Allelic diversity at the primate Mhc-G locus: Exon 3 bears stop codons in all Cercophitecinae sequences

Allelic diversity at the primate Mhc-G locus: Exon 3 bears stop codons in all Cercophitecinae sequences
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DOI:
10.1007/bf02199801
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发表时间:
1996-01-01
期刊:
影响因子:
3.2
通讯作者:
ArnaizVillena, A
ArnaizVillena, A
中科院分区:
医学4区
文献类型:
--
作者:
Castro, MJ;Morales, P;ArnaizVillena, A

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27个主要组织相容性复合体(Mhc)-G外显子2,外显子3,外显子2和3的等位基因序列一起获得12个不同的内含子2序列。研究了智人、黑猩猩、Panpaniscus、大猩猩、Pongo pygmaeus、Macaca fascicularis、Macaca mulatta和Cercopithecus aethiops个体。多态性不遵循经典的模式,每个域的三个高变区,并发现在所有物种的研究;外显子3(相当于α 2蛋白结构域)显示终止密码子在Cercopithecinae组,但不是在Pongidae和人类组。结果表明,棉顶绢毛猴Mhc-G基因序列与智人和猩猩科亲缘关系较近,而与长尾猴亚科亲缘关系较近,这可能与长尾猴亚科第3外显子存在终止密码子有关。有一个明确的跨物种进化的等位基因在Cercopithecinae,也在外显子2的所有其他类人猿的研究,但一代的等位基因在每个物种内可能存在的外显子3序列。这种差异可能是由于在mRNA剪接水平上,每个物种优先使用外显子2而不是外显子3,以获得适当的功能性G产物。Mhc-G内含子2在所有物种中都存在保守的基序,特别是在161和183位之间的23个碱基对的缺失,这是基因座特异性的,并且在从鱼类和爬行动物到人类的经典I类分子中保守的一些对肽呈递重要的不变残基在Mhc-G等位基因中没有发现;内含子2树状图还显示了每个物种内等位性的特定模式。总之,Mhc-G与其它经典I类基因具有实质性差异:多态性模式、组织分布、基因结构、剪接变异性,以及每个物种内外显子3的等位变异性。G蛋白也可能不同。这表明Mhc-G功能可能不是向克隆型T细胞受体呈递肽。
Twenty-seven major histocompatibility complex (Mhc)-G exon 2, exon 3, and exon 2 and 3 allelic sequences were obtained together with 12 different intron 2 sequences. Homo sapiens, Pan troglodytes, Pan paniscus, Gorilla gorilla, Pongo pygmaeus, Macaca fascicularis, Macaca mulatta, and Cercopithecus aethiops individuals were studied. Polymorphism does not follow the classical pattern of three hypervariable regions per domain and is found in all species studied; exon 3 (equivalent to the alpha 2 protein domain) shows stop codons in the Cercopithecinae group but not in the Pongidae and human groups. Dendrograms show that cotton top tamarin (Saguinus oedipus) Mhc-G sequences are closer to Homo sapiens and Pongidae than to Cercopithecinae, probably due to the stop codons existing at exon 3 of the latter. There is a clear trans-species evolution of allelism in Cercopithecinae and also in exon 2 of all the other apes studied, but a generation of allelism within each species may be present on exon 3 sequences. This discrepancy may be due to the preferential use of exon 2 over exon 3 at the mRNA splicing level within each species in order to obtain the appropriate functional G product. Mhc-G intron 2 shows conserved motifs in all species studied, particularly a 23 base pair deletion between positions 161 and 183 which is locus specific, and some of the invariant residues, important for peptide presentation, conserved in classical class I molecules from fish and reptiles to humans were not found in Mhc-G alleles; the intron 2 dendrogram also shows a particular pattern of allelism within each species, In summary, Mhc-G has substantial differences from other classical class I genes: polymorphism patterns, tissue distribution, gene structure, splicing variability, and probably an allelism variability within each species at exon 3. The G proteins may also be different. This indicates that the Mhc-G function may not be peptide presentation to the clonotypic T-cell receptor.