Ancestral reconstruction of duplicated signaling proteins reveals the evolution of signaling specificity
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elife-77346-v2.pdf
Description
Published version
Size
1.95 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s) •
Nocedal, Isabel
Laub, Michael T
Date Issued
2022
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Citation
Nocedal, Isabel and Laub, Michael T. 2022. "Ancestral reconstruction of duplicated signaling proteins reveals the evolution of signaling specificity." eLife, 11.
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Howard Hughes Medical Institute
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.7554/ELIFE.77346