Evolution of the Clock from Yeast to Man by Period-Doubling Folds in the Cellular Oscillator

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Abstract
Analysis of genome-wide oscillations in transcription reveals that the cell is an oscillator and an attractor and that the maintenance of a stable phenotype requires that maximums in expression in clusters of transcripts must be poised at antipodal phases around the steady state—this is the dynamic architecture of phenotype. Plots of the path through concentration phase space taken by all of the transcripts of Saccharomyces cerevisiae yield a simple three-dimensional surface. How this surface might change as period lengthens or as a cell differentiates is at the center of current work. We have shown that changes in gene expression in response to mutation or perturbation by drugs occur through a folding or unfolding of the surface described by this circle of transcripts and we suggest that the path from this 40-minute oscillation to the cell cycle and circadian rhythms takes place through a series of period-two or period-three bifurcations. These foldings in the surface of the putative attractor result in an increasingly dense set of nested trajectories in the concentrations of message and protein. Evolutionary advantage might accrue to an organism that could change period by changes in just one or a few genes as day length increased from 4 hours in the prebiotic Earth, through 8 hours during the expansion of photoautotrophs, to the present 24 hours.
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