Evolution of the repression mechanisms in circadian clocks.
Circadian clocks
Evolution
Phosphorylation
Protein sequestration
Transcription
Journal
Genome biology
ISSN: 1474-760X
Titre abrégé: Genome Biol
Pays: England
ID NLM: 100960660
Informations de publication
Date de publication:
10 01 2022
10 01 2022
Historique:
received:
03
11
2020
accepted:
07
12
2021
entrez:
11
1
2022
pubmed:
12
1
2022
medline:
5
4
2022
Statut:
epublish
Résumé
Circadian (daily) timekeeping is essential to the survival of many organisms. An integral part of all circadian timekeeping systems is negative feedback between an activator and repressor. However, the role of this feedback varies widely between lower and higher organisms. Here, we study repression mechanisms in the cyanobacterial and eukaryotic clocks through mathematical modeling and systems analysis. We find a common mathematical model that describes the mechanism by which organisms generate rhythms; however, transcription's role in this has diverged. In cyanobacteria, protein sequestration and phosphorylation generate and regulate rhythms while transcription regulation keeps proteins in proper stoichiometric balance. Based on recent experimental work, we propose a repressor phospholock mechanism that models the negative feedback through transcription in clocks of higher organisms. Interestingly, this model, when coupled with activator phosphorylation, allows for oscillations over a wide range of protein stoichiometries, thereby reconciling the negative feedback mechanism in Neurospora with that in mammals and cyanobacteria. Taken together, these results paint a picture of how circadian timekeeping may have evolved.
Sections du résumé
BACKGROUND
Circadian (daily) timekeeping is essential to the survival of many organisms. An integral part of all circadian timekeeping systems is negative feedback between an activator and repressor. However, the role of this feedback varies widely between lower and higher organisms.
RESULTS
Here, we study repression mechanisms in the cyanobacterial and eukaryotic clocks through mathematical modeling and systems analysis. We find a common mathematical model that describes the mechanism by which organisms generate rhythms; however, transcription's role in this has diverged. In cyanobacteria, protein sequestration and phosphorylation generate and regulate rhythms while transcription regulation keeps proteins in proper stoichiometric balance. Based on recent experimental work, we propose a repressor phospholock mechanism that models the negative feedback through transcription in clocks of higher organisms. Interestingly, this model, when coupled with activator phosphorylation, allows for oscillations over a wide range of protein stoichiometries, thereby reconciling the negative feedback mechanism in Neurospora with that in mammals and cyanobacteria.
CONCLUSIONS
Taken together, these results paint a picture of how circadian timekeeping may have evolved.
Identifiants
pubmed: 35012616
doi: 10.1186/s13059-021-02571-0
pii: 10.1186/s13059-021-02571-0
pmc: PMC8751359
doi:
Substances chimiques
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
17Subventions
Organisme : NHLBI NIH HHS
ID : T32 HL007622
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM118021
Pays : United States
Informations de copyright
© 2022. The Author(s).
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