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

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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.