English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Divergent allele advantage at human MHC Genes: signatures of past and ongoing selection

Pierini, F., & Lenz, T. L. (2018). Divergent allele advantage at human MHC Genes: signatures of past and ongoing selection. Molecular Biology and Evolution, 35(9), 2145-2158. doi:10.1093/molbev/msy116.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0001-9710-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0002-4C8A-E
Genre: Journal Article

Files

show Files

Locators

show
hide
Locator:
Link (Publisher version)
Description:
http://creativecommons.org/licenses/by-nc/4.0/

Creators

show
hide
 Creators:
Pierini, Federica1, Author              
Lenz, Tobias L.1, Author              
Affiliations:
1Emmy Noether Research Group Evolutionary Immunogenomics, Department Evolutionary Ecology, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_2068286              

Content

show
hide
Free keywords: HLA; balancing selection; heterozygote advantage; pathogen-mediated selection; human evolution
 Abstract: The highly polymorphic genes of the major histocompatibility complex (MHC) play a key role in adaptive immunity. Divergent allele advantage, a mechanism of balancing selection, is proposed to contribute to their exceptional polymorphism. It assumes that MHC genotypes with more divergent alleles allow for broader antigen-presentation to immune effector cells, by that increasing immunocompetence. However, the direct correlation between pairwise sequence divergence and the corresponding repertoire of bound peptides has not been studied systematically across different MHC genes. Here, we investigated this relationship for five key classical human MHC genes (human leukocyte antigen; HLA-A, -B, -C, -DRB1, and -DQB1), using allele-specific computational binding prediction to 118,097 peptides derived from a broad range of human pathogens. For all five human MHC genes, the genetic distance between two alleles of a heterozygous genotype was positively correlated with the total number of peptides bound by these two alleles. In accordance with the major antigen-presentation pathway of MHC class I molecules, HLA-B and HLA-C alleles showed particularly strong correlations for peptides derived from intracellular pathogens. Intriguingly, this bias coincides with distinct protein compositions between intra- and extracellular pathogens, possibly suggesting adaptation of MHC I molecules to present specifically intracellular peptides. Eventually, we observed significant positive correlations between an allele’s average divergence and its population frequency. Overall, our results support the divergent allele advantage as a meaningful quantitative mechanism through which pathogen-mediated selection leads to the evolution of MHC diversity.

Details

show
hide
Language(s): eng - English
 Dates: 2018-06-082018-09-01
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1093/molbev/msy116
BibTex Citekey: doi:10.1093/molbev/msy116
 Degree: -

Event

show

Legal Case

show

Project information

show hide
Project name : -
Grant ID : LE 2593/3-1
Funding program : DFG
Funding organization : -

Source 1

show
hide
Title: Molecular Biology and Evolution
  Other : Mol. Biol. Evol.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Oxford : Oxford University Press
Pages: - Volume / Issue: 35 (9) Sequence Number: - Start / End Page: 2145 - 2158 Identifier: ISSN: 0737-4038
CoNE: /journals/resource/954925536119