Isolation and Characterization of the CYP2D6 Gene in Felidae with Comparison to Other Mammals
Isolation and Characterization of the CYP2D6 Gene in Felidae with Comparison to Other Mammals
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DOI：
10.1007/s00239-010-9424-1
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发表时间：
2011-02-01
影响因子：
3.9
通讯作者：
Weiss, Steven
中科院分区：
文献类型：
--
作者：
Schenekar, Tamara;Winkler, Kathrin A.;Weiss, Steven
高度多态性的CYP 2D 6蛋白代谢约25%的常用药物，并构成个体间广谱药物反应的基础。与对人类CYP 2D 6基因的广泛了解相反，对非人类哺乳动物中的基因知之甚少。将来自7个物种的23只猫（猫科动物）的CYP 2D 6 mRNA与另外10种哺乳动物的CYPD 6序列和人类的多种等位基因变体进行比较。一个相对较高的平均dN/dS比（0.565），特别是在猫科动物。成对dN/dS比的进化距离方面的非单调分布，这表明无论是积极的选择或保留轻微有害的突变。积极选择特定的密码子，最值得注意的是在参与底物识别和膜锚定的区域的支持和可能的影响，饮食对特定的氨基酸变化在底物结合位点进行了讨论。
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.