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Structure of miniature swine class II DRB genes: conservation of hypervariable amino acid residues between distantly related mammalian species.

ABSTRACT: As part of our studies of the class II genes of miniature swine, we have isolated and characterized cDNA clones corresponding to DRB genes from two major histocompatibility complex homozygous strains. Comparison of the sequences of these clones to those of human DRB genes revealed a striking amino acid homology between the hypervariable residues of SLA-DRBc and the human DRB1-0101 allele. The percentage of differences in these residues between the pig DRBc allele and the human DRB1-0101 allele was significantly lower (29%) than that between the DRB1-0101 allele and all other human alleles (average, 66.2%). This similarity was not seen in a comparison of the number of silent substitutions, by which the swine DRBc and the human DRB-0101 differed. Since phenotypic selection operates at the level of protein products rather than nucleotide sequences, these data suggest the existence of selective mechanisms that have resulted in similar hypervariable regions in certain alleles even in these widely disparate species. Consistent with this hypothesis, an examination of available murine and bovine class II sequences revealed a homology in hypervariable residues between the human DRB1-1401 allele and the mouse E beta s allele as well as a cow DRB allele. Consideration of these data along with intraspecies allelic sequence comparisons suggests that at least some of the interspecies similarities have emerged as the result of convergent evolution, possibly as the result of a need to react to common pathogens.

SUBMITTER: Gustafsson K

PROVIDER: S-EPMC55261 | biostudies-other | 1990 Dec

REPOSITORIES: biostudies-other

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Structure of miniature swine class II DRB genes: conservation of hypervariable amino acid residues between distantly related mammalian species.

Gustafsson K K Germana S S Hirsch F F Pratt K K LeGuern C C Sachs D H DH

Proceedings of the National Academy of Sciences of the United States of America 19901201 24

As part of our studies of the class II genes of miniature swine, we have isolated and characterized cDNA clones corresponding to DRB genes from two major histocompatibility complex homozygous strains. Comparison of the sequences of these clones to those of human DRB genes revealed a striking amino acid homology between the hypervariable residues of SLA-DRBc and the human DRB1-0101 allele. The percentage of differences in these residues between the pig DRBc allele and the human DRB1-0101 allele w ...[more]

PMID: 2124703

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Project description:BackgroundAlthough bats are natural reservoirs of many pathogens, few studies have been conducted on the genetic variation and detection of selection in major histocompatibility complex (MHC) genes. These genes are critical for resistance and susceptibility to diseases, and host-pathogen interactions are major determinants of their extensive polymorphism. Here we examined spatial patterns of diversity of the expressed MHC class II DRB gene of three sympatric Neotropical bats, Carollia perspicillata and Desmodus rotundus (Phyllostomidae), and Molossus molossus (Molossidae), all of which use the same environments (e.g., forests, edge habitats, urban areas). Comparison with neutral marker (mtDNA D-loop) diversity was performed at the same time.ResultsTwenty-three DRB alleles were identified in 19 C. perspicillata, 30 alleles in 35 D. rotundus and 20 alleles in 28 M. molossus. The occurrence of multiple DRB loci was found for the two Phyllostomidae species. The DRB polymorphism was high in all sampling sites and different signatures of positive selection were detected depending on the environment. The patterns of DRB diversity were similar to those of neutral markers for C. perspicillata and M. molossus. In contrast, these patterns were different for D. rotundus for which a geographical structure was highlighted. A heterozygote advantage was also identified for this species. No recombination or gene conversion event was found and phylogenetic relationships showed a trans-species mode of evolution in the Phyllostomids.ConclusionsThis study of MHC diversity demonstrated the strength of the environment and contrasting pathogen pressures in shaping DRB diversity. Differences between positively selected sites identified in bat species highlighted the potential role of gut microbiota in shaping immune responses. Furthermore, multiple geographic origins and/or population admixtures observed in C. perspicillata and M. molossus populations acted as an additional force in shaping DRB diversity. In contrast, DRB diversity of D. rotundus was shaped by environment rather than demographic history.

Dataset Information

Structure of miniature swine class II DRB genes: conservation of hypervariable amino acid residues between distantly related mammalian species.

Publications

Structure of miniature swine class II DRB genes: conservation of hypervariable amino acid residues between distantly related mammalian species.

Similar Datasets

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