Ancestral reconstruction of duplicated signaling proteins reveals the evolution of signaling specificity

• DOI: 10.7554/elife.77346
• Publication Date: 2022-06-10T12:00:29Z
• Authors: Isabel Nocedal; Michael T Laub
• Keywords: Functional divergence; Crosstalk; Signaling proteins

Gene duplication is crucial to generating novel signaling pathways during evolution. However, it remains unclear how the redundant proteins produced by gene ultimately acquire new interaction specificities establish insulated paralogous pathways. Here, we used ancestral sequence reconstruction resurrect and characterize a bacterial two-component system that duplicated in α-proteobacteria. We determined of existed before immediately after this event then identified key mutations responsible for establishing specificity two systems. Just three mutations, only four interacting proteins, were sufficient extant Some these weakened interactions between systems limit crosstalk. others strengthened within system, indicating interaction, although functional, had potential be strengthened. Our work suggests protein-protein with such latent may highly amenable divergence.