Abstract
BackgroundThe cytochrome P450 (CYP) superfamily is a multifunctional hemethiolate enzyme that is widely distributed from Bacteria to Eukarya. The CYP3 family contains mainly the four subfamilies CYP3A, CYP3B, CYP3C and CYP3D in vertebrates; however, only the Actinopterygii (ray-finned fish) have all four subfamilies and detailed understanding of the evolutionary relationship of Actinopterygii CYP3 family members would be valuable.Methods and FindingsPhylogenetic relationships were constructed to trace the evolutionary history of the Actinopterygii CYP3 family genes. Selection analysis, relative rate tests and functional divergence analysis were combined to interpret the relationship of the site-specific evolution and functional divergence in the Actinopterygii CYP3 family. The results showed that the four CYP3 subfamilies in Actinopterygii might be formed by gene duplication. The first gene duplication event was responsible for divergence of the CYP3B/C clusters from ancient CYP3 before the origin of the Actinopterygii, which corresponded to the fish-specific whole genome duplication (WGD). Tandem repeat duplication in each of the homologue clusters produced stable CYP3B, CYP3C, CYP3A and CYP3D subfamilies. Acceleration of asymmetric evolutionary rates and purifying selection together were the main force for the production of new subfamilies and functional divergence in the new subset after gene duplication, whereas positive selection was detected only in the retained CYP3A subfamily. Furthermore, nearly half of the functional divergence sites appear to be related to substrate recognition, which suggests that site-specific evolution is closely related with functional divergence in the Actinopterygii CYP3 family.ConclusionsThe split of fish-specific CYP3 subfamilies was related to the fish-specific WGD, and site-specific acceleration of asymmetric evolutionary rates and purifying selection was the main force for the origin of the new subfamilies and functional divergence in the new subset after gene duplication. Site-specific evolution in substrate recognition was related to functional divergence in the Actinopterygii CYP3 family.
Highlights
The cytochromes P450 (CYPs) superfamily is a multifunctional hemethiolate enzyme that exists widely in Archaea, Eubacteria and Eukaryote
The split of fish-specific Cytochrome P450 3 (CYP3) subfamilies was related to the fish-specific whole genome duplication (WGD), and site-specific acceleration of asymmetric evolutionary rates and purifying selection was the main force for the origin of the new subfamilies and functional divergence in the new subset after gene duplication
Site-specific evolution in substrate recognition was related to functional divergence in the Actinopterygii CYP3 family
Summary
The cytochromes P450 (CYPs) superfamily is a multifunctional hemethiolate enzyme that exists widely in Archaea, Eubacteria and Eukaryote. CYPs catalyze the oxidative metabolism of lipophilic compounds including both exogenous and endogenous organic compounds, such as sterols, fatty acids, hormones, phytochemicals, antibiotics, drugs, food additives and environmental contaminants etc [3,4], involved in the development of regulatory, essential metabolism and broad defense against various pollutants. The CYP nomenclature is the official naming convention that is based mainly on the identity of amino acids; generally, a family is composed of sequences that are more than 40% identical and the subfamily members are at least 55% identical [5]. The cytochrome P450 (CYP) superfamily is a multifunctional hemethiolate enzyme that is widely distributed from Bacteria to Eukarya. The CYP3 family contains mainly the four subfamilies CYP3A, CYP3B, CYP3C and CYP3D in vertebrates; only the Actinopterygii (ray-finned fish) have all four subfamilies and detailed understanding of the evolutionary relationship of Actinopterygii CYP3 family members would be valuable
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