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

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Penman, Bridget S. and Gupta, Sunetra (2018) Detecting signatures of past pathogen selection on human HLA loci : are there needles in the haystack? Parasitology , 145 (6). pp. 731-739. doi:10.1017/S0031182017001159

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Official URL: http://dx.doi.org/10.1017/S0031182017001159

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Abstract

Human Leukocyte 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.

Item Type: Journal Article
Subjects: Q Science > QR Microbiology
Divisions: Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): HLA histocompatibility antigens, Host-parasite relationships, Evolutionary genetics, Immunogenetics
Journal or Publication Title: Parasitology
Publisher: Cambridge University Press
ISSN: 0031-1820
Official Date: May 2018
Dates:
DateEvent
May 2018Published
15 August 2017Available
1 June 2017Accepted
Volume: 145
Number: 6
Page Range: pp. 731-739
DOI: 10.1017/S0031182017001159
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Funder: Seventh Framework Programme (European Commission) (FP7)
Grant number: 268904 (FP7)

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