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Genetic Load and Potential Mutational Meltdown in Cancer Cell Populations

文献类型：期刊论文

作者Zhang, Yuezheng2; Li, Yawei2,4; Li, Tao2,4; Shen, Xu2,5; Zhu, Tianqi6,7; Tao, Yong2; Li, Xueying8; Wang, Di2; Ma, Qin2,4; Hu, Zheng2
刊名MOLECULAR BIOLOGY AND EVOLUTION
出版日期2019-03-01
卷号36期号:3页码:541-552
关键词genetic load Muller's ratchet HeLa cell line copy number variation
ISSN号0737-4038
DOI10.1093/molbev/msy231
英文摘要Large genomes with elevated mutation rates are prone to accumulating deleterious mutations more rapidly than natural selection can purge (Muller's ratchet). As a consequence, it may lead to the extinction of small populations. Relative to most unicellular organisms, cancer cells, with large and nonrecombining genome and high mutation rate, could be particularly susceptible to such mutational meltdown. However, the most common type of mutation in organismal evolution, namely, deleterious mutation, has received relatively little attention in the cancer biology literature. Here, by monitoring single-cell clones from HeLa cell lines, we characterize deleterious mutations that retard the rate of cell proliferation. The main mutation events are copy number variations (CNVs), which, estimated from fitness data, happen at a rate of 0.29 event per cell division on average. The mean fitness reduction, estimated reaching 18% per mutation, is very high. HeLa cell populations therefore have very substantial genetic load and, at this level, natural population would likely face mutational meltdown. We suspect that HeLa cell populations may avoid extinction only after the population size becomes large enough. Because CNVs are common in most cell lines and tumor tissues, the observations hint at cancer cells' vulnerability, which could be exploited by therapeutic strategies.
资助项目Strategic Priority Research Program of the Chinese Academy of Sciences[XDB13000000] ; Natural Science Foundation of China[31771416] ; Natural Science Foundation of China[91531305] ; Ministry of Science and Technology, Taiwan[105-2918-I-002-014] ; Ministry of Science and Technology, Taiwan[105-2628-B-002-015-MY3] ; Natural Science Foundation[31771416] ; Natural Science Foundation[31671370] ; Natural Science Foundation[31301093] ; Natural Science Foundation[11201224] ; Natural Science Foundation[11301294] ; Youth Innovation Promotion Association of Chinese Academy of Sciences[2015080] ; Key Research Program of the Chinese Academy of Sciences[KFZD-SW-220]
WOS研究方向Biochemistry & Molecular Biology ; Evolutionary Biology ; Genetics & Heredity
语种英语
WOS记录号WOS:000462585100009
出版者OXFORD UNIV PRESS
源URL[http://ir.amss.ac.cn/handle/2S8OKBNM/34334]  
专题应用数学研究所
通讯作者Wang, Hurng-Yi; Lu, Xuemei
作者单位1.Natl Taiwan Univ, Grad Inst Clin Med, Taipei, Taiwan
2.Beijing Inst Genom, Key Lab Genom & Precis Med, Beijing, Peoples R China
3.Chinese Acad Sci, CAS Ctr Excellence Anim Evolut & Genet, Kunming, Yunnan, Peoples R China
4.Univ Chinese Acad Sci, Beijing, Peoples R China
5.Sun Yat Sen Univ, Sch Life Sci, State Key Lab Biocontrol, Guangzhou, Guangdong, Peoples R China
6.Chinese Acad Sci, Acad Math & Syst Sci, Natl Ctr Math & Interdisciplinary Sci, Beijing, Peoples R China
7.Chinese Acad Sci, Acad Math & Syst Sci, Key Lab Random Complex Struct & Data Sci, Beijing, Peoples R China
8.Peking Univ, Sch Life Sci, Beijing, Peoples R China
9.Natl Taiwan Univ, Inst Ecol & Evolutionary Biol, Taipei, Taiwan
推荐引用方式
GB/T 7714		 Zhang, Yuezheng,Li, Yawei,Li, Tao,et al. Genetic Load and Potential Mutational Meltdown in Cancer Cell Populations[J]. MOLECULAR BIOLOGY AND EVOLUTION,2019,36(3):541-552.
APA Zhang, Yuezheng.,Li, Yawei.,Li, Tao.,Shen, Xu.,Zhu, Tianqi.,...&Lu, Xuemei.(2019).Genetic Load and Potential Mutational Meltdown in Cancer Cell Populations.MOLECULAR BIOLOGY AND EVOLUTION,36(3),541-552.
MLA Zhang, Yuezheng,et al."Genetic Load and Potential Mutational Meltdown in Cancer Cell Populations".MOLECULAR BIOLOGY AND EVOLUTION 36.3(2019):541-552.

入库方式： OAI收割

来源：数学与系统科学研究院

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