Institute of Low Temperature Science, Hokkaido University, Sapporo, Japan.
Mol Biol Evol. 2019 Dec 1;36(12):2830-2841. doi: 10.1093/molbev/msz193.
The relationship between enzymes and substrates does not perfectly match the "lock and key" model, because enzymes act on molecules other than their true substrate in different catalytic reactions. Such biologically nonfunctional reactions are called "promiscuous activities." Promiscuous activities are apparently useless, but they can be an important starting point for enzyme evolution. It has been hypothesized that enzymes with low promiscuous activity will show enhanced promiscuous activity under selection pressure and become new specialists through gene duplication. Although this is the prevailing scenario, there are two major problems: 1) it would not apply to prokaryotes because horizontal gene transfer is more significant than gene duplication and 2) there is no direct evidence that promiscuous activity is low without selection pressure. We propose a new scenario including various levels of promiscuous activity throughout a clade and horizontal gene transfer. STAY-GREEN (SGR), a chlorophyll a-Mg dechelating enzyme, has homologous genes in bacteria lacking chlorophyll. We found that some bacterial SGR homologs have much higher Mg-dechelating activities than those of green plant SGRs, while others have no activity, indicating that the level of promiscuous activity varies. A phylogenetic analysis suggests that a bacterial SGR homolog with high dechelating activity was horizontally transferred to a photosynthetic eukaryote. Some SGR homologs acted on various chlorophyll molecules that are not used as substrates by green plant SGRs, indicating that SGR acquired substrate specificity after transfer to eukaryotes. We propose that horizontal transfer of high promiscuous activity is one process of new enzyme acquisition.
酶和底物之间的关系并不完全符合“锁钥”模型，因为酶在不同的催化反应中会作用于除其真正底物之外的分子。这种生物学上非功能的反应被称为“混杂活性”。混杂活性显然是无用的，但它们可以成为酶进化的重要起点。有人假设，具有低混杂活性的酶在选择压力下会表现出增强的混杂活性，并通过基因复制成为新的专业酶。尽管这是普遍的情况，但存在两个主要问题：1）它不适用于原核生物，因为水平基因转移比基因复制更为重要；2）没有直接证据表明在没有选择压力的情况下混杂活性较低。我们提出了一个新的情景，包括在一个进化枝中具有各种混杂活性水平和水平基因转移。叶绿素 a-Mg 脱螯酶 STAY-GREEN（SGR）在缺乏叶绿素的细菌中有同源基因。我们发现，一些细菌 SGR 同源物具有比绿色植物 SGR 更高的 Mg 脱螯活性，而其他则没有活性，这表明混杂活性的水平存在差异。系统发育分析表明，具有高脱螯活性的细菌 SGR 同源物是通过水平基因转移到光合真核生物中的。一些 SGR 同源物作用于各种叶绿素分子，这些分子不是绿色植物 SGR 的底物，这表明 SGR 在转移到真核生物后获得了底物特异性。我们提出，高混杂活性的水平转移是新酶获得的一个过程。
