Karl-Franzens Universität Graz, Institut für Zoologie, Universitätsplatz 2, A-8010 Graz, Austria.
J Mol Evol. 2011 Feb;72(2):222-31. doi: 10.1007/s00239-010-9424-1. Epub 2010 Dec 28.
The highly polymorphic CYP2D6 protein metabolizes about 25% of commonly used drugs and underlies a broad spectrum of drug responses among individuals. In contrast to extensive knowledge on the human CYP2D6 gene, little is known about the gene in non-human mammals. CYP2D6 mRNA from 23 cats (Felidae) spanning seven species were compared to available CYPD6 sequences in ten additional mammals and multiple allelic variants in humans. A relatively high mean dN/dS ratio (0.565) was observed, especially within Felidae. Pairwise dN/dS ratios were non-monotonically distributed with respect to evolutionary distance suggesting either positive selection or retention of slightly deleterious mutations. Positive selection on specific codons, most notably in regions involved in substrate recognition and membrane anchoring is supported and the possible influence of diet on specific amino acid changes in substrate binding sites is discussed.
高度多态性的 CYP2D6 蛋白代谢大约 25%的常用药物，并且在个体之间存在广泛的药物反应。与人类 CYP2D6 基因的广泛知识相比，关于非人类哺乳动物的 CYP2D6 基因知之甚少。比较了来自 23 只猫（猫科动物）的 CYP2D6 mRNA，跨越七个物种，与其他十种哺乳动物和人类中的多种等位基因变体的可用 CYPD6 序列进行了比较。观察到相对较高的平均 dN/dS 比值（0.565），特别是在猫科动物中。成对的 dN/dS 比值与进化距离不成单调分布，这表明存在正选择或保留略有有害突变。对特定密码子的正选择得到支持，特别是在涉及底物识别和膜锚定的区域，并且讨论了饮食对底物结合位点中特定氨基酸变化的可能影响。
