Département de Biochimie, de Microbiologie et de Bio-informatique, Faculté des Sciences et de Génie Université Laval, Québec, QC G1V 0A6, Canada.
Institut de Biologie Intégrative et des Systèmes, Université Laval, Québec, QC G1V 0A6, Canada.
Science. 2024 Aug 16;385(6710):770-775. doi: 10.1126/science.ado5719. Epub 2024 Aug 15.
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.
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，一些复合物已经从由单个基因编码的同聚体转变为由重复基因编码的异聚体。这种转变可以在没有适应性进化的情况下通过分子间补偿性突变发生。在这里，我们通过实验复制和进化了一种同二聚体酶，以确定这种情况是否以及如何发生。我们鉴定了数百种使单个同二聚体失活的有害突变，但当作为复制蛋白共表达形成异二聚体时，这些突变会产生功能酶。这样一个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丧失，从而允许它们亚功能化。因此，通过基因复制，然后每个副本只有一个有害突变，就可以发生建设性的中性进化。
