Evolution of the human cold/menthol receptor, TRPM8
Evolution of the human cold/menthol receptor, TRPM8
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DOI：
10.1016/j.ympev.2019.04.011
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发表时间：
2019-07-01
影响因子：
4.1
通讯作者：
Bidaux, Gabriel
中科院分区：
文献类型：
--
作者：
Blanquart, Samuel;Borowiec, Anne-Sophie;Bidaux, Gabriel
在物种适应特定生态条件的过程中，表现出多种功能或经历快速扩张和收缩的基因，如气味、信息素和味道的感觉受体，其特征是通过进化具有很大的可塑性。TRP通道家族中最令人着迷的感觉受体之一，冷和薄荷醇受体TRPM 8，在文献中受到了极大的关注。最近的研究已经报道了TRPM8通道亚型的存在，其由从选择性启动子转录并通过选择性剪接加工的选择性mRNA编码。自2000年人类基因组草图完成以来，选择性转录、选择性剪接和选择性翻译已成为基因产物多样性的主要来源，并被认为参与了高等生物复杂性的产生。在本研究中，我们研究了TRPM8基因的转录选择是否是人类冷受体TRPM8基因进化的驱动力。我们在人体组织中鉴定了33个TRPM8基因的转录选择（24个新序列）及其相关的蛋白异构体。使用比较基因组学，我们描述了人类TRPM8序列的进化在8个祖先，因为羊膜的起源，并估计在哪些祖先中的新的TRPM8变体起源。为了验证该受体的估计起源，我们对小鼠组织中的预测外显子进行了实验验证。我们的研究结果表明，在Boreoeutheria祖先的冷受体的第一个多样化的事件，和随后的分歧Simiiformes的起源。
Genes showing versatile functions or subjected to fast expansion and contraction during the adaptation of species to specific ecological conditions, like sensory receptors for odors, pheromones and tastes, are characterized by a great plasticity through evolution. One of the most fascinating sensory receptors in the family of TRP channels, the cold and menthol receptor TRPM8, has received significant attention in the literature. Recent studies have reported the existence of TRPM8 channel isoforms encoded by alternative mRNAs transcribed from alternative promoters and processed by alternative splicing. Since the first draft of the human genome was accomplished in 2000, alternative transcription, alternative splicing and alternative translation have appeared as major sources of gene product diversity and are thought to participate in the generation of complexity in higher organisms. In this study, we investigate whether alternative transcription has been a driving force in the evolution of the human forms of the cold receptor TRPM8.We identified 33 TRPM8 alternative mRNAs (24 new sequences) and their associated protein isoforms in human tissues. Using comparative genomics, we described the evolution of the human TRPM8 sequences in eight ancestors since the origin of Amniota, and estimated in which ancestors the new TRPM8 variants originated. In order to validate the estimated origins of this receptor, we performed experimental validations of predicted exons in mouse tissues. Our results suggest a first diversification event of the cold receptor in the Boreoeutheria ancestor, and a subsequent divergence at the origin of Simiiformes.