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The Missing Expression Level-Evolutionary Rate Anticorrelation in Viruses Does Not Support Protein Function as a Main

Changshuo Wei1,2, Yan-Ming Chen1,2, Ying Chen1

  • 1State Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Beijing, China.

Genome Biology and Evolution
|March 13, 2021
PubMed
Summary
This summary is machine-generated.

Viral protein evolution rates do not correlate with gene expression levels, challenging the widely accepted expression-rate (E-R) anticorrelation. This suggests protein function, not cytotoxicity, is the primary driver of sequence evolution in cellular organisms.

Keywords:
avoidance of cytotoxicitygene expression levelmaintenance of protein functionprotein evolutionary rateprotein homeostasisthe E–R anticorrelation

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Area of Science:

  • Molecular evolutionary biology
  • Protein evolution
  • Genomics

Background:

  • The rate of protein sequence evolution varies significantly among proteins.
  • Gene expression level is considered the main factor influencing protein evolutionary rate, leading to the expression-rate (E-R) anticorrelation.
  • Selective constraints, such as maintaining protein function or avoiding cytotoxicity, are hypothesized to cause the E-R anticorrelation.

Purpose of the Study:

  • To empirically test the relative importance of protein function versus cytotoxicity in driving selective constraints.
  • To investigate the E-R anticorrelation in viral proteins to distinguish between these hypotheses.

Main Methods:

  • Comparative sequence analysis of viral proteins, including SARS-CoV-2 and ten other virus species.
  • Analysis of human endogenous retroviruses as a control.
  • Examining the relationship between gene expression levels and protein evolutionary rates.

Main Results:

  • A complete absence of the E-R anticorrelation was observed in the analyzed viral proteins.
  • The E-R anticorrelation was present in human endogenous retroviruses, where selection against cytotoxicity is expected.
  • These findings indicate relaxed purifying selection against cytotoxicity in viral proteins.

Conclusions:

  • The study challenges the prevailing hypothesis that gene expression level is the primary determinant of protein evolutionary rates in cellular organisms.
  • The results suggest that the maintenance of protein function, rather than avoidance of cytotoxicity, is the main constraint on protein sequence evolution.
  • Viral protein evolution provides a unique model system for dissecting the forces shaping sequence evolution.