Detecting signatures of past pathogen selection on human HLA loci: are there needles in the haystack?

Authored by Sunetra Gupta, Bridget S Penman

Date Published: 2018

DOI: 10.1017/s0031182017001159

Sponsors: European Union

Platforms: No platforms listed

Model Documentation: Other Narrative

Model Code URLs: Model code not found

Abstract

Human leucocyte antigens (HLAs) are responsible for the display of peptide fragments for recognition by T-cell receptors. The gene family encoding them is thus integral to human adaptive immunity, and likely to be under strong pathogen selection. Despite this, it has proved difficult to demonstrate specific examples of pathogen-HLA coevolution. Selection from multiple pathogens simultaneously could explain why the evolutionary signatures of particular pathogens on HLAs have proved elusive. Here, we present an individual-based model of HLA evolution in the presence of two mortality-causing pathogens. We demonstrate that it is likely that individual pathogen species causing high mortality have left recognizable signatures on the HLA genomic region, despite more than one pathogen being present. Such signatures are likely to exist at the whole-population level, and involve haplotypic combinations of HLA genes rather than single loci.

Tags

Human evolution Virus-infection Resistance Genetic-variation Major histocompatibility complex Human leucocyte antigen (hla) Host pathogen coevolution Pathogen selection Sickle-cell trait Hiv-1 infection Negative epistasis Severe malaria C expression Mhc