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DOI	10.1038/s41559-021-01578-x
	Expression level is a major modifier of the fitness landscape of a protein coding gene
	Wu Z.; Cai X.; Zhang X.; Liu Y.; Tian G.-B.; Yang J.-R.; Chen X.
发表日期	2022
ISSN	2397-334X
起始页码	103
结束页码	115
卷号	6 期号:1
英文摘要	The phenotypic consequence of a genetic mutation depends on many factors including the expression level of a gene. However, a comprehensive quantification of this expression effect is still lacking, as is a further general mechanistic understanding of the effect. Here, we measured the fitness effect of almost all (>97.5%) single-nucleotide mutations in GFP, an exogenous gene with no physiological function, and URA3, a conditionally essential gene. Both genes were driven by two promoters whose expression levels differed by around tenfold. The resulting fitness landscapes revealed that the fitness effects of at least 42% of all single-nucleotide mutations within the genes were expression dependent. Although only a small fraction of variation in fitness effects among different mutations can be explained by biophysical properties of the protein and messenger RNA of the gene, our analyses revealed that the avoidance of stochastic molecular errors generally underlies the expression dependency of mutational effects and suggested protein misfolding as the most important type of molecular error among those examined. Our results therefore directly explained the slower evolution of highly expressed genes and highlighted cytotoxicity due to stochastic molecular errors as a non-negligible component for understanding the phenotypic consequence of mutations. ? 2021, The Author(s), under exclusive licence to Springer Nature Limited.
语种	英语
scopus关键词	protein; mutation; reproductive fitness; Genetic Fitness; Mutation; Proteins
来源期刊	Nature Ecology & Evolution
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/257236
作者单位	Department of Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China; School of Medicine, Xizang Minzu University, Xianyang, China
推荐引用方式 GB/T 7714	Wu Z.,Cai X.,Zhang X.,et al. Expression level is a major modifier of the fitness landscape of a protein coding gene[J],2022,6(1).
APA	Wu Z..,Cai X..,Zhang X..,Liu Y..,Tian G.-B..,...&Chen X..(2022).Expression level is a major modifier of the fitness landscape of a protein coding gene.Nature Ecology & Evolution,6(1).
MLA	Wu Z.,et al."Expression level is a major modifier of the fitness landscape of a protein coding gene".Nature Ecology & Evolution 6.1(2022).