Pathogen selection drives nonoverlapping associations between HLA loci
Penman, Bridget S
Buckee, Caroline O
Proceedings of the National Academy of Sciences
Penman et al. Freely available online through the PNAS open access option.
Pathogen-mediated selection is commonly invoked as an explanation for the exceptional polymorphism of the HLA gene cluster, but its role in generating and maintaining linkage disequilibrium between HLA loci is unclear. Here we show that pathogen-mediated selection can promote nonrandom associations between HLA loci. These associations may be distinguished from linkage disequilibrium generated by other population genetic processes by virtue of being nonoverlapping as well as nonrandom. Within our framework, immune selection forces the pathogen population to exist as a set of antigenically discrete strains; this then drives nonoverlapping associations between the HLA loci through which recognition of these antigens is mediated. We demonstrate that this signature of pathogen-driven selection can be observed in existing data, and propose that analyses of HLA population structure can be combined with laboratory studies to help us uncover the functional relationships between HLA alleles. In a wider coevolutionary context, our framework also shows that the inclusion of memory immunity can lead to robust cyclical dynamics across a range of host-pathogen systems.
European Research Council (ERC)
Biotechnology and Biological Sciences Research Council (BBSRC)
Christopher Welch Trust
notes: PMCID: PMC3845180
types: Journal Article; Research Support, Non-U.S. Gov't
This is an open access article freely available in ORE or by following the DOI link above. Please cite the published version.
Vol. 110, Issue 48, pp. 19645 - 19650
Place of publication