Dominant constraints on the evolution of rhythmic gene expression

Although the individual transcriptional regulators of the core circadian clock are distinct amongst different organisms, the autoregulatory feedback loops they form are conserved. This unified design principle explains how daily physiological activities oscillate across species. However, whether analogous design principles govern the gene expression output of circadian clocks is unknown. Herein, we performed a comparative analysis of rhythmic gene expression in eight diverse species and captured four common distribution patterns of cycling gene expression across these species. We hypothesized that maintenance of reduced energetic costs constrains the evolution of rhythmic gene expression. Our large-scale computational simulations support this hypothesis by showing that selection against high-energy expenditure completely regenerates all cycling gene patterns. Moreover, we find that the late- and early-phase peaks of rhythmic expression have been subjected to this type of selective pressure. Therefore, energetic costs have constricted the cycling transcriptome throughout evolutionary history.