FST of the hierarchical population structure, sample size, number of subpopulations, and other factors that shift estimates of gene selective values.
提出了一种新方法,用于研究反映选择类型和强度的基因库的选择性结构。基于群体间基因多样性,利用选择强度指数估计选择压力:RS(i)=NeS(i)=1/4(1/FST(i)-1/Fe)。研究了来自各大洲以及欧亚大陆东北部五个次区域的土著群体基因库中RS(i)的分布情况。结果表明,在所有理论分布中,只有贝塔分布能很好地拟合RS(i)估计值。根据从贝塔分布获得的RS置信区间,基因可根据其选择性结构分为以下三类:LOWER DIFF、NEUTRAL和SUPER DIFF。这些类别分别包括主要受稳定选择的基因(RS(i)>0;LOWER DIFF)、主要受分化选择的基因(RS(i)<0;SUPER DIFF)以及任意选择中性的基因(RS(i)≈0;NEUTRAL)。对基因库抽样进行模拟(每个基因库从50个标记中抽取10^6个样本),使我们能够通过确定无论抽样过程的变体如何都属于同一选择类别的标记来表征选择性结构。表征了来自六大洲(欧洲、亚洲、非洲、澳大利亚、美洲和欧亚大陆东南部)以及欧亚大陆东北部五个次区域的基因库的选择性结构。结果表明,无论区域的层次水平如何,约三分之一的基因受到选择。在欧洲、欧亚大陆东北部以及欧洲和乌拉尔次区域的基因库中,受稳定选择的基因比例较高,选择中性基因的比例较低。考虑了基于群体间基因多样性异质性的选择中性检验的争议性问题。这些问题包括群体层次结构、样本大小、亚群体数量以及其他会改变基因选择值估计的因素对FST的影响。