Functional Constraint Profiling of a Viral Protein Reveals Discordance of Evolutionary Conservation and Functionality

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The analysis of sequence conservation is a common approach to identify functional residues within a protein. However, not all functional residues are conserved as natural evolution and species diversification permit continuous innovation of protein functionality through the retention of advantageous mutations. Non-conserved functional residues, which are often species-specific, may not be identified by conventional analysis of sequence conservation despite being biologically important. Here we described a novel approach to identify functional residues within a protein by coupling a high-throughput experimental fitness profiling approach with computational protein modeling. Our methodology is independent of sequence conservation and is applicable to any protein where structural information is available. In this study, we systematically mapped the functional residues on the influenza A PA protein and revealed that non-conserved functional residues are prevalent. Our results not only have significant implication on how functionality evolves during natural evolution, but also highlight the caveats when applying conservation-based approaches to identify functional residues within a protein.

Vyšlo v časopise: Functional Constraint Profiling of a Viral Protein Reveals Discordance of Evolutionary Conservation and Functionality. PLoS Genet 11(7): e32767. doi:10.1371/journal.pgen.1005310
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005310

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