Dataset Information

Transspecies dimorphic allelic lineages of the proteasome subunit beta-type 8 gene (PSMB8) in the teleost genus Oryzias.

ABSTRACT: The proteasome subunit ?-type 8 (PSMB8) gene in the jawed vertebrate MHC genomic region encodes a catalytic subunit of the immunoproteasome involved in the generation of peptides to be presented by the MHC class I molecules. A teleost, the medaka (Oryzias latipes), has highly diverged dimorphic allelic lineages of the PSMB8 gene with only about 80% amino acid identity, termed "PSMB8d" and "PSMB8N," which have been retained by most wild populations analyzed. To elucidate the evolutionary origin of these two allelic lineages, seven species of the genus Oryzias were analyzed for their PSMB8 allelic sequences using a large number of individuals from wild populations. All the PSMB8 alleles of these species were classified into one of these two allelic lineages based on their nucleotide sequences of exons and introns, indicating that the Oryzias PSMB8 gene has a truly dichotomous allelic lineage. Retention of both allelic lineages was confirmed except for one species. The PSMB8d lineage showed a higher frequency than the PSMB8N lineage in all seven species. The two allelic lineages showed curious substitutions at the 31st and 53rd residues of the mature peptide, probably involved in formation of the S1 pocket, suggesting that these allelic lineages show a functional difference in cleavage specificity. These results indicate that the PSMB8 dimorphism was established before speciation within the genus Oryzias and has been maintained for more than 30-60 million years under a strict and asymmetric balancing selection through several speciation events.

SUBMITTER: Miura F

PROVIDER: S-EPMC3003058 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Transspecies dimorphic allelic lineages of the proteasome subunit beta-type 8 gene (PSMB8) in the teleost genus Oryzias.

Miura Fumi F Tsukamoto Kentaro K Mehta Ratnesh Bhai RB Naruse Kiyoshi K Magtoon Wichian W Nonaka Masaru M

Proceedings of the National Academy of Sciences of the United States of America 20101123 50

The proteasome subunit β-type 8 (PSMB8) gene in the jawed vertebrate MHC genomic region encodes a catalytic subunit of the immunoproteasome involved in the generation of peptides to be presented by the MHC class I molecules. A teleost, the medaka (Oryzias latipes), has highly diverged dimorphic allelic lineages of the PSMB8 gene with only about 80% amino acid identity, termed "PSMB8d" and "PSMB8N," which have been retained by most wild populations analyzed. To elucidate the evolutionary origin o ...[more]

PMID: 21098669

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Project description:Autoimmunity has been implicated in the destruction of melanocytes from vitiligo skin. Major histocompatibility complex (MHC) class-II linked genes proteasome subunit beta 8 (PSMB8) and transporter associated with antigen processing 1 (TAP1), involved in antigen processing and presentation have been reported to be associated with several autoimmune diseases including vitiligo.To explore PSMB8 rs2071464 and TAP1 rs1135216 single nucleotide polymorphisms and to estimate the expression of PSMB8 and TAP1 in patients with vitiligo and unaffected controls from Gujarat.PSMB8 rs2071464 polymorphism was genotyped using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) and TAP1 rs1135216 polymorphism was genotyped by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in 378 patients with vitiligo and 509 controls. Transcript levels of PSMB8 and TAP1 were measured in the PBMCs of 91 patients and 96 controls by using qPCR. Protein levels of PSMB8 were also determined by Western blot analysis.The frequency of 'TT' genotype of PSMB8 polymorphism was significantly lowered in patients with generalized and active vitiligo (p = 0.019 and p = 0.005) as compared to controls suggesting its association with the activity of the disease. However, TAP1 polymorphism was not associated with vitiligo susceptibility. A significant decrease in expression of PSMB8 at both transcript level (p = 0.002) as well as protein level (p = 0.0460) was observed in vitiligo patients as compared to controls. No significant difference was observed between patients and controls for TAP1 transcripts (p = 0.553). Interestingly, individuals with the susceptible CC genotype of PSMB8 polymorphism showed significantly reduced PSMB8 transcript level as compared to that of CT and TT genotypes (p = 0.009 and p = 0.003 respectively).PSMB8 rs2071464 was associated with generalized and active vitiligo from Gujarat whereas TAP1 rs1135216 showed no association. The down-regulation of PSMB8 in patients with risk genotype 'CC' advocates the vital role of PSMB8 in the autoimmune basis of vitiligo.

Dataset Information

Transspecies dimorphic allelic lineages of the proteasome subunit beta-type 8 gene (PSMB8) in the teleost genus Oryzias.

Publications

Transspecies dimorphic allelic lineages of the proteasome subunit beta-type 8 gene (PSMB8) in the teleost genus Oryzias.

Similar Datasets

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