Département de biochimie, de microbiologie et de bio-informatique, Université Laval, Québec, Canada.
PROTEO, le réseau québécois de recherche sur la fonction, la structure et l'ingénierie des protéines, Université Laval, Québec, Canada.
Elife. 2019 Aug 27;8:e46754. doi: 10.7554/eLife.46754.
Gene duplication is a driver of the evolution of new functions. The duplication of genes encoding homomeric proteins leads to the formation of homomers and heteromers of paralogs, creating new complexes after a single duplication event. The loss of these heteromers may be required for the two paralogs to evolve independent functions. Using yeast as a model, we find that heteromerization is frequent among duplicated homomers and correlates with functional similarity between paralogs. Using evolution, we show that for homomers and heteromers sharing binding interfaces, mutations in one paralog can have structural pleiotropic effects on both interactions, resulting in highly correlated responses of the complexes to selection. Therefore, heteromerization could be preserved indirectly due to selection for the maintenance of homomers, thus slowing down functional divergence between paralogs. We suggest that paralogs can overcome the obstacle of structural pleiotropy by regulatory evolution at the transcriptional and post-translational levels.
基因复制是新功能进化的驱动力。编码同型蛋白的基因复制会导致同源和异源二聚体的形成，在单个复制事件后形成新的复合物。这些异源二聚体的丢失可能是两个同源二聚体进化出独立功能所必需的。我们使用酵母作为模型，发现复制的同源二聚体之间经常发生异源二聚化，并且与同源二聚体之间的功能相似性相关。通过进化，我们表明对于共享结合界面的同源二聚体和异源二聚体，一个同源二聚体中的突变可以对两个相互作用产生结构多效性影响，导致复合物对选择的高度相关响应。因此，由于选择维持同源二聚体，异源二聚体可以间接被保存，从而减缓同源二聚体之间的功能分歧。我们建议，通过转录和翻译后水平的调控进化，同源二聚体可以克服结构多效性的障碍。
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