MHC class I A loci polymorphism and diversity in three Southeast Asian populations of cynomolgus macaque

Cynomolgus macaques (Macaca fascicularis,Mafa) have emerged as important animal models forbiomedical research, necessitating a more extensive characterizationof their major histocompatibility complexpolymorphic regions. The current information on thepolymorphism or diversity of the polygenetic Mafa class IA loci is limited in comparison to the more commonlystudied rhesus macaque Mafa class I A loci. Therefore, inthis paper, to better elucidate the degree and types ofpolymorphisms and genetic differences of Mafa-A1 amongthree native Southeast Asian populations (Indonesian,Vietnamese, and Filipino) and to investigate how the alleledifferences between macaques and humans might haveevolved to affect their respective immune responses, weidentified 83 Mafa-A loci-derived alleles by DNA sequencingof which 66 are newly described. Most alleles areunique to each population, but seven of the most frequentalleles were identical in sequence to some alleles in othermacaque species. We also revealed (1) the large anddynamic genetic and structural differences and similaritiesin allelic variation by analyzing the population allelefrequencies, Hardy-Weinberg’s equilibrium, heterozygosity,nucleotide diversity profiles, and phylogeny, (2) thedifference in genetic structure of populations by Wright’sFST statistic and hierarchical analysis of molecular variance,and (3) the different demographic and selectionpressures on the three populations by performing Tajima’sD test of neutrality. The large level of diversity andpolymorphism at the Mafa-A1 was less evident in theFilipino than in the Vietnam or the Indonesian populations,which may have important implications in animal capture,selection, and breeding for medical research.