Petalcorin Mark I R, Joshua George W, Agapow Paul-Michael, Dolphin Colin T
Section of Molecular Genetics, Pharmaceutical Science Research Division, Franklin-Wilkins Building, 150 Stamford Street, King's College London, London SE1 9NN, UK.
Gene. 2005 Feb 14;346:83-96. doi: 10.1016/j.gene.2004.09.021. Epub 2004 Dec 15.
The flavin-containing monooxygenase (FMO) gene family is conserved and ancient with representatives present in almost all phyla so far examined. The genes encode FAD-, NADP- and O(2)-dependent enzymes that catalyse oxygenation of soft-nucleophilic heteroatom centres in a range of substrates. Although usually classified as xenobiotic-metabolising enzymes, examples of FMOs exist that have evolved to metabolise specific endogenous substrates as part of a discrete physiological process. The genome of Caenorhabditis elegans contains five predicted genes encoding putative homologs of mammalian FMOs, K08C7.2, K08C7.5, Y39A1A.19, F53F4.5 and H24K24.5, which we have named fmo and numbered fmo-1 to fmo-5, respectively. As a first step towards determining their functional role(s), we have experimentally characterised these C. elegans fmo genes including analysing reporter gene expression patterns and RNAi phenotypes. Two major gene expression patterns were observed, either intestinal or hypodermal, but no gross RNAi phenotypes were found possibly due to functional redundancy. The internal structures of fmo-2, fmo-3 and fmo-4 have been compared with orthologs identified in the related nematode C. briggsae. For each orthologous pair, a global comparison of the paired upstream intergenic regions was performed and a number of conserved noncoding sequences, which may represent potential cis-regulatory elements, identified. Phylogenetic analysis reveals that several of the fmo homologs are the result of gene duplication along the lineage leading to the nematodes.
含黄素单加氧酶（FMO）基因家族保守且古老，在目前已检测的几乎所有门中都有代表。这些基因编码依赖黄素腺嘌呤二核苷酸（FAD）、烟酰胺腺嘌呤二核苷酸磷酸（NADP）和氧气（O₂）的酶，可催化一系列底物中软亲核杂原子中心的氧化反应。尽管FMO通常被归类为异源生物代谢酶，但也存在一些已进化为代谢特定内源性底物的FMO实例，作为离散生理过程的一部分。秀丽隐杆线虫的基因组包含五个预测基因，编码哺乳动物FMO的假定同源物，即K08C7.2、K08C7.5、Y39A1A.19、F53F4.5和H24K24.5，我们将其命名为fmo，并分别编号为fmo - 1至fmo - 5。作为确定它们功能作用的第一步，我们通过实验对这些秀丽隐杆线虫fmo基因进行了表征，包括分析报告基因表达模式和RNA干扰（RNAi）表型。观察到两种主要的基因表达模式，即肠道或皮下表达，但未发现明显的RNAi表型，可能是由于功能冗余。已将fmo - 2、fmo - 3和fmo - 4的内部结构与相关线虫嗜热栖热放线菌中鉴定的直系同源物进行了比较。对于每对直系同源物，对配对的上游基因间区域进行了全局比较，并鉴定了一些可能代表潜在顺式调控元件的保守非编码序列。系统发育分析表明，几个fmo同源物是线虫谱系中基因复制的结果。
