Expansion of MHC-IIB Has Constrained the Evolution of MHC-IIA in Passerines

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Abstract
The major histocompatibility complex (MHC) is central in adaptive immunity, with the highly polymorphic MHC genes encoding antigen-presenting molecules. Two MHC class II (MHC-II) loci, DA1 and DA2, pre-date the radiation of extant birds and persist throughout much of the avian phylogeny. Within each locus, the MHC-II molecules are encoded by A- (DAA) and B- (DAB) genes, which are arranged in A–B dyads. However, in passerines (order Passeriformes), the DA2 locus has been lost and the ancestral A–B dyad at the DA1 locus has been replaced by a putatively single A-gene (DAA1) and an array of highly polymorphic B-genes (DAB1). In this study, we genotyped the DAA1 gene of 15 passerine species and confirmed that passerines possess just one copy of DAA1. We then compared selection patterns in DAA1 between passerines and non-passerines and found that exon 2, which encodes the antigen-presenting domain, has been subject to weaker positive selection and stronger negative selection in passerines compared with non-passerines. Additional comparisons showed that the patterns of selection in the passerine DAA1 gene are unlikely to be related to the loss of the DA2 locus. Instead, our findings suggest that the expansion of DAB1 (MHC-IIB) has imposed an evolutionary constraint on the passerine DAA1 (MHC-IIA) gene. We speculate that this constraint may be the result of each DAA1 chain having to form heterodimers with many different DAB1 chains.
Funding Information
  • Swedish Research Council (2020-04285)

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