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SARS-CoV-2 continuously optimizes its codon usage to adapt to human lung environment.

Yinglian Wang1,2, Zhenhua Li3,4, Xiuxiu Wang5

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SARS-CoV-2 continuously optimizes its codon usage for better proliferation in human lungs. Synonymous mutations increasing codon optimality are favored by natural selection, impacting viral fitness.

Keywords:
Allele frequencyCodon usageEvolutionLungSARS-CoV-2

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Area of Science:

  • Virology
  • Genomics
  • Evolutionary Biology

Background:

  • Viral replication relies on host cell resources, with RNA translation rate, governed by codon usage, being a critical bottleneck.
  • Adapting codon usage to that of the host enhances viral proliferation.
  • SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) evolution involves synonymous mutations affecting its lifecycle.

Discussion:

  • Synonymous mutations in SARS-CoV-2 were analyzed for their impact on Relative Synonymous Codon Usage (RSCU).
  • Mutations increasing RSCU (delta RSCU > 0) in human lung tissue were found to be positively selected, indicated by increasing allele frequency (AF) over time.
  • This suggests SARS-CoV-2 actively optimizes its codon usage for replication efficiency in the human respiratory system.

Key Insights:

  • For the first time, allele frequency dynamics demonstrate SARS-CoV-2's ongoing codon usage optimization for human lung adaptation.
  • Synonymous mutations are not neutral and can significantly alter viral fitness.
  • The study highlights the importance of considering synonymous mutations in viral evolution and pandemic response.

Outlook:

  • Further research should investigate SARS-CoV-2 adaptation in other human tissues.
  • Understanding codon usage adaptation can inform the development of antiviral strategies.
  • Continuous monitoring of synonymous mutations is crucial for tracking viral evolution during pandemics.