Assessing the Presence of Recent Adaptation in the Human Genome With Mixture Density Regression.
Assessing the Presence of Recent Adaptation in the Human Genome With Mixture Density Regression.
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DOI：
10.1093/gbe/evad170
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发表时间：
2023-10-06
影响因子：
3.3
通讯作者：
Enard, David
中科院分区：
文献类型：
--
作者：
Salazar-Tortosa, Diego F.;Huang, Yi-Fei;Enard, David
物种之间的基因组差异在多大程度上反映了中性或适应性进化，这是进化基因组学的一个中心问题。事实证明，在人类和其他哺乳动物中，适应性基因组进化与中性基因组进化的存在尤其难以量化。困难主要源于哺乳动物基因组在多个水平上的高度异质性组织(功能序列密度、重组等)。这使得自适应和中性进化信号的解释和区分变得复杂。在这项研究中，我们引入了混合密度回归(MDR)来研究人类基因组中最近适应的决定因素。MDRS提供了一种基于多个高斯分布的灵活回归模型。我们使用MDR来模拟最近的选择信号和可能影响正选择发生/检测的多个基因组因素之间的关联，如果后者首先存在以产生这些关联的话。我们发现，具有两个高斯分布的MDR模型提供了对常见扫描汇总统计量(积分单倍型得分)的全基因组分布的很好的拟合，两个分布中的一个可能在正选择中丰富。我们进一步发现了与最近适应信号相关的几个因素，包括重组率、免疫细胞中调控元件的密度、GC含量、免疫细胞中基因的表达、哺乳动物范围内保守元件的密度以及距离最近的病毒相互作用基因的距离。这些结果支持在最近的人类进化中存在强烈的正选择，并强调MDR是理解最近基因组适应信号的有力工具。
How much genome differences between species reflect neutral or adaptive evolution is a central question in evolutionary genomics. In humans and other mammals, the presence of adaptive versus neutral genomic evolution has proven particularly difficult to quantify. The difficulty notably stems from the highly heterogeneous organization of mammalian genomes at multiple levels (functional sequence density, recombination, etc.) which complicates the interpretation and distinction of adaptive versus neutral evolution signals. In this study, we introduce mixture density regressions (MDRs) for the study of the determinants of recent adaptation in the human genome. MDRs provide a flexible regression model based on multiple Gaussian distributions. We use MDRs to model the association between recent selection signals and multiple genomic factors likely to affect the occurrence/detection of positive selection, if the latter was present in the first place to generate these associations. We find that an MDR model with two Gaussian distributions provides an excellent fit to the genome-wide distribution of a common sweep summary statistic (integrated haplotype score), with one of the two distributions likely enriched in positive selection. We further find several factors associated with signals of recent adaptation, including the recombination rate, the density of regulatory elements in immune cells, GC content, gene expression in immune cells, the density of mammal-wide conserved elements, and the distance to the nearest virus-interacting gene. These results support the presence of strong positive selection in recent human evolution and highlight MDRs as a powerful tool to make sense of signals of recent genomic adaptation.
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DOI：
10.1098/rstb.2019.0575
发表时间：
2020-11-23
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Enard D;Petrov DA
通讯作者：
Petrov DA
影响因子：
10.7
作者：
Hejase HA;Mo Z;Campagna L;Siepel A
通讯作者：
Siepel A
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium
影响因子：
10.7
作者：
Castellano, David;Coronado-Zamora, Marta;Eyre-Walker, Adam
通讯作者：
Eyre-Walker, Adam
影响因子：
7
作者：
Akey, JM;Zhang, G;Shriver, MD
通讯作者：
Shriver, MD