Polymorphic sites preferentially avoid co-evolving residues in MHC class I proteins

Major histocompatibility complex class I (MHC-I) molecules are critical to adaptive immune defence mechanisms in vertebrate species and are encoded by highly polymorphic genes. Polymorphic sites are located close to the ligand-binding groove and entail MHC-I alleles with distinct binding specificities. Some efforts have been made to investigate the relationship between polymorphism and protein stability. However, less is known about the relationship between polymorphism and MHC-I co-evolutionary constraints. Using Direct Coupling Analysis (DCA) we found that co-evolution analysis accurately pinpoints structural contacts, although the protein family is restricted to vertebrates and comprises less than five hundred species, and that the co-evolutionary signal is mainly driven by cross-species changes, and not intra-species polymorphism. Moreover, we show that polymorphic sites in human preferentially avoid co-evolving residues, as well as residues involved in protein stability. These results suggest that sites displaying high polymorphism may also have been selected during vertebrates’ evolution to avoid those under co-evolutionary constraints and thereby maximize their mutability.See it on Scoop.it, via Viruses, Immunology & Bioinformatics from Virology.uvic.ca
Polymorphic sites preferentially avoid co-evolving residues in MHC class I proteins
Source: Viral Bioinformatics