Dynamic evolution of Mhc haplotypes in cynomolgus macaques of different geographic origins

Abstract

The major histocompatibility complex (MHC) plays a key role in immune defense, and the Mhc genes of cynomolgus macaque display a high degree of polymorphism. Based on their geographic distribution, different populations of cynomolgus macaques are recognized. Here we present the characterization of the Mhc class I and II repertoire of a large pedigreed group of cynomolgus macaques originating from the mainland north of the isthmus of Kra ( N = 42). Segregation analyses resulted in the definition of 81 unreported Mafa-A/B/DRB/DQ/DP haplotypes, which include 32 previously unknown DRB regions. In addition, we report 13 newly defined Mafa-A/B/DRB/DQ/DP haplotypes in a group of cynomolgus macaques originating from the mainland south of the isthmus of Kra/Maritime Southeast Asia ( N = 16). A relatively high level of sharing of Mafa-A (51%) and Mafa-B (40%) lineage groups is observed between the populations native to the north and the south of isthmus of Kra. At the allelic level, however, the Mafa-A/B haplotypes seem to be characteristic of a population. An overall comparison of all currently known data revealed that each geographic population has its own specific combinations of Mhc class I and II haplotypes. This illustrates the dynamic evolution of the cynomolgus macaque Mh c region, which was most likely generated by recombination and maintained by selection due to the differential pathogenic pressures encountered in different geographic areas. Supplementary Information The online version contains supplementary material available at 10.1007/s00251-021-01249-y.

Complete sequencing of a cynomolgus macaque major histocompatibility complex haplotype

“…There is no reason to believe that the Indonesian cynomolgus macaque sequenced for the Macaca_ fascicularis_5.0 assembly would not have a similar MHC class I gene density as the cy0333 M3 haplotype of MCM. Mauritian cynomolgus macaques are most likely derived from a small population of Indonesian cynomolgus macaques, and previous MHC haplotyping studies of cynomolgus macaques from Indonesia as well as other geographic origins have shown expected levels of segmental duplications for these regions (Shortreed et al 2020; de Groot et al 2022). However, the MHC class I A and class I B regions for Macaca_fascicularis_5.0 are both significantly shorter than their cy0333 counterparts.…”

“…The full genomic MHC region of Macaca_fascicularis_5.0 is also notably over 1.3 Mb shorter than macaques from Indonesia as well as other geographic origins have shown expected levels of segmental duplications for these regions (Shortreed et al 2020;de Groot et al 2022). However, the MHC class I A and class I B regions for Macaca_fascicularis_5.0 are both significantly shorter than their cy0333 counterparts.…”

Long-read assembly of major histocompatibility complex and killer cell immunoglobulin-like receptor genome regions in cynomolgus macaque

“…One to two major transcribed and up to five minor transcribed Mafa-A genes may be detected per haplotype [ 93 – 97 ]. A haplotype can comprise one to seven major transcribed and up to fifteen minor transcribed Mafa-B genes [ 93 – 97 ]. Our data illustrated that the number of Mafa-A and Mafa-B genes varies among haplotypes in this assembled cynomolgus macaque genome.…”

“…Mamu-B*017:01 controls SIV replication and disease progression [ 26 ]. The B1, B4, and B9 genes were reported to have low transcription levels [ 93 – 97 ], and only three alleles ( Mafa-B*180:02:01:02nov, Mafa-B*124:03:01:01nov, Mafa-B*021:07nov ) were detected in the B9 locus. The combinations I*01-B*056:05-B*034:04 (animal 1, 5, 6, 18, 21) and I*01-B*034:04-B11L*01 (animal 16) matched the Mafa-B region in contig utg000348l.…”

“…The number of Mafa-A and Mafa-B genes varies from one to six and one to seventeen per haplotype, respectively [93][94][95][96]. One to two major transcribed and up to five minor transcribed Mafa-A genes may be detected per haplotype [93][94][95][96][97]. A haplotype can comprise one to seven major transcribed and up to fifteen minor transcribed Mafa-B genes [93][94][95][96][97].…”