Phylogeny of Core Molecular Components of Metazoan Circadian Clocks

Abstract

The temporal organization of biological activities by circadian clocks is pivotal for the survival of organisms. Significant progress has been made in understanding the molecular foundations of animal circadian clocks through the characterization of key components, such as CLOCK, BMAL1/Cycle (CYC), Period (PER), Timeless, and Cryptochrome (CRY) in several model organisms. To determine the extent of conservation of these elements, we investigated the sequences of these genes and their paralogs across 46 animal species that encompass multiple phyla in the Metazoan kingdom to resolve the relative timing of duplication and loss events that have diversified core clock components. Using analyses of orthology and protein-protein binding predictions, we identified and characterized elements in diverse animal species. Based on these analyses, we propose a circadian molecular mechanism employed by the ancestor of all animals. We also identify derived losses and expansions of circadian elements in smaller animal clades and provide insight into the evolutionary pressures faced by their ancestors to change such an important piece of internal machinery. Our study is the first systematic analysis of the deep phylogeny of nearly all major clades of extant animals.