Comparative Genomics of the Major Histocompatibility Complex (MHC) of Felids

Abstract

This review summarizes the current knowledge on the major histocompatibility complex (MHC) of the family Felidae. This family comprises an important domestic species, the cat, as well as a variety of free-living felids, including several endangered species. As such, the Felidae have the potential to be an informative model for studying different aspects of the biological functions of MHC genes, such as their role in disease mechanisms and adaptation to different environments, as well as the importance of genetic diversity for conservation issues in free-ranging or captive populations. Despite this potential, the current knowledge on the MHC in the family as a whole is fragmentary and based mostly on studies of the domestic cat and selected species of big cats. The overall structure of the domestic cat MHC is similar to other mammalian MHCs following the general scheme “centromere-MHC class I-MHC class III-MHC class II” with some differences in the gene contents. An unambiguously defined orthologue of the non-classical class I HLA-E gene has not been identified so far and the class II DQ and DP genes are missing or pseudogenized, respectively. A comparison with available genomes of other felids showed a generally high level of structural and sequence conservation of the MHC region. Very little and fragmentary information on in vitro and/or in vivo biological functions of felid MHC genes is available. So far, no association studies have indicated effects of MHC genetic diversity on a particular disease. No information is available on the role of MHC class I molecules in interactions with Natural Killer (NK) cell receptors or on the putative evolutionary interactions (co-evolution) of the underlying genes. A comparison of complex genomic regions encoding NK cell receptors (the Leukocyte Receptor Complex, LRC and the Natural Killer Cell Complex, NKC) in the available felid genomes showed a higher variability in the NKC compared to the LRC and the MHC regions. Studies of the genetic diversity of domestic cat populations and/or specific breeds have focused mainly on DRB genes. Not surprisingly, higher levels of MHC diversity were observed in stray cats compared to pure breeds, as evaluated by DRB sequencing as well as by MHC-linked microsatellite typing. Immunogenetic analysis in wild felids has only been performed on MHC class I and II loci in tigers, Namibian leopards and cheetahs. This information is important as part of current conservation tasks to assess the adaptive potential of endangered wild species at the human-wildlife interface, which will be essential for preserving biodiversity in a functional ecosystem.

The immunogenomic landscape of cattle

“…The MHC genes mainly contain two clusters, MHC class I and MHC class II (Petersdorf and O'HUigin, 2019), and by acquiring the seamless sequence of this gene locus, we were able to annotate the MHC genes coordinately. The cattle contain six classical MHC I genes (BoLA 1-6) with high polymorphism and ten non-classical MHC I genes (NC1-10) that show limited polymorphism (Plasil et al, 2022). Classical MHC I genes located at the 3'end of the entire BoLA region.…”

Unraveling Genome- and Immunome-wide Genetic Diversity in Jaguars (Panthera onca): Implications for Targeted Conservation

“…Few studies acknowledge this connection and focus on immune response genes and their implications for adaptability, especially in wild felids. While diversity in investigated TLR genes was lower in modern Southern African cheetahs than in African leopards 31 , a comparison of complex immune genomic regions in wild and domestic felids showed a general higher variability in natural killer gene complex (NKC) than in major histocompatibility complex (MHC) encoding genes 32 .…”

MHC Architecture in Amphibians—Ancestral Reconstruction, Gene Rearrangements, and Duplication Patterns

“…For example, in humans, the core MHC region is spread over 4-Mb fragment of chromosome 6 and contains classical MHC genes (MHC-Ia and MHC-II), MHC region antigen-processing genes encoding proteins involved in peptide processing and loading (PSMBs, TAPs, and TAPBP), and other MHC region genes (located in the MHC region, but not directly involved in antigen processing, loading, and presentation), which are clustered into three main subregions (MHC class I, class III, and class II) ( Shiina et al 2017 ). This general pattern of MHC organization is relatively conserved among eutherian mammals ( de Sá et al 2019 ; Li, Chen, et al 2019 ; Plasil et al 2022 ), although both MHC-I and MHC-II regions have been subject to some lineage-specific reorganizations. For example, DP (MHC-II) genes have been replaced by DI/DY genes in ruminants ( Andersson et al 1988 ; Li, Chen, et al 2019 ), while DQ and DR genes have been deleted and expanded, respectively, in felines ( Yuhki et al 2003 ; Plasil et al 2022 ).…”

“…This general pattern of MHC organization is relatively conserved among eutherian mammals ( de Sá et al 2019 ; Li, Chen, et al 2019 ; Plasil et al 2022 ), although both MHC-I and MHC-II regions have been subject to some lineage-specific reorganizations. For example, DP (MHC-II) genes have been replaced by DI/DY genes in ruminants ( Andersson et al 1988 ; Li, Chen, et al 2019 ), while DQ and DR genes have been deleted and expanded, respectively, in felines ( Yuhki et al 2003 ; Plasil et al 2022 ). In contrast, a large chromosomal inversion has been inferred to happen in the ancestors of Cetruminantia, dividing MHC class II into two subregions, as shown in both ruminants ( Li, Chen, et al 2019 ) and cetaceans ( de Sá et al 2019 ).…”