The cytochrome P450 genesis locus: the origin and evolution of animal cytochrome P450s

Abstract

The neighbourhoods of cytochrome P450 (CYP) genes in deuterostome genomes, as well as those of the cnidariansNematostella vectensisandAcropora digitiferaand the placozoanTrichoplax adhaerenswere examined to find clues concerning the evolution ofCYPgenes in animals.CYPgenes created by the 2R whole genome duplications in chordates have been identified. Both microsynteny and macrosynteny were used to identify genes that coexisted nearCYPgenes in the animal ancestor. We show that all 11CYPclans began in a common gene environment. The evidence implies the existence of a single locus, which we term the ‘cytochrome P450 genesis locus’, where one progenitorCYPgene duplicated to create a tandem set of genes that were precursors of the 11 animalCYPclans:CYPClans 2, 3, 4, 7, 19, 20, 26, 46, 51, 74 and mitochondrial. These earlyCYPgenes existed side by side before the origin of cnidarians, possibly with a few additional genes interspersed. The Hox gene cluster,WNTgenes, anNKgene cluster and at least oneARFgene were close neighbours to this originalCYPlocus. According to this evolutionary scenario, theCYP74clan originated from animals and not from land plants nor from a common ancestor of plants and animals. TheCYP7andCYP19families that are chordate-specific belong toCYPclans that seem to have originated in theCYPgenesis locus as well, even though this requires many gene losses to explain their current distribution. The approach to uncovering theCYPgenesis locus overcomes confounding effects because of gene conversion, sequence divergence, gene birth and death, and opens the way to understanding the biodiversity ofCYPgenes, families and subfamilies, which in animals has been obscured by more than 600 Myr of evolution.