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Major histocompatibility complex (Mhc) class Ib gene duplications, organization and expression patterns in mouse strain C57BL/6.

ABSTRACT: BACKGROUND: The mouse has more than 30 Major histocompatibility complex (Mhc) class Ib genes, most of which exist in the H2 region of chromosome 17 in distinct gene clusters. Although recent progress in Mhc research has revealed the unique roles of several Mhc class Ib genes in the immune and non-immune systems, the functions of many class Ib genes have still to be elucidated. To better understand the roles of class Ib molecules, we have characterized their gene duplication, organization and expression patterns within the H2 region of the mouse strain C57BL/6. RESULTS: The genomic organization of the H2-Q, -T and -M regions was analyzed and 21 transcribed Mhc class Ib genes were identified within these regions. Dot-plot and phylogenetic analyses implied that the genes were generated by monogenic and/or multigenic duplicated events. To investigate the adult tissue, embryonic and placental expressions of these genes, we performed RT-PCR gene expression profiling using gene-specific primers. Both tissue-wide and tissue-specific gene expression patterns were obtained that suggest that the variations in the gene expression may depend on the genomic location of the duplicated genes as well as locus specific mechanisms. The genes located in the H2-T region at the centromeric end of the cluster were expressed more widely than those at the telomeric end, which showed tissue-restricted expression in spite of nucleotide sequence similarities among gene paralogs. CONCLUSION: Duplicated Mhc class Ib genes located in the H2-Q, -T and -M regions are differentially expressed in a variety of developing and adult tissues. Our findings form the basis for further functional validation studies of the Mhc class Ib gene expression profiles in specific tissues, such as the brain. The duplicated gene expression results in combination with the genome analysis suggest the possibility of long-range regulation of H2-T gene expression and/or important, but as yet unidentified nucleotide changes in the promoter or enhancer regions of the genes. Since the Mhc genomic region has diversified among mouse strains, it should be a useful model region for comparative analyses of the relationships between duplicated gene organization, evolution and the regulation of expression patterns.

SUBMITTER: Ohtsuka M

PROVIDER: S-EPMC2375909 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Major histocompatibility complex (Mhc) class Ib gene duplications, organization and expression patterns in mouse strain C57BL/6.

Ohtsuka Masato M Inoko Hidetoshi H Kulski Jerzy K JK Yoshimura Shinichi S

BMC genomics 20080417

<h4>Background</h4>The mouse has more than 30 Major histocompatibility complex (Mhc) class Ib genes, most of which exist in the H2 region of chromosome 17 in distinct gene clusters. Although recent progress in Mhc research has revealed the unique roles of several Mhc class Ib genes in the immune and non-immune systems, the functions of many class Ib genes have still to be elucidated. To better understand the roles of class Ib molecules, we have characterized their gene duplication, organization ...[more]

PMID: 18416856

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Project description:Sirenians share with cetaceans and pinnipeds several convergent traits selected for the aquatic lifestyle. Living in water poses new challenges not only for locomotion and feeding but also for combating new pathogens, which may render the immune system one of the best tools aquatic mammals have for dealing with aquatic microbial threats. So far, only cetaceans have had their class II Major Histocompatibility Complex (MHC) organization characterized, despite the importance of MHC genes for adaptive immune responses. This study aims to characterize the organization of the marine mammal class II MHC using publicly available genomes. We located class II sequences in the genomes of one sirenian, four pinnipeds and eight cetaceans using NCBI-BLAST and reannotated the sequences using local BLAST search with exon and intron libraries. Scaffolds containing class II sequences were compared using dotplot analysis and introns were used for phylogenetic analysis. The manatee class II region shares overall synteny with other mammals, however most DR loci were translocated from the canonical location, past the extended class II region. Detailed analysis of the genomes of closely related taxa revealed that this presumed translocation is shared with all other living afrotherians. Other presumptive chromosome rearrangements in Afrotheria are the deletion of DQ loci in Afrosoricida and deletion of DP in E. telfairi. Pinnipeds share the main features of dog MHC: lack of a functional pair of DPA/DPB genes and inverted DRB locus between DQ and DO subregions. All cetaceans share the Cetartiodactyla inversion separating class II genes into two subregions: class IIa, with DR and DQ genes, and class IIb, with non-classic genes and a DRB pseudogene. These results point to three distinct and unheralded class II MHC structures in marine mammals: one canonical organization but lacking DP genes in pinnipeds; one bearing an inversion separating IIa and IIb subregions lacking DP genes found in cetaceans; and one with a translocation separating the most diverse class II gene from the MHC found in afrotherians and presumptive functional DR, DQ, and DP genes. Future functional research will reveal how these aquatic mammals cope with pathogen pressures with these divergent MHC organizations.

Project description:BackgroundWe have previously identified associations between major histocompatibility complex (MHC) class I and resistance towards bacterial and viral pathogens in Atlantic salmon. To evaluate if only MHC or also closely linked genes contributed to the observed resistance we ventured into sequencing of the duplicated MHC class I regions of Atlantic salmon.ResultsNine BACs covering more than 500 kb of the two duplicated MHC class I regions of Atlantic salmon were sequenced and the gene organizations characterized. Both regions contained the proteasome components PSMB8, PSMB9, PSMB9-like and PSMB10 in addition to the transporter for antigen processing TAP2, as well as genes for KIFC1, ZBTB22, DAXX, TAPBP, BRD2, COL11A2, RXRB and SLC39A7. The IA region contained the recently reported MHC class I Sasa-ULA locus residing approximately 50 kb upstream of the major Sasa-UBA locus. The duplicated class IB region contained an MHC class I locus resembling the rainbow trout UCA locus, but although transcribed it was a pseudogene. No other MHC class I-like genes were detected in the two duplicated regions. Two allelic BACs spanning the UBA locus had 99.2% identity over 125 kb, while the IA region showed 82.5% identity over 136 kb to the IB region. The Atlantic salmon IB region had an insert of 220 kb in comparison to the IA region containing three chitin synthase genes.ConclusionWe have characterized the gene organization of more than 500 kb of the two duplicated MHC class I regions in Atlantic salmon. Although Atlantic salmon and rainbow trout are closely related, the gene organization of their IB region has undergone extensive gene rearrangements. The Atlantic salmon has only one class I UCA pseudogene in the IB region while trout contains the four MHC UCA, UDA, UEA and UFA class I loci. The large differences in gene content and most likely function of the salmon and trout class IB region clearly argues that sequencing of salmon will not necessarily provide information relevant for trout and vice versa.

Dataset Information

Major histocompatibility complex (Mhc) class Ib gene duplications, organization and expression patterns in mouse strain C57BL/6.

Publications

Major histocompatibility complex (Mhc) class Ib gene duplications, organization and expression patterns in mouse strain C57BL/6.

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