Progress in tracing the evolutionary paths of cytochrome P450

The state of cytochrome P450 sequence accumulation in different phyla is summarized. 12,456 P450s are currently named, with about 6000 more that are known, but not yet named. As the number of genomes sequenced moves from a few dozen to an inevitable few thousand, issues of nomenclature are discussed. Orthology will be the guiding principle for naming across related genomes such as vertebrates. Even if 1000 vertebrate genomes are sequenced there will still be only 19 CYP families in vertebrates. The variable clusters of genes in families CYP2, CYP3 and CYP4 may pose challenges for naming as 1:1 orthologs do not necessarily exist. The value of synteny across genomes is emphasized as a tool for deep time evolutionary studies of P450s in animals. There is evidence that macrosynteny may be useful in tracing the origin of animal CYP clans. The concept of saturation of sequence space is described and used to estimate how complete our knowledge is of P450s in different phyla. The special niche of filamentous fungal P450s acting in secondary metabolite gene clusters is discussed. From one quarter to one third of P450s in these fungi may be dedicated to these roles.