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The Missing Expression Level-Evolutionary Rate Anticorrelation in Viruses Does Not Support Protein Function as a Main Constraint on Sequence Evolution.
Wei, Changshuo; Chen, Yan-Ming; Chen, Ying; Qian, Wenfeng.
  • Wei C; State Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Beijing, China.
  • Chen YM; University of Chinese Academy of Sciences, Beijing, China.
  • Chen Y; State Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Beijing, China.
  • Qian W; University of Chinese Academy of Sciences, Beijing, China.
Genome Biol Evol ; 13(4)2021 04 05.
Article in English | MEDLINE | ID: covidwho-1387877
ABSTRACT
One of the central goals in molecular evolutionary biology is to determine the sources of variation in the rate of sequence evolution among proteins. Gene expression level is widely accepted as the primary determinant of protein evolutionary rate, because it scales with the extent of selective constraints imposed on a protein, leading to the well-known negative correlation between expression level and protein evolutionary rate (the E-R anticorrelation). Selective constraints have been hypothesized to entail the maintenance of protein function, the avoidance of cytotoxicity caused by protein misfolding or nonspecific protein-protein interactions, or both. However, empirical tests evaluating the relative importance of these hypotheses remain scarce, likely due to the nontrivial difficulties in distinguishing the effect of a deleterious mutation on a protein's function versus its cytotoxicity. We realized that examining the sequence evolution of viral proteins could overcome this hurdle. It is because purifying selection against mutations in a viral protein that result in cytotoxicity per se is likely relaxed, whereas purifying selection against mutations that impair viral protein function persists. Multiple analyses of SARS-CoV-2 and nine other virus species revealed a complete absence of any E-R anticorrelation. As a control, the E-R anticorrelation does exist in human endogenous retroviruses where purifying selection against cytotoxicity is present. Taken together, these observations do not support the maintenance of protein function as the main constraint on protein sequence evolution in cellular organisms.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Proteins / Evolution, Molecular / Endogenous Retroviruses / SARS-CoV-2 Type of study: Experimental Studies / Observational study / Prognostic study Limits: Animals / Humans Language: English Journal subject: Biology / Molecular Biology Year: 2021 Document Type: Article Affiliation country: GBE

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Proteins / Evolution, Molecular / Endogenous Retroviruses / SARS-CoV-2 Type of study: Experimental Studies / Observational study / Prognostic study Limits: Animals / Humans Language: English Journal subject: Biology / Molecular Biology Year: 2021 Document Type: Article Affiliation country: GBE