Matushkin Yu.G., Morozov P.S., Morozova I.N.
Institute of Cytology and Genetics SB RAS, 630090,Novosibirsk, 10, pr.Lavrentyeva; E-mail: mat@bionet.nsc.ru
Gene alignments have been obtained for some families of the cytochrome P450 superfamily using a database and literature sources. Phylogenetic analysis was performed and the assessment of the significance of the tree topologies using the bootstrap technique followed. The evolutionary spectra of mutations have been analysed. As has been shown by multi-factor analyses, the CYP1, CYP2, CYP11 and CYP6 spectra are closely related to one another, while CYP7 and CYP21 are different from any of them. All together, they are closely related to globins and strongly different from prion protein spectra.
Mutational spectra have been revealed for the CYP2 family in three species, namely man, rat, mouse. Regression analysis showed that although the relationship among the mutational spectra of these proteins is rather close, there are species specific differences.
Linear regression coefficient (standard deviation)
It has been shown for CYP2 in one species (rat) the considerable specificity of the mutational process within one species with respect to the gene families of cytochromes P450.
Linear regression coefficient (standard deviation)
It has been shown that the evolutionary pattern of mutations in CYP21 (impairments causing adrenal hyperplasia in man) has been under a high pressure exerted by negative selection (the mutations accumulated are concentrating around a peak of 0.7, a distance between amino acids in Miyata's matrix). In CYP21 pseudogenes, most of the mutations so accumulated change considerably the physical and chemical properties of the amino acid in this position (the distribution peaks at 2.8). In the impaired alleles of the normal CYP21 gene (reading frame shift, for example), as in the individuals affected by adrenal hyperplasia, the accumulated mutations are distributed in accordance with the evolutionary pattern, therefore stabilising selection is the case. Data obtained do not provide support to the widely shared opinion that the mutations in pseudogenes are transferred by gene conversion to the unimpaired alleles of the CYP21 gene.