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

Details

Ressource 1Download: journal.pcbi.1006188.pdf (3706.46 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_C9940E7E30A3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Polymorphic sites preferentially avoid co-evolving residues in MHC class I proteins.
Journal
PLoS computational biology
Author(s)
Dib L., Salamin N., Gfeller D.
ISSN
1553-7358 (Electronic)
ISSN-L
1553-734X
Publication state
Published
Issued date
05/2018
Peer-reviewed
Oui
Volume
14
Number
5
Pages
e1006188
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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 inter-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 have been selected during vertebrates' evolution to avoid co-evolutionary constraints and thereby maximize their mutability.
Keywords
Animals, Binding Sites/genetics, Evolution, Molecular, Histocompatibility Antigens Class I/chemistry, Histocompatibility Antigens Class I/genetics, Histocompatibility Antigens Class I/metabolism, Humans, Models, Molecular, Phylogeny, Polymorphism, Genetic/genetics, Protein Stability, Vertebrates/genetics
Pubmed
Web of science
Open Access
Yes
Create date
24/05/2018 17:03
Last modification date
20/08/2019 15:44
Usage data