Evidence map›Paper›PMID 35686729›Full record

ArticleeLife2022

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

Isabel Nocedal, Michael T Laub

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Article
  3. Transcriptomic and proteomic ramifications of segmental amplification inProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Article
  5. Article
  6. Symmetry facilitated the evolution of heterospecificity and high-order stoichiometry in vertebrate hemoglobin.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  7. Article
  8. Review
  9. Article
  10. Crosstalk involving two-component systems inJournal of bacteriology · 2024
    Review
  11. Review
  12. The fitness cost of spurious phosphorylation.bioRxiv : the preprint server for biology · 2023
    Article
  13. Marginal specificity in protein interactions constrains evolution of a paralogous family.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  14. Article
  15. The permissive binding theory of cancer.Frontiers in oncology · 2023
    Article
  16. Article
  17. Review
  18. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 2 institutions in 1 country.

Isabel NocedalDepartment of Biology, Massachusetts Institute of Technology, Cambridge, United States.ORCID 0000-0002-4706-1113
Michael T LaubDepartment of Biology, Massachusetts Institute of Technology, Cambridge, United States.ORCID 0000-0002-8288-7607
Howard Hughes Medical Institute · USMassachusetts Institute of Technology · US

Funding

Investigating the VapBC family of toxin-antitoxin systems in Mycobacterium tuberculosisF32GM126765 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI NOCEDAL, ISABEL · 2017 to 2020
$208k
Howard Hughes Medical InstituteNIGMS NIH HHS F32 GM126765
6 · The paper itself

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.

Indexed as

AlphaproteobacteriaEvolution, MolecularGene DuplicationMutationPhylogenySignal Transductionancestral protein reconstructionevolutionary biologygene duplicationinfectious diseasemicrobiologynonetwo-component signaling

Identifiers

PMID35686729
PMCPMC9208753
OpenAlexW4282940566

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.