Extensive Trans-Species Polymorphism at the Major Histocompatibility Complex in Primates
Authors: Alyssa Lyn Fortier; Jonathan Pritchard
Affiliation: Stanford University
Keywords: Phylogenetics, Macroevolution, and Biogeography
Genes within the Major Histocompatibility Complex (MHC) exhibit exceptional diversity, with thousands of alleles per gene in humans and other primates. Even distantly-related species appear to share similar alleles, pointing to possible long-term balancing selection at this locus. The MHC may even exhibit trans-species polymorphism (TSP), an extremely rare phenomenon in which alleles between species are more similar than alleles within species. Although previous work has suggested TSP at this locus, most have examined sequences from only a single exon, are limited to a handful of species, or fail to quantify support for these trans-species clades. Additionally, most studies on TSPs lack the functional context needed to interpret the results. We aimed to comprehensively characterize the nature and extent of TSP at the classical MHC genes. Using modern data from entire genes and across the primates, we find strong support for TSP in all six classical genes, including between humans and old-world monkeys (OWM) in HLA-DRB1, and even between humans and new-world monkeys (NWM) in HLA-DQB1. Additionally, rapidly-evolving amino acids within each gene are concordant with disease- and immune-phenotype-associated amino acids from the literature. Taken together, definitive TSP and functionally-relevant rapidly-evolving sites suggest complex and competing selective forces and a possible trade-off between disease susceptibility and infection resistance.