Evolution of the P450 gene superfamily: animal-plant 'warfare', molecular drive and human genetic differences in drug oxidation.
Drug-metabolizing enzymes, such as those encoded by the cytochrome P450 genes, are noted for their high degree of interspecies and intraspecies variability. We believe that much of this diversity is the result of continuous molecularly driven coevolution of plants producing phytoalexins and animals responding with new enzymes to detoxify these chemicals. One consequence of human P450 gene evolution is polymorphism in drug metabolism, leading to marked differences in the response of individuals to the toxic and carcinogenic effects of drugs and other environmental chemicals.
Gonzalez
F J
FJ
Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Nebert
D W
DW
D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D003647:Debrisoquin / Q000378:metabolism; D005787:Gene Frequency; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010944:Plants / Q000235:genetics; D011110:Polymorphism, Genetic; D012641:Selection, Genetic
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D003647:Debrisoquin