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人类19号染色体上细胞色素P450 CYP2A - 2B - 2F亚家族基因簇的组织与进化

Organization and evolution of the cytochrome P450 CYP2A-2B-2F subfamily gene cluster on human chromosome 19.

作者信息

Hoffman S M, Fernandez-Salguero P, Gonzalez F J, Mohrenweiser H W

机构信息

Human Genome Center, Lawrence Livermore National Laboratory, CA 94551, USA.

出版信息

J Mol Evol. 1995 Dec;41(6):894-900. doi: 10.1007/BF00173169.

DOI:10.1007/BF00173169
PMID:8587134
Abstract

Cytochrome P450 genes from the CYP2A, CYP2B, and CYP2F subfamilies form a tight cluster which we have localized on the detailed physical map of human chromosome 19. The corresponding three gene subfamilies are also clustered in the mouse genome, on the region of chromosome 7 known to be syntenic to human chromosome 19. One hundred eight cosmid clones from the human P450 region were assembled into a single contig of 350 kb, restriction mapped, and probed with cDNAs from the three gene subfamilies. A total of 11 genes were identified in humans, including five from the 2A subfamily, three from the 2B subfamily, and three from the 2F subfamily; at least six of the 11 are pseudogenes. The organization of the genes, with members of the three subfamilies intermixed, indicates that the evolution of this gene cluster has been complex. The modern gene arrangement in humans is probably the result of a series of tandem duplications, plus at least one inverted duplication. The identification of all genes and pseudogenes in this cluster also makes it possible to determine the origins of some previously known variant P450 transcripts.

摘要

来自CYP2A、CYP2B和CYP2F亚家族的细胞色素P450基因形成了一个紧密的基因簇,我们已将其定位在人类19号染色体的详细物理图谱上。相应的三个基因亚家族在小鼠基因组中也成簇分布,位于已知与人类19号染色体同线的7号染色体区域。从人类P450区域获得的108个黏粒克隆被组装成一个350 kb的单一重叠群,进行了限制性图谱分析,并用来自这三个基因亚家族的cDNA进行杂交。在人类中总共鉴定出11个基因,包括来自2A亚家族的5个、来自2B亚家族的3个和来自2F亚家族的3个;这11个基因中至少有6个是假基因。这三个亚家族成员相互混杂的基因组织表明,该基因簇的进化过程很复杂。人类中现代的基因排列可能是一系列串联重复以及至少一次反向重复的结果。鉴定出该基因簇中的所有基因和假基因,也使得确定一些先前已知的变异P450转录本的起源成为可能。

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