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Elucidation of the evolution and generation of human paralogous chromosome regions by genome analysis

通过基因组分析阐明人类旁系同源染色体区域的进化和产生

基本信息

批准号：
11694317
负责人：
INOKO Hidetoshi
金额：
$ 4.54万
依托单位：
Tokai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

In order to clarify the gene organization of the chromosome1q21-q22 region around the CD1 (non-classical MHC antigen) genes, and to understand of the evolution of the HLA region, we have determined the nucleotide sequence of a 1.1 Mb BAC and PAC contig segment joining CD1D to FCERIA.Twelve expressed genes were located in this region with the order of CD1D-CD1A-CD1C-CD1B-CD1E-SPTA1-MNDA-IFI-16-AIM2-BL1A-FY-FCERIA from centromere to telomere. In addition, 29 genes or possibly expressed gene sequences including 20 olfactory receptor (OR) genes were also found in this region. Dot matrix analysis using the entire HLA class I region sequence versus itself revealed numerous segmental duplications of a minimal building block, whereas no such trace of duplication units was observed in the CD1 region. Therefore, these findings suggest that the human CD1 region was established prior to the HLA class I region.Some recent development of molecular biology has been interpreted as favoring the notion that the time of amphioxus emergence might be prior to two rounds of large scale genomic duplications around the time of vertebrate emergence. In order to clarify the gene organization of the region corresponding to the ancestral MHC region in amphioxus, we have determined the nucleotide sequence of in total 350, 250 bp genomic DNAs from 9 cosmid clones. Thirty-two genes or candidate gene sequences were found in these clones. It is noteworthy that the 14 of these 32 genes or candidate gene sequences showed high sequence homology to genes (RING3, h-Rev107-like, RXR, NEU-like, p44 protein, Notch, Selectin, etc.) Which were located in the human MHC region or the paralogous regions. Taken together, these findings suggest that amphioxus is a potential valuable model animal for understanding of the developmental process of the MHC region or the paralogous region.

为了阐明CD 1 ~+细胞周围染色体1 q21-q22区域的基因结构，（非经典MHC抗原）基因，并了解HLA区域的进化，我们测定了CD 1D和FCERIA之间的1.1Mb BAC和PAC重叠群片段的核苷酸序列，在该区域内定位了12个表达基因，其顺序为：CD 1D-CD 1A-CD 1C-CD 1B-CD 1 E-SPTA 1-MNDA-IFI-16-AIM 2-BL 1A-FY-FCERIA从着丝粒到端粒。此外，在该区域还发现了29个基因或可能表达的基因序列，其中包括20个嗅觉受体（OR）基因。点阵分析，使用整个HLA I类区域序列与本身揭示了许多节段性重复的一个最小的积木，而没有这样的痕迹的重复单位中观察到的CD 1区。因此，这些研究结果表明，人类的CD 1区的建立早于HLA I类区域。一些最近的分子生物学的发展已被解释为赞成的概念，文昌鱼出现的时间可能是之前的两轮大规模的基因组复制的脊椎动物出现的时间。为了阐明文昌鱼祖先MHC区域的基因结构，我们测定了9个粘粒克隆的350，250 bp基因组DNA的核苷酸序列。在这些克隆中发现了32个基因或候选基因序列。值得注意的是，这32个基因或候选基因序列中的14个与基因（RING 3、h-Rev 107-like、RXR、NEU-like、p44蛋白、Notch、Selectin等）显示出高度的序列同源性。其位于人类MHC区域或旁系同源区域。这些结果表明，文昌鱼是一个潜在的有价值的模式动物，为了解MHC区域或旁系同源区域的发育过程。