Trade‐offs in expressed major histocompatibility complex diversity seen on a macroevolutionary scale among songbirds

Abstract

To survive organisms must defend themselves against pathogens. Classical Major Histocompatibility Complex (MHC) genes play a key role in pathogen defense by encoding molecules involved in pathogen recognition. MHC gene diversity influences the variety of pathogens individuals can recognize and respond to and has consequently been a popular genetic marker for disease resistance in ecology and evolution. However, MHC diversity is predominantly estimated using genomic DNA (gDNA) with little knowledge of expressed diversity. This limits our ability to interpret the adaptive significance of variation in MHC diversity, especially in species with very many MHC genes such as songbirds. Here, we address this issue using phylogenetic comparative analyses of the number of MHC class I alleles (MHC‐I diversity) in gDNA and complementary DNA (cDNA), that is, expressed alleles, across 13 songbird species. We propose three theoretical relationships that could be expected between genomic and expressed MHC‐I diversity on a macroevolutionary scale and test which of these are best supported. In doing so, we show that significantly fewer MHC‐I alleles than the number available are expressed, suggesting that optimal MHC‐I diversity could be achieved by modulating gene expression. Understanding the relationship between genomic and expressed MHC diversity is essential for interpreting variation in MHC diversity in an evolutionary context.

Avian blood parasite richness decreases with major histocompatibility complex class I loci number

“…The latter is also supported by the greatly accelerated MHC duplication rate in songbirds, which is unlikely to be the result of parasite-mediated selection alone [12]. Second, it is now known that significantly fewer MHC class I alleles are expressed than present in the genome [3], which is particularly concerning in species with highly duplicated MHC genes such as many songbirds [3,11,12]. Non-expressed MHC alleles ( pseudogenes) are particularly problematic while using genotyping methods relying on genomic DNA assembled from short segments [3], such as pyrosequencing, which potentially inflates estimated of copy numbers.…”

“…Second, it is now known that significantly fewer MHC class I alleles are expressed than present in the genome [3], which is particularly concerning in species with highly duplicated MHC genes such as many songbirds [3,11,12]. Non-expressed MHC alleles ( pseudogenes) are particularly problematic while using genotyping methods relying on genomic DNA assembled from short segments [3], such as pyrosequencing, which potentially inflates estimated of copy numbers. Consistently, pyrosequencing detected higher MHC loci than cloning in all species genotyped by both techniques.…”

“…We collected estimates of MHC-I diversity (i.e. loci number) from published databases [3,12,33]. In total, we compiled 81 different estimates of MHC-I diversity with corresponding blood parasite information (see final database in electronic supplementary material, table S1).…”

“…Several studies reported that a low number of MHC loci could represent the ancestral state in birds, and that the highest diversification in copy numbers occurred relatively late in the avian radiation, reaching its highest diversity in passerines [12]. While, parasite-mediated selection has been considered as the most prominent component driving MHC diversification [13], it is now widely accepted that in addition to the pathogen burden, sexual selection and risk of developing autoimmune diseases or immunopathologies may together shape the evolution of an optimal rather than maximal MHC diversity [3,4,[13][14][15].…”

“…Proteins encoded by the MHC genes ensure the immune presentation of a broad spectrum of peptides, both derived from the intracellular (class I proteins) or extracellular (class II proteins) space [2]. High-MHC diversity, reflected by high allele diversity or loci number, is often related to the ability to present a wider repertoire of antigens to the immune system, thus representing a genetic marker of disease resistance [3] but see [4]. Several, mutually non-exclusive hypotheses have been put forward to explain the © 2021 The Author(s) Published by the Royal Society.…”