Evolutionary conservation of the circadian gene timeout in Metazoa

Abstract

Timeless(Tim) is considered to function as an essential circadian clock gene inDrosophila. Putative homologues of theDrosophila timelessgene have been identified in both mice and humans. WhileDrosophilacontains two paralogs,timelessandtimeout, acting in clock/light entrainment and chromosome integrity/photoreception, respectively, mammals contain only oneTimhomolog. In this paper, we study the phylogeny of thetimeless/timeoutfamily in 48 species [including 1 protozoan (Guillardia theta), 1 nematode (Caenorhabditis elegans), 8 arthropods and 38 chordates], for which whole genome data are available by using MEGA (Molecular Evolutionary Genetics Analysis). Phylogenetic Analysis by Maximum Likelihood (PAML) was used to analyze the selective pressure acting on metazoantimeless/timeoutgenes. Our phylogeny clearly separates insecttimelessandtimeoutlineages and shows that non-insect animalTimgenes are homologs of insecttimeout. In this study, we explored the relatively rapidly evolvingtimelesslineage that was apparently lost from most deuterostomes, including chordates, and fromCaenorhabditis elegans. In contrast, we found that thetimeoutprotein, often confusingly called “timeless” in the vertebrate literature, is present throughout the available animal genomes. Selection results showed thattimeoutis under weaker negative selection thantimeless. Finally, our phylogeny oftimeless/timeoutshowed an evolutionary conservation of the circadian clock genetimeoutin Metazoa. This conservation is in line with its multifunctionality, being essential for embryonic development and maintenance of chromosome integrity, among others.