Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan.
Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21599-604. doi: 10.1073/pnas.1012881107. Epub 2010 Nov 23.
The proteasome subunit β-type 8 (PSMB8) gene in the jawed vertebrate MHC genomic region encodes a catalytic subunit of the immunoproteasome involved in the generation of peptides to be presented by the MHC class I molecules. A teleost, the medaka (Oryzias latipes), has highly diverged dimorphic allelic lineages of the PSMB8 gene with only about 80% amino acid identity, termed "PSMB8d" and "PSMB8N," which have been retained by most wild populations analyzed. To elucidate the evolutionary origin of these two allelic lineages, seven species of the genus Oryzias were analyzed for their PSMB8 allelic sequences using a large number of individuals from wild populations. All the PSMB8 alleles of these species were classified into one of these two allelic lineages based on their nucleotide sequences of exons and introns, indicating that the Oryzias PSMB8 gene has a truly dichotomous allelic lineage. Retention of both allelic lineages was confirmed except for one species. The PSMB8d lineage showed a higher frequency than the PSMB8N lineage in all seven species. The two allelic lineages showed curious substitutions at the 31st and 53rd residues of the mature peptide, probably involved in formation of the S1 pocket, suggesting that these allelic lineages show a functional difference in cleavage specificity. These results indicate that the PSMB8 dimorphism was established before speciation within the genus Oryzias and has been maintained for more than 30-60 million years under a strict and asymmetric balancing selection through several speciation events.
脊椎动物 MHC 基因组区域中的蛋白酶体亚基β型 8 (PSMB8) 基因编码免疫蛋白酶体的催化亚基,该酶参与生成要由 MHC Ⅰ类分子呈递的肽。一种硬骨鱼,即青鳉(Oryzias latipes),具有高度分化的 PSMB8 基因二态等位基因系,其氨基酸同一性约为 80%,称为“PSMB8d”和“PSMB8N”,大多数分析的野生种群都保留了这两种等位基因系。为了阐明这两种等位基因系的进化起源,使用来自野生种群的大量个体对七个 Oryzias 属物种的 PSMB8 等位基因序列进行了分析。根据外显子和内含子的核苷酸序列,这些物种的所有 PSMB8 等位基因都分为这两种等位基因系之一,表明 Oryzias PSMB8 基因具有真正的二分等位基因系。除了一个物种外,保留了这两种等位基因系。在所有七个物种中,PSMB8d 谱系的频率均高于 PSMB8N 谱系。这两个等位基因系在成熟肽的第 31 位和第 53 位残基处显示出有趣的取代,可能涉及 S1 袋的形成,表明这些等位基因系在切割特异性方面表现出功能差异。这些结果表明,在 Oryzias 属内的物种形成之前,PSMB8 二态性就已经建立,并在通过几次物种形成事件的严格和不对称平衡选择下,已经维持了 30-60 百万年以上。