Genetic Load and Potential Mutational Meltdown in Cancer Cell Populations

doi:10.1093/molbev/msy231

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	Genetic Load and Potential Mutational Meltdown in Cancer Cell Populations
	Zhang, Yuezheng 1; Li, Yawei 1,3; Li, Tao 1,3; Shen, Xu 1,4; Zhu, Tianqi5,6 ; Tao, Yong 1; Li, Xueying 7; Wang, Di 1; Ma, Qin 1,3; Hu, Zheng 1; Liu, Jialin 1; Ruan, Jue 1; Cai, Jun 1,3; Wang, Hurng-Yi 8,9; Lu, Xuemei 1,2,3
	2019-03-01
发表期刊	MOLECULAR BIOLOGY AND EVOLUTION
ISSN	0737-4038
卷号	36 期号:3 页码:541-552
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.
关键词	genetic load Muller's ratchet HeLa cell line copy number variation
DOI	10.1093/molbev/msy231
语种	英语
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
WOS类目	Biochemistry & Molecular Biology ; Evolutionary Biology ; Genetics & Heredity
WOS记录号	WOS:000462585100009
出版者	OXFORD UNIV PRESS
引用统计
文献类型	期刊论文
条目标识符	http://ir.amss.ac.cn/handle/2S8OKBNM/34335
专题	应用数学研究所
通讯作者	Wang, Hurng-Yi; Lu, Xuemei
作者单位	1.Beijing Inst Genom, Key Lab Genom & Precis Med, Beijing, Peoples R China 2.Chinese Acad Sci, CAS Ctr Excellence Anim Evolut & Genet, Kunming, Yunnan, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China 4.Sun Yat Sen Univ, Sch Life Sci, State Key Lab Biocontrol, Guangzhou, Guangdong, Peoples R China 5.Chinese Acad Sci, Acad Math & Syst Sci, Natl Ctr Math & Interdisciplinary Sci, Beijing, Peoples R China 6.Chinese Acad Sci, Acad Math & Syst Sci, Key Lab Random Complex Struct & Data Sci, Beijing, Peoples R China 7.Peking Univ, Sch Life Sci, Beijing, Peoples R China 8.Natl Taiwan Univ, Grad Inst Clin Med, Taipei, Taiwan 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.