Comparative genomics of the human, macaque and mouse major histocompatibility complex

Abstract

The MHC is a highly polymorphic genomic region that encodes the transplantation and immune regulatory molecules. It receives special attention for genetic investigation because of its important role in the regulation of innate and adaptive immune responses and its strong association with numerous infectious and/or autoimmune diseases. The MHC locus was first discovered in the mouse and for the past 50 years it has been studied most intensively in both mice and humans. However, in recent years the macaque species have emerged as some of the more important and advanced experimental animal models for biomedical research into MHC with important human immunodeficiency virus/simian immunodeficiency virus and transplantation studies undertaken in association with precise MHC genotyping and haplotyping methods using Sanger sequencing and next-generation sequencing. Here, in this special issue on 'Macaque Immunology' we provide a short review of the genomic similarities and differences among the human, macaque and mouse MHC class I and class II regions, with an emphasis on the association of the macaque class I region with MHC polymorphism, haplotype structure and function.

Keywords: haplotype; macaque; major histocompatibility complex; polymorphism.

Figure 1

Phylogenetic relationships between the human and five representative experimental animals. The time of divergence is on the Time Tree website (http://www.timetree.org/).

Figure 2

Gene map of the HLA genomic region. The MHC gene map corresponds to the genomic coordinates of 29 602 228 (GABBR1) to 33 410 226 (KIFC1) in the human genome GRCh38.p2 primary assembly of the NCBI map viewer. The regions separated by arrows show the HLA sub‐regions such as extended class I, class I, class III, classical class II and extended class II regions from telomere (left and top side) to centromere (right and bottom side). Blue and pink boxes show the spans of α, β and κ blocks and framework gene blocks, respectively. White, grey, dotted and black boxes show protein‐coding genes, non‐coding RNAs (ncRNAs), small nucleolar RNAs (snoRNAs) and pseudogenes, respectively. Red and blue letters indicate HLA class I / MIC and class II genes, respectively. The location of the α, β and κ blocks containing the cluster of duplicated HLA class I genes and framework gene blocks between them in the class I region are indicated by blue and pink arrows, respectively.

Figure 3

Comparison of genomic structures of the HLA, Mamu‐MHC and H2 regions. Genomic information of the HLA and H2 region was based on the current genome database at the NCBI site, and genomic information of the Mamu‐MHC region was referred from a previous report.25

Figure 4

Comparative genomic map of the protein coding MHC loci among the HLA, Mamu and H2 regions. Orange and blue boxes indicate MHC class I and class II genes, respectively. The classification for protein‐coding genes and pseudogenes is shown in the Supplementary material (Table S3).

Figure 5

Nucleotide sequence‐based phylogenetic tree of MHC class I and class II genes. Multiple sequence alignment was created using the clustalW Sequence Alignment program of the Molecular Evolution Genetics Analysis software 5 (MEGA5: http://www.megasoftware.net/)107 Phylogenetic trees of the MHC genes were constructed by the neighbour‐joining method (MEGA5)108 with a Maximum Composite Likelihood model using exon 4 and exon 3 of the MHC class I and class II genes, respectively. Parentheses and bold letters indicate GenBank/EMBL/DDBJ accession numbers and human MHC genes, respectively.

Figure 6

Gene organization of the most frequent Filipino Mafa‐MHC haplotype. Orange and blue boxes indicate MHC class I and MHC class II genes, respectively.