Expression of temperature-sensitive ion channel TRPM8 in sperm cells correlates with vertebrate evolution
Expression of temperature-sensitive ion channel TRPM8 in sperm cells correlates with vertebrate evolution
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DOI：
10.7717/peerj.1310
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发表时间：
2015-10-13
期刊：
影响因子：
2.7
通讯作者：
Goswami, Chandan
中科院分区：
文献类型：
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作者：
Majhi, Rakesh Kumar;Saha, Somdatta;Goswami, Chandan
瞬时受体势阳离子通道，亚家族Melastatin，成员8(TRPM8)参与检测低温，不同的有毒化合物，并在细胞水平上执行热和化学敏感反应。在这里，我们通过分析不同物种的序列来探索TRPM8的分子进化。我们阐明了TRPM8的几个区域具有不同程度的选择压力，但第4-5个跨膜区保持高度保守。同步性分析表明，自脊椎动物起源以来，TRPM8基因与骨形态发生因子SPP2连锁。TRPM8，尤其是它的N-末端区域，在人类群体中似乎具有很高的变异性。我们在1092个人类基因组中发现了16,656个TRPM8变异，其中最常见的变异是SNPs、插入和缺失。根据Polyphen V2、SIFT和Grantham偏差评分的支持，总共有692个错义突变被映射到人类TRPM8蛋白上，其中509似乎是本质上的错义突变。利用一种高度特异的抗体，我们证明了TRPM8在大鼠的睾丸和从鱼类到高等哺乳动物的不同脊椎动物的精子细胞中都有内源性表达。我们假设TRPM8是在脊椎动物进化过程中出现的(约450年)。我们认为，TRPM8在精子细胞中的表达及其在调节精子功能中的作用是指导其分子进化的重要因素，这些认识可能具有医学意义。
Transient Receptor Potential cation channel, subfamily Melastatin, member 8 (TRPM8) is involved in detection of cold temperature, different noxious compounds and in execution of thermo- as well as chemo-sensitive responses at cellular levels. Here we explored the molecular evolution of TRPM8 by analyzing sequences from various species. We elucidate that several regions of TRPM8 had different levels of selection pressure but the 4th-5th transmembrane regions remain highly conserved. Analysis of synteny suggests that since vertebrate origin, TRPM8 gene is linked with SPP2, a bone morphogen. TRPM8, especially the N-terminal region of it, seems to be highly variable in human population. We found 16,656 TRPM8 variants in 1092 human genomes with top variations being SNPs, insertions and deletions. A total of 692 missense mutations are also mapped to human TRPM8 protein of which 509 seem to be delateroiours in nature as supported by Polyphen V2, SIFT and Grantham deviation score. Using a highly specific antibody, we demonstrate that TRPM8 is expressed endogenously in the testis of rat and sperm cells of different vertebrates ranging from fish to higher mammals. We hypothesize that TRPM8 had emerged during vertebrate evolution (ca 450 MYA). We propose that expression of TRPM8 in sperm cell and its role in regulating sperm function are important factors that have guided its molecular evolution, and that these understandings may have medical importance.