Evolutionary stability of MHC class II haplotypes in diverse rhesus macaque populations

Doxiadis

The Journal of Immunology

et al. 2004

Self Cite

In the human population, five major HLA-DRB haplotypes have been identified, whereas the situation in rhesus macaques (Macaca mulatta) is radically different. At least 30 Mamu-DRB region configurations, displaying polymorphism with regard to number and combination of DRB loci present per haplotype, have been characterized. Until now, Mamu-DRB region genes have been studied mainly by genomic sequencing of polymorphic exon 2 segments. However, relatively little is known about the expression status of these genes. To understand which exon 2 segments may represent functional genes, full-length cDNA analyses of -DRA and -DRB were initiated. In the course of the study, 11 cDRA alleles were identified, representing four distinct gene products. Amino acid replacements are confined to the leader peptide and cytoplasmatic tail, whereas residues of the α1 domain involved in peptide binding, are conserved between humans, chimpanzees, and rhesus macaques. Furthermore, from the 11 Mamu-DRB region configurations present in this panel, 28 cDRB alleles were isolated, constituting 12 distinct cDRA/cDRB configurations. Evidence is presented that a single configuration expresses maximally up to three -DRB genes. For some exon 2 DRB sequences, the corresponding transcripts could not be detected, rendering such alleles as probable pseudogenes. The full-length cDRA and cDRB sequences are necessary to construct Mhc class II tetramers, as well as transfectant cell lines. As the rhesus macaque is an important animal model in AIDS vaccine studies, the information provided in this communication is essential to define restriction elements and to monitor immune responses in SIV/simian human immunodeficiency virus-infected rhesus macaques.

Section: Mamu-dr Configurationsmentioning

confidence: 99%

Section: Animals and Cellsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Genetic Makeup of theDRRegion in Rhesus Macaques: Gene Content, Transcripts, and Pseudogenes

Doxiadis

The Journal of Immunology

et al. 2004

Self Cite

“…Investigations by Andrade et al (2004), Doxiadis et al (2003Doxiadis et al ( , 2006, Ferguson et al (2007), Hernandez et al (2007), Smith (1998, 2004), Kanthaswamy et al (2006), Malhi et al (2007), Morin et al (1997), Penedo et al (2005), Satkoski et al (2007), and Viray et al (2001) have all characterized the genetic composition of rhesus macaque populations in the wild and in captivity. Most of these studies have reported discrete genetic differences between Indian and Chinese rhesus macaques and much greater genetic heterogeneity and substructuring in the latter than in the former.…”

Section: Introductionmentioning

confidence: 99%

Hybridization and Stratification of Nuclear Genetic Variation in Macaca mulatta and M. fascicularis

et al. 2008

Genotypes for 13 short tandem repeats (STRs) were used to assess the genetic diversity within and differentiation among populations of rhesus macaques (Macaca mulatta) from mainland Asia and long-tailed macaques (M. fascicularis) from mainland and insular Southeast Asia. These animals were either recently captured in the wild or derived from wild-caught founders maintained in captivity for biomedical research.A large number of alleles is shared between the two macaque species but a significant genetic division between them persists. This distinction is more clear-cut among populations that are not, or are unlikely to have recently been, geographically contiguous. Our results suggest there has been significant interspecies nuclear gene flow between rhesus macaques and long-tailed macaques on the mainland. Comparisons of mainland and island populations of long-tailed macaques reflect marked genetic subdivisions due to barriers to migration. Geographic isolation has restricted gene flow, allowing island populations to become subdivided and genetically differentiated. Indonesian long-tailed macaques show evidence of long-term separation and genetic isolation from the mainland populations, while long-tailed macaques from the Philippines and Mauritius both display evidence of founder effects and subsequent isolation, with the impact from genetic drift being more profound in the latter.

Proc. Natl. Acad. Sci. U.S.A.

“…For example, within rhesus macaques Ͼ30 different DRB region configurations have been defined, whereas in humans only 5 have been documented (15)(16)(17). Common marmosets, mostly born as nonidentical twins, are natural bone-marrow chimeras because of a sharing of blood circulation through placental fusion during gestation.…”

mentioning

confidence: 99%

Reactivation by exon shuffling of a conservedHLA-DR3-like pseudogene segment in a New World primate species

Doxiadis¹,

Wiel²,

Brok

et al. 2006

Self Cite

The common marmoset (Callithrix jacchus), a New World monkey species with a limited MHC class II repertoire, is highly susceptible to certain bacterial infections. Genomic analysis of exon 2 sequences documented the existence of only one DRB region configuration harboring three loci. Two of these loci display moderate levels of allelic polymorphism, whereas the -DRB*W12 gene appears to be monomorphic. This study shows that only the Caja-DRB*W16 and -DRB*W12 loci produce functional transcripts. The Caja-DRB1*03 locus is occupied by a pseudogene, given that most of the transcripts, if detected at all, show imperfections and are present at low levels. Moreover, two hybrid transcripts were identified that feature the evolutionarily conserved peptidebinding motif characteristic for the Caja-DRB1*03 gene. Thus, the severely reduced MHC class II repertoire in common marmosets has been expanded by reactivation of a pseudogene segment as a result of exon shuffling.MHC ͉ non-human primates ͉ selection ͉ immune response ͉ evolution