[
International Worm Meeting,
2007]
Cytochrome P-450 (CYP) is a superfamily of heme-containing monooxygenases that synthesize endogenous regulatory compounds and metabolize endogenous and exogenous compounds. They are known to be responsible for bioactivation or detoxification pathways of xenobiotics in higher organisms. CYPs are evolutionarily conserved and found in most eukaryotes and prokaryotes. In C. elegans > 80 CYP genes have been identified. CYP genes in C. elegans were investigated by obtaining RNAi data available in WormBase. Twelve CYP genes obtained from 10 RNAi studies display scoreable phenotypes including growth, aging, movement, and embryonic lethality. Among these, the CYP-31A subfamily isoforms 1, 2, 3, and 5 (C01F6.3, H02I12.8, Y17G9B.3, and Y62E10A.15) displayed embryonic lethality across many studies. Microarray gene expression topology mapping shows that these genes are co-regulated with genes expressed in the germline, which further suggests a function in early meiosis or mitosis. Many CYPs are co-regulated with genes expressed in the intestine or involved in metabolism. Some isoforms are also co-regulated with neuronal genes. Although the anatomical expression pattern is currently available for only 5 CYP isoforms, 3 of these are expressed in the neurons of larval C. elegans (all 5 were also expressed in the intestine). Our results show that CYP genes are responsible for a far broader range of biological processes than previously known. While classically believed in higher organisms to be an enzyme system for metabolizing xenobiotics or synthesizing endogenous mediators, we find in C. elegans a more extensive and important role for CYPs in critical biological processes. These include roles for development and reproduction. These studies demonstrate the advantages of C. elegans as a model system to study CYP function and further extend the known biological roles of these monooxygenases.