The functions of proteins generally depend on their assembly into complexes. During evolution, some complexes have transitioned from homomers encoded by a single gene to heteromers encoded by duplicate genes. This transition could occur without adaptive evolution through intermolecular compensatory mutations. Here, we experimentally duplicated and evolved a homodimeric enzyme to determine whether and how this could happen. We identified hundreds of deleterious mutations that inactivate individual homodimers but produce functional enzymes when coexpressed as duplicated proteins that heterodimerize. The structure of one such heteromer reveals how both losses of function are buffered through the introduction of asymmetry in the complex that allows them to subfunctionalize. Constructive neutral evolution can thus occur by gene duplication followed by only one deleterious mutation per duplicate.

中文翻译：

---

补偿性突变通过基因复制增强建设性中性进化


蛋白质的功能通常取决于它们组装成复合物。在进化过程中，一些复合物已从单个基因编码的同聚体转变为重复基因编码的异聚体。这种转变可以在没有通过分子间补偿突变的适应性进化的情况下发生。在这里，我们通过实验复制并进化了一种同型二聚体酶，以确定这种情况是否以及如何发生。我们发现了数百个有害突变，这些突变使单个同二聚体失活，但当共表达为异二聚体的重复蛋白质时，会产生功能性酶。一种此类异聚体的结构揭示了如何通过在复合物中引入不对称性来缓冲两种功能损失，从而使它们能够亚功能化。因此，通过基因复制可以发生建设性中性进化，然后每个重复只有一个有害突变。