Rapid birth-death evolution and positive selection in detoxification-type glutathione S-transferases in mammals
Rapid birth-death evolution and positive selection in detoxification-type glutathione S-transferases in mammals
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DOI：
10.1371/journal.pone.0209336
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发表时间：
2018-12-26
期刊：
影响因子：
3.7
通讯作者：
Low, Wai Yee
中科院分区：
文献类型：
--
作者：
Tan, Hui Ming;Low, Wai Yee
谷胱甘肽 S 转移酶 (GST) 是 II 相解毒酶，可能是为了响应环境底物的变化而进化的。 GST 基因形成了一个多基因家族，在哺乳动物中，有六类：Alpha、Mu、Omega、Pi、Theta 和 Zeta。最近对 I 期解毒系统（特别是细胞色素 P450）的研究为为什么来自共同起源的基因（例如多基因家族中的基因）同时具有系统发育稳定和不稳定的基因提供了一般性解释。参与生物体核心功能（如发育和生理）的基因是稳定的，而在解毒中发挥作用的基因则不稳定，并在称为生死进化的过程中进化，其特征是频繁的基因获得和损失。出生-死亡模型在解释第一相酶以外的解毒酶进化方面的普遍性尚未得到全面探索。这项工作利用了 22 个哺乳动物物种的 383 个 Gst 基因和 300 个假基因来研究基因的获得和损失。尽管 GST 总体序列相似，但其系统发育稳定性差异很大。 Omega 和 Zeta 类的稳定 Gst 基因并未表现出从人类到负鼠的基因数量波动。这些基因在生物合成相关功能中发挥作用。不稳定的基因，包括 Alpha、Mu、Pi 和 Theta，在一个被称为生死进化的过程中经历频繁的基因获得和丢失。这四类基因成员因其在解毒中的作用而闻名。我们的正选筛选在小鼠 GSTA3 中鉴定出五个正选位点。先前的研究表明，其中两个位点（108H 和 208E）经过生化测试，被认为是具有针对有毒黄曲霉毒素 B-1-8,9-环氧化物的催化活性的重要残基。其余三个积极选择的位点针对黄曲霉毒素的功能意义值得进一步研究。
Glutathione S-Transferases (GSTs) are phase II detoxification enzymes that may have evolved in response to changes of environmental substrates. GST genes formed a multigene family and in mammals, there are six classes known as Alpha, Mu, Omega, Pi, Theta, and Zeta. Recent studies in phase I detoxification system specifically the cytochrome P450s provided a general explanation on why genes from a common origin such as those in a multigene family have both phylogenetically stable and unstable genes. Genes that participate in core functions of organisms such as development and physiology are stable whereas genes that play a role in detoxification are unstable and evolve in a process known as birth-death evolution, which is characterised by frequent gene gains and losses. The generality of the birth-death model at explaining the evolution of detoxification enzymes beyond the phase I enzyme has not been comprehensively explored. This work utilized 383 Gst genes and 300 pseudogenes across 22 mammalian species to study gene gains and losses. GSTs vary greatly in their phylogenetic stability despite their overall sequence similarity. Stable Gst genes from Omega and Zeta classes do not show fluctuation in gene numbers from human to opossum. These genes play a role in biosynthesis related functions. Unstable genes that include Alpha, Mu, Pi and Theta undergo frequent gene gain and loss in a process known as birth-death evolution. Gene members of these four classes are well known for their roles in detoxification. Our positive selection screen identified five positively selected sites in mouse GSTA3. Previous studies showed two of these sites (108H and 208E) were biochemically tested as important residues that conferred catalytic activity against the toxic aflatoxin B-1-8,9-epoxide. The functional significance against aflatoxin of the remaining three positively selected sites warrant further investigation.