Evolution and organization of MHC II genes in Harbour porpoises:
insights from long-read cetacean genome assemblies, whole genome
re-sequencing and locus-specific genotyping
Abstract
The Major Histocompatibility Complex (MHC) is a central element in the
vertebrate immune system. While MHC genes are a common target of
conservation genomic studies, it has been challenging to reliably
amplify locus-specific alleles, which is especially problematic when
studying endangered lineages, like some Harbour porpoise (Phocoena
phocoena) populations and subspecies. Here, we manually annotated all
MHC II genes in the Harbour porpoise genome, and genotyped every exon 2
in 94 individuals spanning six geographical regions, including the
endangered Black Sea porpoise subspecies (Phocoena phocoena relicta) and
the endangered Proper Baltic Sea population of the North Atlantic
subspecies (P. p. phocoena). We performed gene-wise analyses of
diversity and selection, and put the results into perspective with 24
available Harbour porpoise genomes. Furthermore, we characterized all
MHC II genes in 19 available long-read cetacean and terrestrial
outgroups genomes to study the MHC II evolution across the cetacean
diversification. From the 10 MHC II loci annotated in the Harbour
porpoise genome, two (DRB1 and DQB) exhibited inflated allelic diversity
and signatures of positive selection. Interestingly, DRB genes followed
different evolutionary trajectories in mysticetes and odontocetes. Our
results have significant conservation implications since we identified
reduced MHC II diversity in the endangered Black Sea subspecies, and
provide a case study for reliable MHC II genotyping in other species.
Further, our study demonstrates the need for long-read genomes to
understand the genomic architecture of MHC and to accurately assess its
diversity and evolution.