Antunes S G, de Groot N G, Brok H, Doxiadis G, Menezes A A, Otting N, Bontrop R E
Department of Immunobiology, Biomedical Primate Research Centre, Lange Kleiweg 151, 2288 GJ Rijswijk, The Netherlands.
Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11745-50. doi: 10.1073/pnas.95.20.11745.
The common marmoset (Callithrix jacchus) is a New World primate species that is highly susceptible to fatal infections caused by various strains of bacteria. We present here a first step in the molecular characterization of the common marmoset's Mhc class II genes by nucleotide sequence analysis of the polymorphic exon 2 segments. For this study, genetic material was obtained from animals bred in captivity as well as in the wild. The results demonstrate that the common marmoset has, like other primates, apparently functional Mhc-DR and -DQ regions, but the Mhc-DP region has been inactivated. At the -DR and -DQ loci, only a limited number of lineages were detected. On the basis of the number of alleles found, the -DQA and -B loci appear to be oligomorphic, whereas only a moderate degree of polymorphism was observed for two of three Mhc-DRB loci. The contact residues in the peptide-binding site of the Caja-DRB103 lineage members are highly conserved, whereas the -DRBW16 lineage members show more divergence in that respect. The latter locus encodes five oligomorphic lineages whose members are not observed in any other primate species studied, suggesting rapid evolution, as illustrated by frequent exchange of polymorphic motifs. All common marmosets tested were found to share one monomorphic type of Caja-DRB*W12 allele probably encoded by a separate locus. Common marmosets apparently lack haplotype polymorphism because the number of Caja-DRB loci present per haplotype appears to be constant. Despite this, however, an unexpectedly high number of allelic combinations are observed at the haplotypic level, suggesting that Caja-DRB alleles are exchanged frequently between chromosomes by recombination, promoting an optimal distribution of limited Mhc polymorphisms among individuals of a given population. This peculiar genetic make up, in combination with the limited variability of the major histocompatability complex class II repertoire, may contribute to the common marmoset's susceptibility to particular bacterial infections.
普通狨猴(Callithrix jacchus)是一种新大陆灵长类动物,对多种细菌菌株引起的致命感染高度敏感。我们在此展示了通过对多态性外显子2片段进行核苷酸序列分析,对普通狨猴Mhc II类基因进行分子特征描述的第一步。在本研究中,遗传物质取自圈养和野生的动物。结果表明,普通狨猴与其他灵长类动物一样,具有明显功能性的Mhc-DR和-DQ区域,但Mhc-DP区域已失活。在-DR和-DQ位点,仅检测到有限数量的谱系。基于所发现的等位基因数量,-DQA和-B位点似乎是寡态的,而在三个Mhc-DRB位点中的两个位点仅观察到中等程度的多态性。Caja-DRB103谱系成员的肽结合位点中的接触残基高度保守,而-DRBW16谱系成员在这方面表现出更多差异。后一个位点编码五个寡态谱系,其成员在任何其他研究的灵长类物种中均未观察到,这表明其进化迅速,多态基序的频繁交换就说明了这一点。所有测试的普通狨猴都共享一种可能由单独位点编码的单态性Caja-DRB*W12等位基因类型。普通狨猴显然缺乏单倍型多态性,因为每个单倍型中存在的Caja-DRB位点数量似乎是恒定的。尽管如此,在单倍型水平上仍观察到数量出乎意料的等位基因组合,这表明Caja-DRB等位基因通过重组在染色体之间频繁交换,促进了给定群体个体之间有限的Mhc多态性的最佳分布。这种特殊的基因构成,结合主要组织相容性复合体II类库的有限变异性,可能导致普通狨猴对特定细菌感染易感。