The repertoire of MHC class I genes in the common marmoset: evidence for functional plasticity

Abstract

In humans, the classical antigen presentation function of major histocompatibility complex (MHC) class I molecules is controlled by the human leukocyte antigen HLA -A, HLA-B and HLA-C loci. A similar observation has been made for great apes and Old World monkey species. In contrast, a New World monkey species such as the cotton-top tamarin (Saguinus oedipus) appears to employ the G locus for its classical antigen presentation function. At present, little is known about the classical MHC class I repertoire of the common marmoset (Callithrix jacchus), another New World monkey that is widely used in biomedical research. In the present population study, no evidence has been found for abundant transcription of classical I class genes. However, in each common marmoset, four to seven different G-like alleles were detected, suggesting that the ancestral locus has been subject to expansion. Segregation studies provided evidence for at least two G-like genes present per haplotype, which are transcribed by a variety of cell types. The alleles of these Caja-G genes cluster in separate lineages, suggesting that the loci diversified considerably after duplication. Phylogenetic analyses of the introns confirm that the Caja-G loci cluster in the vicinity of HLA-G, indicating that both genes shared an ancestor. In contrast to HLA-G, Caja-G shows considerable polymorphism at the peptide-binding sites. This observation, together with the lack of detectable transcripts of A and B-like genes, indicates that Caja-G genes have taken over the function of classical class I genes. These data highlight the extreme plasticity of the MHC class I gene system.

Genomic Sequence Analysis of the MHC Class I G/F Segment in Common Marmoset (Callithrix jacchus)

“…The remaining 562-kb segment (321 kb in contig 1, 141 kb in contig 2, and 100 kb in contig 3), including the duplicated Caja-G/F genes, is represented only by several mini contigs in the WUGSC 3.2 sequence (Table II), which is most likely due to the current quality (draft assembly and not finished sequence) of the common marmoset draft genome sequence. Genomic diversities in the Caja-G loci were suggested to be generated considerably after duplication based on the population study of the Caja-G genes (13). This finding supports that genomic structures of the Caja-G/F segment are different among the Caja-G/F haplotypes.…”

“…From the MHC-B/C segment, which has been under permanent selective pressure in the evolution of primates, a genomic sequence of 1179 kb was determined that includes nine duplicated Caja-B genes (12). In contrast, although four to seven Caja-G-like alleles were detected in each common marmoset from a recent population study (13), the genomic structure of the Caja-G/F segment between GABBR1 and ZNRD1 is still not solved, and 54 alleles of Caja-G and Caja-E are currently listed in the Immuno Polymorphism Database (IPD)-MHC database (14).…”

Gene conversion of the major histocompatibility complex class I Caja‐G in common marmosets (Callithrix jacchus)

“…In our study, 480 sequences of 21 common marmosets were analysed and classified as members of the Caja-G family. Comparison with already confirmed Caja-G sequences [26][27][28] resulted in 34 different alleles in our investigated group of animals. Four of the detected alleles have been published before 26,27 and a total of 30 new alleles, concerning the sequence of exon 1-4, were uploaded to the NCBI database and are presented in Table 1 with GenBank accession numbers, official IPD-MHC nomenclature and number of animals that shared the correspondent alleles.…”

“…Comparison with already confirmed Caja-G sequences [26][27][28] resulted in 34 different alleles in our investigated group of animals. Four of the detected alleles have been published before 26,27 and a total of 30 new alleles, concerning the sequence of exon 1-4, were uploaded to the NCBI database and are presented in Table 1 with GenBank accession numbers, official IPD-MHC nomenclature and number of animals that shared the correspondent alleles. Of 34 MHC class I sequences most alleles were found in one (15) or two (10) marmosets, whereas other alleles like Caja-G*08:23 occurred in 11 different marmosets, that originated from different families (compare Fig.…”

The response of common marmoset immunity against cedar pollen extract

“…Shiina et al determined the gene structure of Caja-G. The Caja-G gene cluster contains 14 loci, at least 5 of which express functional gene products (25); plural alleles have been found in these loci (26)(27)(28)(29). The variation and the binding of peptide suggested that it is more similar to classical HLA in humans, but the real function of Caja-G is yet to be clarified.…”