Compensatory mutations potentiate constructive neutral evolution by gene duplication

• 成果类型: Article
• 署名作者: Despres, Philippe C.; Dube, Alexandre K.; Picard, Marie-Eve; Grenier, Jordan; Shi, Rong; Landry, Christian R.
• 署名单位: Laval University; Laval University; Laval University; Laval University; Laval University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Guelph
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10172
• DOI: 10.1126/science.ado5719
• 发表日期: 2024-08-16
• 页码: 770-775
• 关键词: yeast cytosine deaminase; crystal-structure; mechanism; complexity; expression; tools

摘要

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.