Verslycke Tim, Goldstone Jared V, Stegeman John J
Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA.
Mol Phylogenet Evol. 2006 Sep;40(3):760-71. doi: 10.1016/j.ympev.2006.04.017. Epub 2006 May 4.
Cytochromes P450 (CYPs) form a gene superfamily involved in the biotransformation of numerous endogenous and exogenous natural and synthetic compounds. In humans, CYP3A4 is regarded as one of the most important CYPs due to its abundance in liver and its capacity to metabolize more than 50% of all clinically used drugs. It has been suggested that all CYP3s arose from a common ancestral gene lineage that diverged between 800 and 1100 million years ago, before the deuterostome-protostome split. While CYP3s are well known in mammals and have been described in lower vertebrates, they have not been reported in non-vertebrate deuterostomes. Members of the genus Ciona belong to the tunicates, whose lineage is thought to be the most basal among the chordates, and from which the vertebrate line diverged. Here we describe the cloning, exon-intron structure, phylogeny, and estimated expression of four novel genes from Ciona intestinalis. We also describe the gene structure and phylogeny of homologous genes in Ciona savignyi. Comparing these genes with other members of the CYP clan 3, show that the Ciona sequences bear remarkable similarity to vertebrate CYP3A genes, and may be an early deuterostome CYP3 line.
细胞色素P450(CYPs)构成一个基因超家族,参与众多内源性和外源性天然及合成化合物的生物转化。在人类中,CYP3A4因其在肝脏中的丰度以及代谢超过50%的所有临床使用药物的能力,被视为最重要的细胞色素P450之一。有人提出,所有CYP3s均起源于一个共同的祖先基因谱系,该谱系在8亿至11亿年前分歧,早于后口动物 - 原口动物的分化。虽然CYP3s在哺乳动物中广为人知,并且在低等脊椎动物中也有描述,但在非脊椎后口动物中尚未见报道。海鞘属的成员属于被囊动物,其谱系被认为是脊索动物中最基础的,脊椎动物谱系由此分化而来。在这里,我们描述了来自玻璃海鞘的四个新基因的克隆、外显子 - 内含子结构、系统发育及估计的表达情况。我们还描述了萨氏海鞘中同源基因的基因结构和系统发育。将这些基因与CYP家族3的其他成员进行比较,结果表明海鞘序列与脊椎动物CYP3A基因具有显著相似性,可能是早期后口动物的CYP3谱系。