CSpace  > 应用数学研究所
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
2019-03-01
Source PublicationMOLECULAR BIOLOGY AND EVOLUTION
ISSN0737-4038
Volume36Issue:3Pages:541-552
AbstractLarge 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.
Keywordgenetic load Muller's ratchet HeLa cell line copy number variation
DOI10.1093/molbev/msy231
Language英语
Funding ProjectStrategic 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 AreaBiochemistry & Molecular Biology ; Evolutionary Biology ; Genetics & Heredity
WOS SubjectBiochemistry & Molecular Biology ; Evolutionary Biology ; Genetics & Heredity
WOS IDWOS:000462585100009
PublisherOXFORD UNIV PRESS
Citation statistics
Document Type期刊论文
Identifierhttp://ir.amss.ac.cn/handle/2S8OKBNM/34335
Collection应用数学研究所
Corresponding AuthorWang, Hurng-Yi; Lu, Xuemei
Affiliation1.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.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Zhang, Yuezheng]'s Articles
[Li, Yawei]'s Articles
[Li, Tao]'s Articles
Baidu academic
Similar articles in Baidu academic
[Zhang, Yuezheng]'s Articles
[Li, Yawei]'s Articles
[Li, Tao]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Zhang, Yuezheng]'s Articles
[Li, Yawei]'s Articles
[Li, Tao]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.