高原鼢鼠和高原鼠兔CYP3A25基因的分子表征及功能分析

Molecular characterization and functional analysisof CYP3A2 gene in plateau zokor and plateau pika

摘要:

【目的】 探究高原鼢鼠（Eospalax baileyi）和高原鼠兔（Ochotona curzoniae）CYP3A25 基因的分子结构及蛋白质的三维构象差异。【方法】 检测高原鼢鼠和高原鼠兔CYP3A25 基因外显子的核苷酸序列情况，并结合其他7 种啮齿动物分析其氨基酸序列和蛋白质空间构象差异。【结果】 在PCR 结果检测中成功获得高原鼢鼠和高原鼠兔CYP3A25 基因CDS 区，长度均为1 307 bp，并检测出基因序列差异及蛋白质空间构象差异。系统发育树构建发现高原鼢鼠与色列盲鼹鼠（Nannospalax galili）属于同一分支，高原鼠兔更趋同于智人（Homo sapiens）。对CYP3A25 基因序列差异介导蛋白质空间构象改变分析后，发现高原鼢鼠和高原鼠兔相较小家鼠都有3 个氨基酸序列差异导致的蛋白质空间构象改变。【结论】 研究表明不同物种CYP3A25 基因存在较大的序列差异，并且这种序列差异影响了蛋白质的空间构象。说明不同物种在CYP3A25 基因的分子表征和潜在的解毒代谢能力上存在较大差异。研究为理解不同物种的解毒代谢基因差异提供了理论依据。

Abstract:

【Objective】 This study aimed toinvestigate the molecular structure and spatial conformation of the CYP3A25 gene in plateau zokor （Eospalax baileyi） and plateau pikas （Ochotona curzoniae）.【Method】 Nucleotidesequences of the CYP3A25 gene exons were detectedin both species and，and amino acid sequences and protein spatialconformations were analyzed in comparison with seven other rodent species.【Result】 PCR successfully amplifiedtheCDS region of the 1 307 bp ‐ long CYP3A25 genefor bothzokors and pikas，revealingdifferences in gene sequenceand protein spatial conformation. A phylogenetic tree was constructed， demonstrating that the plateau zokorand the blind mole（Nannospalax galili）were closely related，while the plateau pika was more comparable to humans（Homo sapiens）. Analysis of CYP3A25 gene variation revealedthree amino acid mutations in plateau zokor and plateaupika，resulting in changes to protein spatial conformation compared to Mus.【Conclusion】 This study identifiessignificantsequence differences in the CYP3A25 gene among different species，impacting the spatial conformation ofproteins. These findings suggestimportant variations in molecular characteristics and potential detoxification metabolismacross species， providing insights into genetic differences in detoxification pathways.