Evolutionary and structure-function analysis elucidates diversification of prokaryotic and eukaryotic trehalases

Trehalase catalyses the breakdown of trehalose into two glucose moieties and is ubiquitous in all organisms. Here, we provide insights into the enigmatic origin and evolution of trehalase in major species. Study of taxonomic distribution, orthology, phylogeny and functional domains indicated that trehalase possibly originates from bacteria and was transmitted to other taxa through horizontal gene transfer. Domain analysis showed that glycosyl hydrolase family 37 is present in most of the sequences and represents dominant activity during evolution, and also, illustrating that cytosolic trehalase is primitive than its transmembrane form. Furthermore, it was observed that trehalase went through domain rearrangement to facilitate its activity in adverse environmental conditions like acidic pH. Gene context analysis depicts that trehalase neighbourhood consists of sugar transport and lipid metabolism genes. This highlights their relatedness in metabolic activity and similarity in gene regulation, respectively. Evolutionary and selection pressure analysis demonstrated that trehalase genes were duplicated and evolved under purifying selection, following horizontal gene transfer. Moreover, site-specific rate of evolution emphasized conservation of functionally important residues. In comparison with acid trehalase, neutral trehalase has an extra N-terminal extension. This study serves as an instigation to understand evolution and functionality of trehalase across diverse species. Communicated by Ramaswamy H. Sarma海藻糖酶（Trehalase）可催化海藻糖分解为两个葡萄糖残基，广泛分布于所有生物类群。本研究揭示了主要物种中海藻糖酶的神秘起源与进化历程。通过对分类分布、直系同源（orthology）、系统发育（phylogeny）以及功能结构域的分析，结果表明海藻糖酶可能起源于细菌，并通过水平基因转移（horizontal gene transfer）传播至其他生物类群。 结构域分析显示，糖苷水解酶家族37（glycosyl hydrolase family 37）存在于绝大多数检测序列中，是进化过程中占据主导的活性形式；同时研究证实，胞质海藻糖酶的起源早于跨膜形式的海藻糖酶。 此外，研究观察到海藻糖酶会发生结构域重排，以适应酸性pH等不利环境下的催化活性。基因上下文分析表明，海藻糖酶的相邻基因多参与糖转运与脂质代谢过程，这分别体现了二者在代谢活动中的相关性以及基因调控机制的相似性。 进化与选择压力分析证实，海藻糖酶基因在经历水平基因转移后发生了复制，并在纯化选择（purifying selection）的作用下进化。进一步的进化位点特异性速率分析显示，具有功能重要性的氨基酸残基呈现高度保守性。与酸性海藻糖酶（acid trehalase）相比，中性海藻糖酶（neutral trehalase）额外拥有一段N端延伸序列。 本研究为解析不同物种中海藻糖酶的进化历程与功能机制提供了重要的研究基础。本文由Ramaswamy H. Sarma提交。