Temperature compensation through kinetic regulation in biochemical oscillators

• 成果类型: Article
• 署名作者: Fu, Haochen; Fei, Chenyi; Ouyang, Qi; Tu, Yuhai
• 署名单位: University of California System; University of California San Diego; Massachusetts Institute of Technology (MIT); Peking University; International Business Machines (IBM); IBM USA
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13697
• DOI: 10.1073/pnas.2401567121
• 发表日期: 2024-05-21
• 关键词: circadian-rhythms; atpase activity; clock; phosphorylation; period; MODEL; systems; robust; INDEPENDENCE; entrainment

摘要

Nearly all circadian clocks maintain a period that is insensitive to temperature changes, a phenomenon known as temperature compensation (TC). Yet, it is unclear whether there is any common feature among different systems that exhibit TC. From a general timescale invariance, we show that TC relies on the existence of certain periodlengthening reactions wherein the period of the system increases strongly with the rates in these reactions. By studying several generic oscillator models, we show that this counterintuitive dependence is nonetheless a common feature of oscillators in the nonlinear (far -from -onset) regime where the oscillation can be separated into fast and slow phases. The increase of the period with the period -lengthening reaction rates occurs when the amplitude of the slow phase in the oscillation increases with these rates while the progression speed in the slow phase is controlled by other rates of the system. The positive dependence of the period on the period -lengthening rates balances its inverse dependence on other kinetic rates in the system, which gives rise to robust TC in a wide range of parameters. We demonstrate the existence of such period -lengthening reactions and their relevance for TC in all four model systems we considered. Theoretical results for a model of the Kai system are supported by experimental data. A study of the energy dissipation also shows that better TC performance requires higher energy consumption. Our study unveils a general mechanism by which a biochemical oscillator achieves TC by operating in parameter regimes far from the onset where period -lengthening reactions exist. Significance Although individual kinetic rates in biochemical reactions are sensitive to temperature, most circadian clocks exhibit a relatively constant period across a wide range of temperatures, a phenomenon called temperature compensation (TC). However, it remains unclear how different biochemical oscillators achieve TC. In this study, using representative biochemical oscillator models with different underlying reaction networks, we demonstrate a general kinetic regulation mechanism for TC regardless of the network structure. We find that by driving the system into a regime far from onset where the period increases strongly with at least one of the kinetic rates in the system to balance its inverse dependence on other rates, robust TC can be achieved for a wide range of parameters in different networks.