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Mutation-driven parallel evolution in emergence of ACE2-utilizing sarbecoviruses
1Group of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Frontiers in Microbiology
|March 13, 2023
Summary
Three distinct ancestral sarbecovirus spike protein receptor-binding domains (RBDs) independently evolved the ability to bind human ACE2. This occurred through parallel mutations and intermediate forms, shedding light on early virus evolution.
Area of Science:
- Virology
- Evolutionary Biology
- Structural Biology
Background:
- Mutation and recombination are key drivers of viral evolution.
- Sarbecoviruses, including SARS-CoV and SARS-CoV-2, are a group of beta-coronaviruses with diverse ACE2 receptor usage.
- The origin of ACE2 binding in sarbecoviruses remains an evolutionary question.
Purpose of the Study:
- To investigate the evolutionary mechanisms behind ACE2 binding in sarbecoviruses.
- To elucidate how distinct sarbecovirus lineages acquired the ACE2 binding trait.
Main Methods:
- Phylogenetic analysis
- Ancestral sequence reconstruction
- Structural and functional assays
- Molecular dynamics simulations
Main Results:
- Evidence suggests three independent origins of ACE2 binding via parallel amino acid mutations.
- Evolutionary intermediates, involving loop extensions and point mutations, preceded ACE2 binding.
- Optimization of these intermediates led to the emergence of ACE2-binding RBDs in different sarbecovirus clades.
Conclusions:
- ACE2 binding in sarbecoviruses arose independently multiple times through convergent evolution.
- Understanding early mutation-driven evolution is crucial for sarbecovirus research.
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