金力郑鸿翔团队：揭示现代人近期扩张过程中负向选择作用的弱化

Mitochondrial DNA Genomes Reveal Relaxed Purifying Selection During Human Population Expansion after the Last Glacial MaximumHong-Xiang Zheng ,1,2,* Shi Yan ,3,4 Menghan Zhang ,5,6 Zhenglong Gu ,1,7Jiucun Wang ,1,2,8 Li Jin 1,2,8,*1State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute and Center for Evolutionary Biology, Fudan University, Shanghai, China2Collaborative Innovation Center for Genetics and Development, Fudan University, Shanghai, China3Ministry of Education Key Laboratory of Contemporary Anthropology, Department of Anthropology and Human Genetics, School of Life Sciences, Fudan University, Shanghai, China4School of Ethnology and Sociology, Minzu University of China, Beijing, China5Institute of Modern Languages and Linguistics, Fudan University, Shanghai, China6Research Institute of Intelligent Complex Systems, Fudan University, Shanghai, China7Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China8Research Unit of Dissecting Population Genetics and Developing New Technologies for Treatment and Prevention of Skin Phenotypes and Dermatological Diseases (2019RU058), Chinese Academy of Medical Sciences, Beijing, China*Corresponding authors: E-mails: zhenghongxiang@fudan.edu.cn; lijin@fudan.edu.cn.Associate editor: Weiwei ZhaiAbstractModern 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 muta-tions (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 mod-erately deleterious effects, indicating a weaker effect of purifying selection in the expanded clades. However, this ob-servation 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.Key words: mitochondrial DNA, relaxation of selective constraints, deleterious mutations, purifying selection.Discoveries Received: November 27, 2023. Revised: July 31, 2024. Accepted: August 06, 2024© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution. This is an Open Access article