Comparative study of circadian clock models, in search of processes promoting oscillation

Gen Kurosawa, Atsushi Mochizuki, Yoh Iwasa

研究成果: Contribution to journalArticle査読

52 被引用数 (Scopus)

抄録

We study simple models for circadian rhythm, and examine the condition in which the equilibrium is unstable, generating a sustained oscillation. In the models, a clock gene(s) is transcribed to produce mRNAs, which are translated to produce proteins that suppress the transcription of the clock gene(s). First, using a Lyapunov function, we prove under very general conditions that two-variable models cannot generate a stable oscillation, implying that additional structures are needed for the model to generate a sustainable rhythm. By comparing several models of different complexities using the Routh-Hurwitz criteria of stability, we show that a sustained oscillation is more likely to occur if the cell is compartmentalized and the proteins need to be transported from the cytosol to the nucleus, if the proteins have to be modified before entering the nucleus, if the kinetics of transcription inhibition or the transport to the nucleus have cooperativity with a nonlinear dependence on the substrate concentration, or if the products of two clock genes form a heterodimer that suppresses both of their own genes. We discuss the implications of these results.

本文言語英語
ページ(範囲)193-208
ページ数16
ジャーナルJournal of Theoretical Biology
216
2
DOI
出版ステータス出版済み - 1 1 2002

All Science Journal Classification (ASJC) codes

  • 統計学および確率
  • モデリングとシミュレーション
  • 生化学、遺伝学、分子生物学(全般)
  • 免疫学および微生物学(全般)
  • 農業および生物科学(全般)
  • 応用数学

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