The genomic architecture of the passerine MHC region: high repeat content and contrasting evolutionary histories of single copy and tandemly duplicated MHC genes

The Major Histocompatibility Complex (MHC) is of central importance to the
immune system, and an optimal MHC diversity is believed to maximize
pathogen elimination. Birds show substantial variation in MHC diversity,
ranging from few genes in most bird orders to very many genes in
passerines. Our understanding of the evolutionary trajectories of the MHC
in passerines is hampered by lack of data on genomic organization.
Therefore, we assemble and annotate the MHC genomic region of the great
reed warbler (Acrocephalus arundinaceus), using long-read sequencing and
optical mapping. The MHC region is large (>5.5Mb), characterized by
structural changes compared to hitherto investigated bird orders and shows
higher repeat content than the genome average. These features were
supported by analyses in three additional passerines. MHC genes in
passerines are found in two different chromosomal arrangements, either as
single copy MHC genes located among non-MHC genes, or as tandemly
duplicated tightly linked MHC genes. Some single copy MHC genes are old
and putative orthologs among species. In contrast tandemly duplicated MHC
genes are monophyletic within species and have evolved by simultaneous
gene duplication of several MHC genes. Structural differences in the MHC
genomic region among bird orders seem substantial compared to mammals and
have possibly been fuelled by clade-specific immune system adaptations.
Our study provides methodological guidance in characterizing complex
genomic regions, constitutes a resource for MHC research in birds, and
calls for a revision of the general belief that avian MHC has a conserved
gene order and small size compared to mammals.