Gyllensten U B, Lashkari D, Erlich H A
Department of Medical Genetics, University of Uppsala, Sweden.
Proc Natl Acad Sci U S A. 1990 Mar;87(5):1835-9. doi: 10.1073/pnas.87.5.1835.
The allelic diversity at HLA class II loci either arose after the divergence of hominoid lineages or, alternatively, the polymorphism was present before speciation and has been maintained by selection. Here, we report the use of oligonucleotide primers to amplify, by the polymerase chain reaction, and sequence the polymorphic second exon of the DQB locus from 11 species, spanning more than 40 million years of mammalian evolution. Phylogenetic analysis reveals that of the four human DQB allelic types (DQB1-B4), three (DQB1-3) were found in chimpanzee and gorilla and two (DQB3 and -4) were identified in the rhesus monkey, suggesting that some of these types are 5-20 million years old. The ratio of replacement to silent substitutions was calculated between members of the same allelic type from different species. These results suggest that the evolution of the DQB3 allelic type is more constrained than that of the DQB1 allelic type; both evolve more slowly than the DXB locus, a linked but presumably nonexpressed locus. Further, the clustering of allelic subtypes by species in the phylogenetic tree indicates that allelic diversification has occurred subsequent to the divergence of hominoids. Finally, some haplotype combinations of DQA and DQB alleles are common to several hominoid species and may have been maintained for at least 5 million years.
HLA II类基因座的等位基因多样性要么是在类人猿谱系分化之后产生的，要么是在物种形成之前就存在多态性，并通过选择得以维持。在此，我们报告了使用寡核苷酸引物通过聚合酶链反应扩增并测序11个物种DQB基因座的多态性第二外显子，这些物种跨越了超过4000万年的哺乳动物进化历程。系统发育分析表明，人类的四种DQB等位基因类型（DQB1 - B4）中，有三种（DQB1 - 3）在黑猩猩和大猩猩中被发现，两种（DQB3和 - 4）在恒河猴中被鉴定出来，这表明其中一些类型已有500万至2000万年的历史。计算了来自不同物种的相同等位基因类型成员之间的替换与沉默替换的比率。这些结果表明，DQB3等位基因类型的进化比DQB1等位基因类型受到的限制更多；两者的进化都比DXB基因座慢，DXB基因座是一个连锁但可能不表达的基因座。此外，系统发育树中按物种聚类的等位基因亚型表明，等位基因多样化是在类人猿分化之后发生的。最后，DQA和DQB等位基因的一些单倍型组合在几个类人猿物种中是常见的，并且可能已经维持了至少500万年。
