Origin and evolution of the major histocompatibility complex class I region in eutherian mammals

Abstract

Major histocompatibility complex (MHC) genes in vertebrates are vital in defending against pathogenic infections. To gain new insights into the evolution of MHC Class I (MHCI) genes and test competing hypotheses on the origin of the MHCI region in eutherian mammals, we studied available genome assemblies of nine species in Afrotheria, Xenarthra, and Laurasiatheria, and successfully characterized the MHCI region in six species. The following numbers of putatively functional genes were detected: in the elephant, four, one, and eight in the extended class I region, and κ and β duplication blocks, respectively; in the tenrec, one in the κ duplication block; and in the four bat species, one or two in the β duplication block. Our results indicate that MHCI genes in the κ and β duplication blocks may have originated in the common ancestor of eutherian mammals. In the elephant, tenrec, and all four bats, some MHCI genes occurred outside the MHCI region, suggesting that eutherians may have a more complex MHCI genomic organization than previously thought. Bat‐specific three‐ or five‐amino‐acid insertions were detected in the MHCI α1 domain in all four bats studied, suggesting that pathogen defense in bats relies on MHCIs having a wider peptide‐binding groove, as previously assayed by a bat MHCI gene with a three‐amino‐acid insertion showing a larger peptide repertoire than in other mammals. Our study adds to knowledge on the diversity of eutherian MHCI genes, which may have been shaped in a taxon‐specific manner.

Can extreme MHC class I diversity be a feature of a wide geographic range? The example of Seba’s short-tailed bat (Carollia perspicillata)

“…The same might be true for Chiroptera, as the pattern of indels in the MHC genes is similar between these two evolutionary divergent groups. For bats, length variation (3 and 5 amino acid indels) has been reported in the MHC class I genes of the black flying fox (Pteropus alecto), and in the Chinese horseshoe bat (Rhinolophus sinicus), the common vampire bat (Desmodus rotundus) the great roundleaf bat (Hipposideros armiger) and in the natal long-fingered bat (Miniopterus natalensis) Abduriyim et al 2019). The indels of the C. perspicillata alleles align to the same location as the indels in the other bat species.…”

“…The indels of the C. perspicillata alleles align to the same location as the indels in the other bat species. Compared to eutherian mammals other than bats, they apparently code for alleles with longer antigen binding domains (Abduriyim et al 2019). This suggests a common characteristic or evolutionary important trait in bats: it may cause an increased binding spectrum, as a longer allele (3-codon indel allele Ptal-N01:01) present antigens with a broader length range than shorter MHC class I molecules from other mammals .…”

Antigenic variation of SARS-CoV-2 in response to immune pressure

“…In fact, all these viruses, with the exclusion of SARS-CoV, were sampled from bats. Thus, whereas structural/functional constraints are expected to be maintained across long evolutionary time frames, the pressure exerted by the human cell-mediated immune response is not, as, in different species, antigen processing within host cells results in the preferential presentation of diverse viral epitopes to T lymphocytes depending on the MHC gene repertoire and on distinct preferences of the antigen processing pathway (Abduriyim et al, 2019;Burgevin et al, 2008;Hammer et al, 2007; Lu, Dan AND Liu, Kefang AND Zhang, Di AND Yue, Can AND Lu, Qiong AND Cheng, Hao AND Wang, Liang AND Chai, Yan AND Qi, Jianxun AND Wang, Lin-Fa AND Gao, George F. AND Liu,William J., 2019;Wynne et al, 2016). Conversely, epitopes for antibodies tend to be conserved across species (Tse et al, 2017;Wiehe et al, 2014) and consequently the selective pressure acting on these positions is expected to be constant across time and hosts.…”

The impact of bottlenecks and inbreeding on the genome of the endangered Pyrenean desman

“…For the heterozygous sequences, we selected the assembled sequence. Alignments at the amino acid level of these sequences together with those from other mammals (Abduriyim et al 2019), including Condylura cristata and a selection of human genes, were generated with MAFFT v7.464 (Katoh and Standley 2013) and processed with Gblocks v0.91 (Castresana 2000) to remove poorly aligned positions using low stringency conditions (minimum length of a block of 5 and allowing positions with gaps in half the number of sequences). Then, a maximum-likelihood phylogenetic tree was reconstructed with RAxML v8.2.12, using a JTT model of amino acid substitution and a gamma distribution of evolutionary rates (Stamatakis 2014).…”

“…Proteins that directly interact with the environment are particularly interesting in the context of genetic diversity as these require a high degree of inter-and intra-locus variability to function properly. Two protein families are key in this regard: the major histocompatibility complex (MHC), which is one of the principal components of the immune system (Abduriyim et al 2019;Radwan et al 2020); and the olfactory receptors (OR), which involves the largest multigene family in mammals (Hughes et al 2018). Due to balancing selection, a huge diversity of alleles is found in some MHC genes, consequently raising heterozygosity in these particular loci (Vandiedonck and Knight 2009).…”