Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, United States.
Elife. 2022 Jun 10;11:e77346. doi: 10.7554/eLife.77346.
Gene duplication is crucial to generating novel signaling pathways during evolution. However, it remains unclear how the redundant proteins produced by gene duplication ultimately acquire new interaction specificities to establish insulated paralogous signaling pathways. Here, we used ancestral sequence reconstruction to resurrect and characterize a bacterial two-component signaling system that duplicated in α-proteobacteria. We determined the interaction specificities of the signaling proteins that existed before and immediately after this duplication event and then identified key mutations responsible for establishing specificity in the two systems. Just three mutations, in only two of the four interacting proteins, were sufficient to establish specificity of the extant systems. Some of these mutations weakened interactions between paralogous systems to limit crosstalk. However, others strengthened interactions within a system, indicating that the ancestral interaction, although functional, had the potential to be strengthened. Our work suggests that protein-protein interactions with such latent potential may be highly amenable to duplication and divergence.
基因复制对于在进化过程中产生新的信号通路至关重要。然而，目前尚不清楚由基因复制产生的冗余蛋白最终如何获得新的相互作用特异性，从而建立独立的同源信号通路。在这里，我们使用祖先序列重建技术复活并表征了在α-变形菌中复制的细菌双组分信号系统。我们确定了在这一复制事件之前和之后存在的信号蛋白的相互作用特异性，然后确定了导致两个系统特异性建立的关键突变。仅在四个相互作用的蛋白质中的两个中，三个突变就足以建立现有系统的特异性。这些突变中的一些削弱了同源系统之间的相互作用，以限制串扰。然而，其他突变则增强了系统内的相互作用，表明虽然祖先的相互作用具有功能性，但它有可能被加强。我们的工作表明，具有这种潜在可能性的蛋白质-蛋白质相互作用可能非常适合复制和分化。
