Gorilla MHC class I gene and sequence variation in a comparative context

Abstract

Comparisons of MHC gene content and diversity among closely related species can provide insights into the evolutionary mechanisms shaping immune system variation. After chimpanzees and bonobos, gorillas are humans' closest living relatives; but in contrast, relatively little is known about the structure and variation of gorilla MHC class I genes (Gogo). Here, we combined long-range amplifications and long-read sequencing technology to analyze full-length MHC class I genes in 35 gorillas. We obtained 50 full-length genomic sequences corresponding to 15 Gogo-A alleles, 4 Gogo-Oko alleles, 21 Gogo-B alleles, and 10 Gogo-C alleles including 19 novel coding region sequences. We identified two previously undetected MHC class I genes related to Gogo-A and Gogo-B, respectively, thereby illustrating the potential of this approach for efficient and highly accurate MHC genotyping. Consistent with their phylogenetic position within the hominid family, individual gorilla MHC haplotypes share characteristics with humans and chimpanzees as well as orangutans suggesting a complex history of the MHC class I genes in humans and the great apes. However, the overall MHC class I diversity appears to be low further supporting the hypothesis that gorillas might have experienced a reduction of their MHC repertoire.

Keywords: Evolution; Gogo; Haplotypes; MHC genotyping; Next-generation sequencing; PacBio.

Fig. 1

Alignment of amino acid sequences of the alpha-1 and -2 domains of gorilla class I sequences. Identity to consensus sequence is denoted by a dash. For differences from the consensus sequence, the amino acid is shown. Highlighted in bold are previously unreported alleles. Gogo, Gorilla gorilla, Gobe, Gorilla beringei

Fig. 2

Phylogenetic tree constructed from full-length coding region sequences of MHC-A and -A-related genes. Relevant bootstrap values (≥70%) are shown. Previously described gorilla alleles identified in the present study are highlighted in bold. Newly identified alleles are underlined. (A2) and (A3) indicate the two phylogenetic A lineages, respectively. HLA human, Patr Pan troglodytes, Papa Pan paniscus, Gogo Gorilla gorilla, Popy Pongo pygmaeus

Fig. 3

Phylogenetic tree constructed from full-length coding region sequences of MHC-B and -C genes. Relevant bootstrap values (≥70%) are shown. Previously described gorilla alleles identified in the present study are highlighted in bold. Newly identified alleles are underlined. (B) and (C) indicate the phylogenetic clusters of the orthologous MHC-B and -C genes, respectively. HLA human, Patr Pan troglodytes, Papa Pan paniscus, Gogo Gorilla gorilla, Gobe Gorilla beringei, Popy Pongo pygmaeus

Fig. 4

Distribution of pairwise nucleotide differences between complete coding region sequences of MHC class I A, B, and C alleles in gorillas, chimpanzees, and humans. Gogo, Patr, and HLA distributions are shown in black, gray, and white, respectively. Gogo-Oko and Gogo-B*07 distributions are shown in dashed black, respectively. In the upper left corner, the number of alleles used for the calculation of the mean pairwise difference is shown

Fig. 5

Amino acid sequences of Gogo-B and -C alleles determining the KIR-binding epitope. Identity to consensus sequence is denoted by a dash. For differences from the consensus sequence, the amino acid is shown. Positions highlighted in green, blue, and red define the Bw4 epitope, the C1 and the C2 epitopes, respectively

Fig. 6

Simplified MHC class I A region haplotypes of humans and the great apes. White boxes represent the orthologous MHC-A gene whereas gray boxes represent the orthologous MHC-A-related gene

Fig. 7

Simplified MHC class I B and C region haplotypes of humans and the great apes. White boxes represent the orthologous MHC-C gene whereas light gray boxes represent the orthologous MHC-B gene. Dark gray boxes represent the orthologous MHC-B gene present only in gorillas and orangutans. Copy number variation at the MHC-B gene in orangutans is depicted by a question mark