Mechanistic origins of temperature scaling in the early embryonic cell cycle.

Temperature profoundly impacts organismal physiology and ecological dynamics, particularly affecting ectothermic species and making them especially vulnerable to climate changes. Although complex physiological processes usually involve dozens of enzymes, empirically it is found that the rates of these processes often obey the Arrhenius equation, which was originally derived for single-enzyme-catalyzed reactions. Here we have examined the temperature scaling of the early embryonic cell cycle, with the goal of understanding why the Arrhenius equation approximately holds and why it breaks down at temperature extremes. Using experimental data from , and , plus published data from , and , we find that the apparent activation energies for the early embryonic cell cycle for diverse ectotherms are all similar, , which corresponds to a value of . Using computational models, we find that the approximately Arrhenius scaling and the deviations from the Arrhenius relationship at high and low temperatures can be accounted for by biphasic temperature scaling in critical individual components of the cell cycle oscillator circuit, by imbalances in the values for different partially rate-determining enzymes, or by a combination of both. Experimental studies of cycling extracts indicate that both of these mechanisms contribute to the general scaling of temperature, and in vitro studies of individual cell cycle regulators confirm that there is in fact a substantial imbalance in their values. These findings provide mechanistic insights into the dynamic interplay between temperature and complex biochemical processes, and into why biological systems fail at extreme temperatures.