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

Published online by Cambridge University Press:  15 August 2017

Bridget S. Penman*
School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK
Sunetra Gupta
Department of Zoology, University of Oxford, Oxford, OX1 3PS, UK
Author for correspondence: Bridget S. Penman, E-mail:


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.

Research Article
Copyright © Cambridge University Press 2017 

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