Warner S C, Finta C, Zaphiropoulos P G
Center for Nutrition and Toxicology, Department of Biosciences at NOVUM, Karolinska Institute, Huddinge, Sweden.
Mol Biol Evol. 2001 Oct;18(10):1841-8. doi: 10.1093/oxfordjournals.molbev.a003726.
The cytochrome P450 2C (CYP2C) gene locus was found to include a novel exon 1 sequence with high similarity to the canonical exon 1 of CYP2C18. Rapid amplification of cDNA ends (RACE) and PCR amplifications of human liver cDNA revealed the presence of several intergenic species containing the CYP2C18 exon 1-like sequence spliced to different combinations of exonic and intronic sequences from the CYP2C9 gene. One splice variant was found to have an open reading frame starting at the canonical translation initiation codon of the CYP2C18 exon 1-like sequence. Another variant consisted of the nine typical CYP2C9 exons spliced after the CYP2C18 exon 1-like sequence through a segment of CYP2C9 5' flanking sequences. Moreover, analysis of bacterial artificial chromosome (BAC) clones revealed that the CYP2C18 exon 1-like sequence was located in the intergenic region between the CYP2C19 and CYP2C9 genes. The finding that a solitary exon is spliced with sequences from a neighboring gene may be interpreted as representing a general evolutionary mechanism aimed at using the full expression potential of a cell's genomic informational content.
细胞色素P450 2C(CYP2C)基因座被发现包含一个与CYP2C18的典型外显子1序列高度相似的新外显子1序列。对人肝脏cDNA进行cDNA末端快速扩增(RACE)和PCR扩增,结果显示存在几种基因间物种,它们包含与CYP2C9基因外显子和内含子序列的不同组合拼接的CYP2C18外显子1样序列。发现一种剪接变体具有一个开放阅读框,该开放阅读框始于CYP2C18外显子1样序列的典型翻译起始密码子。另一种变体由九个典型的CYP2C9外显子组成,这些外显子通过一段CYP2C9 5'侧翼序列在CYP2C18外显子1样序列之后进行拼接。此外,对细菌人工染色体(BAC)克隆的分析表明,CYP2C18外显子1样序列位于CYP2C19和CYP2C9基因之间的基因间区域。一个单独的外显子与相邻基因的序列进行拼接这一发现,可能被解释为代表了一种旨在利用细胞基因组信息内容的全部表达潜力的普遍进化机制。