Evolutaionary mechanism for the adaptive immune system as revealed by the structural analysis of the medaka major histocompatibility complex

青鳉主要组织相容性复合物的结构分析揭示了适应性免疫系统的进化机制

• 批准号: 11236205
• 负责人: NONAKA Masaru
• 金额: $ 54.14万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11236205/
• 关键词: MHC; BAC contig; Polymorphism; Evolution; Inhred Strain; 抗原提示; 塩基配列決定; メダカ; BAC; 塩基配列; ゲノム進化; 連鎖

Human MHC (major histocompatibility complex) extending over 3.6 Mb at 6p21.3 contains many genes essential for adaptive immunity. The MHC is one of the most polymorphic regions of the human genome, and this polymorphism is believed to be formed by adaptive evolution against various pathogens. To clarify MHC polymorphism in bony fish, we determined the complete nucleotide sequence of the MHC class I region of the HNl strain (Northern Japan population-derived inbred medaka) and compared it with the published sequence of the Hd-rR strain (Southern Japan population-derived inbred medaka) MHC class I region. The compared region (〜 420 kb) was divided into three segments based on degree of sequence conservation. The middle segment (〜lOO kb) was so divergent between HNI and Hd-rR that it is almost impossible to make alignment, whereas the other two segments were easily aligned with an average 96.2% nucleotide identity between HNI and Hd-rR. The middle segment encompassed two MHC class I genes and immunoproteasome subunit genes, PSMB8 and PSMB10, and one class I gene and the PSMB8 gene were extremely divergent between two strains. This result indicates that the middle segment is evolving not only by simple nucleotide substitutions but also by extensive DNA rearrangement such as duplication, deletion and insertion within the medaka species.

人类 MHC（主要组织相容性复合体）在 6p21.3 处延伸超过 3.6 Mb，包含许多对于适应性免疫至关重要的基因。 MHC是人类基因组中多态性最多的区域之一，这种多态性被认为是通过针对各种病原体的适应性进化而形成的。为了阐明硬骨鱼的MHC多态性，我们测定了HN1品系（日本北部群体的近交系青鳉）的MHC I类区域的完整核苷酸序列，并将其与Hd-rR品系（日本南部群体的近交系青鳉）MHC I类区域的公开序列进行了比较。根据序列保守程度将比较区域（〜420 kb）分为三个片段。 HNI和Hd-rR之间的中间片段(〜100 kb)差异很大，几乎不可能进行比对，而其他两个片段很容易比对，HNI和Hd-rR之间的平均核苷酸同一性为96.2%。中间段包含两个 MHC I 类基因和免疫蛋白酶体亚基基因 PSMB8 和 PSMB10，并且一个 I 类基因和 PSMB8 基因在两个菌株之间存在极大差异。这一结果表明，青鳉物种中的中间片段不仅通过简单的核苷酸取代而进化，还通过广泛的DNA重排（例如复制、删除和插入）进化。

项目成果

Ohta, Y., Powis, S.J., Lohr, R.L., Nonaka, M., Du Pasquier, L., Flajnik, M.: "Two highly divergent ancient allelic lineages of the transporter associated with antigen processing (TAP) gene in Xenopus ; further evidence for co-evolution among MHC class I"E

Ohta, Y.、Powis, S.J.、Lohr, R.L.、Nonaka, M.、Du Pasquier, L.、Flajnik, M.：“与非洲爪蟾抗原加工 (TAP) 基因相关的转运蛋白的两个高度不同的古代等位基因谱系；

Terado T, Smith S L, Nakanishi T, Nonaka M I, Kimura H, Nonaka M: "Occurrence of structural specialization of the serine protease domain of complement factor B at the emergence of jawed vertebrates and adaptive immunity"Immunogenetics. 53. 250-254 (2001)

Terado T、Smith S L、Nakanishi T、Nonaka M I、Kimura H、Nonaka M：“有颌脊椎动物出现时补体因子 B 丝氨酸蛋白酶结构域的发生和适应性免疫”免疫遗传学。

Suzuki, M.M.: "Nucleotide sequence of the MHC class I genomic region of a teleost, the medaka (Oryzias latipes)"J.Mol.Evol.. 54. 671-679 (2002)

Suzuki, M.M.：“硬骨鱼、青鳉 (Oryzias latipes) 的 MHC I 类基因组区域的核苷酸序列”J.Mol.Evol.. 54. 671-679 (2002)

Azumi, K et al.: "Genomic Analysis of Immunity in a Urochordate and the Emergence of the Vertebrate Immune System : Waiting for Godot"Immunogenetics. 55. 570-581 (2003)

Azumi, K 等人：“尾索动物免疫的基因组分析和脊椎动物免疫系统的出现：等待戈多”免疫遗传学。

Miyazawa S, Azumi K, Nonaka M: "Cloning and characterization of integrin α subunits from the solitary ascidian, Halocynthia roretzi"J. Immunol.. 166. 1710-1715 (2001)

Miyazawa S、Azumi K、Nonaka M：“来自孤生海鞘的整合素 α 亚基的克隆和表征”J. 166. 1710-1715 (2001)