气候变化领域集成服务门户(CCPortal): A rapidly reversible mutation generates subclonal genetic diversity and unstable drug resistance

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DOI	10.1073/pnas.2019060118
	A rapidly reversible mutation generates subclonal genetic diversity and unstable drug resistance
	Dan L.; Li Y.; Chen S.; Liu J.; Wang Y.; Li F.; He X.; Carey L.B.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:43
英文摘要	Most genetic changes have negligible reversion rates. As most mutations that confer resistance to an adverse condition (e.g., drug treatment) also confer a growth defect in its absence, it is challenging for cells to genetically adapt to transient environmental changes. Here, we identify a set of rapidly reversible drug-resistance mutations in Schizosaccharomyces pombe that are caused by microhomology-mediated tandem duplication (MTD) and reversion back to the wild-type sequence. Using 10,000× coverage whole-genome sequencing, we identify nearly 6,000 subclonal MTDs in a single clonal population and determine, using machine learning, how MTD frequency is encoded in the genome. We find that sequences with the highest-predicted MTD rates tend to generate insertions that maintain the correct reading frame, suggesting that MTD formation has shaped the evolution of coding sequences. Our study reveals a common mechanism of reversible genetic variation that is beneficial for adaptation to environmental fluctuations and facilitates evolutionary divergence. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Drug resistance; Genome evolution; Mutations; Sequencing; Yeast
语种	英语
scopus关键词	fungal DNA; adaptation; antifungal resistance; drug effect; fungal genome; gene expression regulation; genetic variation; genetics; machine learning; molecular evolution; mutation; physiology; reading frame; Schizosaccharomyces; segmental duplication; tandem repeat; whole genome sequencing; Adaptation, Physiological; DNA, Fungal; Drug Resistance, Fungal; Evolution, Molecular; Genetic Variation; Genome, Fungal; Machine Learning; Mutagenesis, Insertional; Mutation; Reading Frames; Schizosaccharomyces; Segmental Duplications, Genomic; Tandem Repeat Sequences; Whole Genome Sequencing
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251002
作者单位	The MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China; Center for Quantitative Biology, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China; State Key Laboratory of Plant Physiology and Biochemistry, China Agricultural University, Beijing, 100193, China
推荐引用方式 GB/T 7714	Dan L.,Li Y.,Chen S.,et al. A rapidly reversible mutation generates subclonal genetic diversity and unstable drug resistance[J],2021,118(43).
APA	Dan L..,Li Y..,Chen S..,Liu J..,Wang Y..,...&Carey L.B..(2021).A rapidly reversible mutation generates subclonal genetic diversity and unstable drug resistance.Proceedings of the National Academy of Sciences of the United States of America,118(43).
MLA	Dan L.,et al."A rapidly reversible mutation generates subclonal genetic diversity and unstable drug resistance".Proceedings of the National Academy of Sciences of the United States of America 118.43(2021).