KMS Of Academy of mathematics and systems sciences, CAS
| Genetic Load and Potential Mutational Meltdown in Cancer Cell Populations | |
Zhang, Yuezheng1; Li, Yawei1,3; Li, Tao1,3; Shen, Xu1,4; Zhu, Tianqi5,6 ; Tao, Yong1; Li, Xueying7; Wang, Di1; Ma, Qin1,3; Hu, Zheng1; Liu, Jialin1; Ruan, Jue1; Cai, Jun1,3; Wang, Hurng-Yi8,9; Lu, Xuemei1,2,3
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| 2019-03-01 | |
| Source Publication | MOLECULAR BIOLOGY AND EVOLUTION
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| ISSN | 0737-4038 |
| Volume | 36Issue:3Pages:541-552 |
| Abstract | 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. |
| Keyword | genetic load Muller's ratchet HeLa cell line copy number variation |
| DOI | 10.1093/molbev/msy231 |
| Language | 英语 |
| Funding Project | 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 Research Area | Biochemistry & Molecular Biology ; Evolutionary Biology ; Genetics & Heredity |
| WOS Subject | Biochemistry & Molecular Biology ; Evolutionary Biology ; Genetics & Heredity |
| WOS ID | WOS:000462585100009 |
| Publisher | OXFORD UNIV PRESS |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.amss.ac.cn/handle/2S8OKBNM/34335 |
| Collection | 应用数学研究所 |
| Corresponding Author | Wang, Hurng-Yi; Lu, Xuemei |
| Affiliation | 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 |
| Recommended Citation 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. |
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