Lineage pattern, trans-species polymorphism, and selection pressure among the major lineages of feline Mhc-DRB peptide-binding region

Abstract

The long-term evolution of major histocompatibility complex (MHC) involves the birth-and-death process and independent divergence of loci during episodes punctuated by natural selection. Here, we investigated the molecular signatures of natural selection at exon-2 of MHC class II DRB gene which includes a part of the peptide-binding region (PBR) in seven of eight putative extant Felidae lineages. The DRB alleles in felids can be mainly divided into five lineages. Signatures of trans-species polymorphism among major allelic lineages indicate that balancing selection has maintained the MHC polymorphism for a long evolutionary time. Analysis based on maximum likelihood models of codon substitution revealed overall purifying selection acting on the feline DRB. Sites that have undergone positive selection and those that are under divergent selective pressure among lineages were detected and found to fall within the putative PBR. This study increased our understanding of the nature of selective forces acting on DRB during feline radiation.

Retention of functional variation despite extreme genomic erosion: MHC allelic repertoires in the Lynx genus

“…As Wei et al [28] found for several felids in MHCII-DRB, we also detected instances of TSP between lynxes and other distant felids for both MHCI and MHCII-DRB (Additional file 1: Tables S8-S13). TSP across such large divergence times are unlikely due only to neutral processes and are thus more likely the consequence of long-term balancing selection or convergent evolution (i.e., balanced TSP).…”

“…The four species in the Lynx genus showed a high level of shared MHC polymorphisms across species, a feature in common with other recently diverged taxa [28, 29, 50, 51]. As Wei et al [28] found for several felids in MHCII-DRB, we also detected instances of TSP between lynxes and other distant felids for both MHCI and MHCII-DRB (Additional file 1: Tables S8-S13).…”

“…However, we did not find signatures of long-term positive selection in the form of an increased d N /d S ratio at ABS for any MHC family. Contrastingly, such positive selection signals were previously described in analyses of MHCI in cheetah [30], bengal tiger [32] and leopard [31], and for MHCII-DRB in eight different Felidae lineages [28], cheetah [30], but not in bengal tiger [32], leopard [31] or Eurasian lynx [29]. Interestingly, for MHCI we found d S at the ABS to be much larger than d S at non-ABS, this indicates that the ABS regions are older than non-ABS and points to positive selection acting in presence of recurrent gene conversion events [45].…”

“…In felids MHC genes have received special attention due to the role of domestic cat as a model for human diseases [24–27] and because of its possible impact on endangered wild felid conservation, including the paradigmatic case of the cheetah [18, 28–32]. …”

Molecular polymorphism of MHC-DRB gene and genetic diversity analysis of captive forest musk deer (Moschus berezovskii)

“…The major histocompatibility complex (MHC), an adaptive immune system, is one of the most important elements in immune system for nearly all vertebrates (Wei et al, 2010). The MHC is a large gene family encoding transmembrane proteins, which are responsible for pathogen peptides recognition and displaying them on the cell surface for recognition by the appropriate T-cells (Roche and Furuta, 2015).…”