Dataset Information

The chimpanzee Mhc-DRB region revisited: gene content, polymorphism, pseudogenes, and transcripts.

ABSTRACT: In humans, great apes, and different monkey species, the major histocompatibility complex (MHC) class II DRB region is known to display considerable copy number variation. The microsatellite D6S2878 has been shown to be a valuable marker for haplotyping the DR region in humans and macaque species. The present report illustrates that chimpanzee haplotypes also can be discriminated with this marker. The analyses resulted in the description of nine different region configurations, of which seven are present within the West African chimpanzee population studied. The region configurations vary in gene content from two up to five DRB genes. Subsequent cDNA sequencing increased the number of known full-length Patr-DRB sequences from 3 to 32, and shows that one to three Patr-DRB genes per haplotype apparently produce functional transcripts. This is more or less comparable to humans and rhesus macaques. Moreover, microsatellite analysis in concert with full-length DRB gene sequencing showed that the Patr-DRB*W9 and -DRB3*01/02 lineages most likely arose from a common ancestral lineage: hence, the Patr-DRB*W9 lineage was renamed to Patr-DRB3*07. Overall, the data demonstrate that the D6S2878 microsatellite marker allows fast and accurate haplotyping of the Patr-DRB region. In addition, the limited amount of allelic variation observed at the various Patr-DRB genes is in agreement with the fact that chimpanzees experienced a selective sweep that may have been caused by an ancient retroviral infection.

SUBMITTER: de Groot NG

PROVIDER: S-EPMC2788069 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The chimpanzee Mhc-DRB region revisited: gene content, polymorphism, pseudogenes, and transcripts.

de Groot Natasja G NG Heijmans Corrine M C CM de Groot Nanine N Doxiadis Gaby G M GG Otting Nel N Bontrop Ronald E RE

Molecular immunology 20091002 2-3

In humans, great apes, and different monkey species, the major histocompatibility complex (MHC) class II DRB region is known to display considerable copy number variation. The microsatellite D6S2878 has been shown to be a valuable marker for haplotyping the DR region in humans and macaque species. The present report illustrates that chimpanzee haplotypes also can be discriminated with this marker. The analyses resulted in the description of nine different region configurations, of which seven ar ...[more]

PMID: 19800692

Similar Datasets

Project description:Differences in host susceptibility to different parasite types are largely based on the degree of matching between immune genes and parasite antigens. Specifically the variable genes of the major histocompatibility complex (MHC) play a major role in the defence of parasites. However, underlying genetic mechanisms in wild populations are still not well understood because there is a lack of studies which deal with multiple parasite infections and their competition within. To gain insights into these complex associations, we implemented the full record of gastrointestinal nematodes from 439 genotyped individuals of the striped mouse, Rhabdomys pumilio. We used two different multivariate approaches to test for associations between MHC class II DRB genotype and multiple nematodes with regard to the main pathogen-driven selection hypotheses maintaining MHC diversity and parasite species-specific co-evolutionary effects. The former includes investigations of a 'heterozygote advantage', or its specific form a 'divergent-allele advantage' caused by highly dissimilar alleles as well as possible effects of specific MHC-alleles selected by a 'rare allele advantage' (= negative 'frequency-dependent selection'). A combination of generalized linear mixed models (GLMMs) and co-inertia (COIA) analyses made it possible to consider multiple parasite species despite the risk of type I errors on the population and on the individual level. We could not find any evidence for a 'heterozygote' advantage but support for 'divergent-allele' advantage and infection intensity. In addition, both approaches demonstrated high concordance of positive as well as negative associations between specific MHC alleles and certain parasite species. Furthermore, certain MHC alleles were associated with more than one parasite species, suggesting a many-to-many gene-parasite co-evolution. The most frequent allele Rhpu-DRB*38 revealed a pleiotropic effect, involving three nematode species. Our study demonstrates the co-existence of specialist and generalist MHC alleles in terms of parasite detection which may be an important feature in the maintenance of MHC polymorphism.

Project description:BackgroundThe 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.ResultsFirst, 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.ConclusionOur 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.

Dataset Information

The chimpanzee Mhc-DRB region revisited: gene content, polymorphism, pseudogenes, and transcripts.

Publications

The chimpanzee Mhc-DRB region revisited: gene content, polymorphism, pseudogenes, and transcripts.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets