Limited MHC class II gene polymorphism in the West African chimpanzee is distributed maximally by haplotype diversity

Abstract

Chimpanzees have been used for some time as an animal model in research on immune-related diseases in humans. The major histocompatibility complex (MHC) region of the chimpanzee has also been the subject of studies in which the attention was mainly on the class I genes. Although full-length sequence information is available on the DRB region genes, such detailed information is lacking for the other class II genes and, if present, is based mainly on exon 2 sequences. In the present study, full-length sequencing was performed on DQ, DP, and DRA genes in a cohort of 67 pedigreed animals, thereby allowing a thorough analysis of the MHC class II repertoire. The results demonstrate that the number of MHC class II lineages and alleles is relatively low, whereas haplotype diversity (combination of genes/alleles on a chromosome) seems to have been maximised by crossing-over processes.

Comparative genetics of the major histocompatibility complex in humans and nonhuman primates

“…The IPD‐IMGT/HLA database (Robinson et al., 2015) currently comprises data on 5,907 HLA‐A , 7,126 HLA‐B , 5,709 ‐C , 168 HLA‐DPA1 , 1,537 HLA‐DPB1 , 229 HLA‐DQA1 , 1,795 HLA‐DQB1 , 29 HLA‐DRA and 3,331 HLA‐DRB alleles (numbers are according release 3.39.0). For common chimpanzees, individuals of P.t.verus , P.t.troglodytes and P.t.schweinfurthii populations were studied for their MHC repertoire (de Groot et al., 2000;Maibach et al., 2017;Otting, de Groot, & Bontrop, 2019;Wroblewski et al., 2015). One has to realize, however, that for NHP no commercial MHC typing kits are available, and the MHC genes are studied independently.…”

“…For the DRB region, in particular the total number of HLA‐DRB1 lineages exceeds the total number of Patr‐DRB1 lineages (Table 2). Chimpanzees only possess DRB1 alleles clustering into the HLA‐DRB1*03 , *07 and *10 lineage, and alleles clustering into the HLA‐DRB1*01 , *08 , *09 , *11 till *16 lineages have not been detected (de Groot et al., 2008, 2009;Otting et al., 2019). Moreover, the equivalent of the HLA‐DRB1*04 lineage, which is present in macaques and humans, and as such represents an old entity, was lost during chimpanzee evolution (de Groot et al., 2009).…”

“…The rapid evolution, however, hampered division of the HLA‐DPB1 alleles into distinct lineages, and most alleles received their own lineage name ( DPB1*01 to DPB1*999 ). In chimpanzees, only 34 DPB1 alleles are defined, which cluster into three distinct lineages (Otting et al., 2019). The mechanism of frequent exchange of sequence motifs, which is the hallmark for the HLA‐DPB genes, seems to be absent here.…”

“…Although chimpanzees appear to possess a limited MHC class II repertoire as compared to humans, recent work highlighted that the limited number of alleles present are distributed maximally across different haplotypes by means of crossing‐over processes. More in detail, in a group of chimpanzees ( P.t.verus ), which comprised 27 founders animals, a total number of 37 unique DPA‐DPB‐DQA‐DQB‐DRA‐DRB haplotypes have been defined (Otting et al., 2019).…”

Similar patterns of genetic diversity and linkage disequilibrium in Western chimpanzees (Pan troglodytes verus) and humans indicate highly conserved mechanisms of MHC molecular evolution

“…2). Note also that in chimpanzees, MHC class II diversity is particularly high at the haplotype level thanks to inter-locus recombinations despite important loss of variation at single genes due to the past selective sweep [104].…”