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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. [ABSTRACT FROM AUTHOR]

The authors regret that an error was present in the Fig. 5 of the above article; some digits in the DRB allele-designations in Fig. 5 have been lost, and are incorrectly presented by only two digits. The correct allele-designations should have been four (or six) digits. The correct Figure is now presented correctly. [ABSTRACT FROM AUTHOR]

Background: The major histocompatibility complex (MHC) is a key model of genetic polymorphism. Selection pressure by pathogens or other microevolutionary forces may result in a high rate of non-synonymous substitutions at the codons specifying the contact residues of the antigen binding sites (ABS), and the maintenance of extreme MHC allelic variation at the population/species level. Therefore, selection forces favouring MHC variability for any reason should cause a correlated evolution between substitution rates and allelic polymorphism. To investigate this prediction, we characterised nucleotide substitution rates and allelic polymorphism (i.e. the number of alleles detected in relation to the number of animals screened) of several Mhc class II DRB lineages in 46 primate species, and tested for a correlation between them. Results: First, we demonstrate that species-specific and lineage-specific evolutionary constraints favour species- and lineage-dependent substitution rate at the codons specifying the ABS contact residues (i.e. certain species and lineages can be characterised by high substitution rate, while others have low rate). Second, we show that although the degree of the non-synonymous substitution rate at the ABS contact residues was systematically higher than the degree of the synonymous substitution rate, these estimates were strongly correlated when we controlled for species-specific and lineage-specific effects, and also for the fact that different studies relied on different sample size. Such relationships between substitution rates of different types could even be extended to the non-contact residues of the molecule. Third, we provide statistical evidence that increased substitution rate along a MHC gene may lead to allelic variation, as a high substitution rate can be observed in those lineages in which many alleles are maintained. Fourth, we show that the detected patterns were independent of phylogenetic constraints. When we used phylogenetic models that control for similarity between species, due to common descent, and focused on variations within a single lineage (DRB1*03), the positive relationship between different substitution rates and allelic polymorphisms was still robust. Finally, we found the same effects to emerge in the analyses that eliminated within-species variation in MHC traits by using strictly single population-level studies. However, in a set of contrasting analyses, in which we focused on the non-functional DRB6 locus, the correlation between substitution rates and allelic variation was not prevalent. Conclusion: Our results indicate that positive selection for the generation of allelic polymorphism acting on the functional part of the protein has consequences for the nucleotide substitution rate along the whole exon 2 sequence of the Mhc-DRB gene. Additionally, we proved that an increased substitution rate can promote allelic variation within lineages. Consequently, the evolution of different characteristics of genetic polymorphism is not independent. [ABSTRACT FROM AUTHOR]

Abstract: In most primate species, the class II region of the Major Histocompatibility Complex (MHC) displays diversity with regard to gene copy number and combination of DRB genes present per region configuration. Some of these loci exhibit extremely high levels of allelic variability, whereas others display only moderate levels of polymorphism. To understand the evolutionary history of the various HLA-DR region genes, a large number of full-length sequences of rhesus macaques, chimpanzees and humans were determined. The exon–intron organisation of the DRA gene, displaying only low levels of polymorphism, appears to have been highly conserved during primate evolution. The physical length of various DRB genes/alleles, however, fluctuates significantly in primates due to the presence of indels (insertions/deletions), mainly mapping to intron 1. Phylogenetic evidence supports the notion that the generation of new DRB genes is a dynamic and steadily ongoing process. Indeed, most of the primate DRB alleles investigated represent relatively young entities, possessing species-unique sequences. This seems to contradict the current view that the highly similar peptide binding motifs of many HLA-, Patr- and Mamu-DR molecules, encoded by exon 2 of the DRB gene, represent old entities, which predate primate speciation. As no evidence was found for convergent evolution, the combination of these two observations indicates that ancient peptide binding motifs are frequently reshuffled among duplicated members of the HLA-DRB multigene family. [Copyright &y& Elsevier]

A thoroughly characterized breeding colony of 172 pedigreed rhesus macaques was used to analyze exon 2 of the polymorphic Mamu-DPB1, -DQA1, -DQB1, and -DRB loci. Most of the monkeys or their ancestors originated in India, though the panel also included animals from Burma and China, as well as some of unknown origin and mixed breeds. In these animals, mtDNA appears to correlate with the aforementioned geographic origin, and a large number of Mamu class II alleles were observed. The different Mamu-DPB1 alleles were largely shared between monkeys of different origin, whereas in humans particular alleles appear to be unique for ethnic populations. In contrast to Mamu-DPB1, the highly polymorphic -DQA1/DQB1 alleles form tightly linked pairs that appear to be about two-thirds population specific. For most of the DQA1/DQB1 pairs, Mamu-DRB region configurations present on the same chromosome have been ascertained, resulting in 41 different -DQ/DRB haplotypes. These distinct DQ/DRB haplotypes seem to be specific for monkeys of a determined origin. Thus, in evolutionary terms, the Mamu-DP, -DQ, and -DR regions show increasing instability with regard to allelic polymorphism, such as for -DP/DQ, or gene content and allelic polymorphism, such as for -DR, resulting in population-specific class II haplotypes. Furthermore, novel haplotypes are generated by recombination-like events. The results imply that mtDNA analysis in combination with Mhc typing is a helpful tool for selecting animals for biomedical experiments. [ABSTRACT FROM AUTHOR]

In the past decade, the major histocompatibility complex (MHC) class II region of several primate species has been investigated extensively. Here we will discuss the similarities and differences found in the MHC class II repertoires of primate species including humans, chimpanzees, rhesus macaques, cotton-top tamarins and common marmosets. Such types of comparisons shed light on the evolutionary stability of MHC class II alleles, lineages and loci as well as on the evolutionary origin and biological significance of haplotype configurations. [ABSTRACT FROM AUTHOR]