VIB Laboratory for Systems Biology, Leuven, Belgium.
PLoS Biol. 2012;10(12):e1001446. doi: 10.1371/journal.pbio.1001446. Epub 2012 Dec 11.
Gene duplications are believed to facilitate evolutionary innovation. However, the mechanisms shaping the fate of duplicated genes remain heavily debated because the molecular processes and evolutionary forces involved are difficult to reconstruct. Here, we study a large family of fungal glucosidase genes that underwent several duplication events. We reconstruct all key ancestral enzymes and show that the very first preduplication enzyme was primarily active on maltose-like substrates, with trace activity for isomaltose-like sugars. Structural analysis and activity measurements on resurrected and present-day enzymes suggest that both activities cannot be fully optimized in a single enzyme. However, gene duplications repeatedly spawned daughter genes in which mutations optimized either isomaltase or maltase activity. Interestingly, similar shifts in enzyme activity were reached multiple times via different evolutionary routes. Together, our results provide a detailed picture of the molecular mechanisms that drove divergence of these duplicated enzymes and show that whereas the classic models of dosage, sub-, and neofunctionalization are helpful to conceptualize the implications of gene duplication, the three mechanisms co-occur and intertwine.
基因复制被认为有助于进化创新。然而，由于涉及的分子过程和进化力量难以重建，因此塑造复制基因命运的机制仍存在很大争议。在这里，我们研究了一大类真菌糖苷酶基因，这些基因经历了多次复制事件。我们重建了所有关键的祖先酶，并表明第一个预复制酶主要对麦芽糖样底物具有活性，对异麦芽糖样糖具有微量活性。对复活酶和现代酶的结构分析和活性测量表明，两种活性不能在单个酶中完全优化。然而，基因复制反复产生了女儿基因，其中突变优化了异麦芽糖酶或麦芽糖酶的活性。有趣的是，通过不同的进化途径，酶活性的类似转变多次出现。总之，我们的研究结果提供了一个详细的分子机制的图片，这些机制驱动这些复制酶的分化，并表明虽然剂量、亚功能和新功能化的经典模型有助于概念化基因复制的影响，但这三种机制同时发生并交织在一起。
