Potential Conservation of Circadian Clock Proteins in the phylum Nematoda as Revealed by Bioinformatic Searches

Abstract

Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.

A Cell-Autonomous Mammalian 12 hr Clock Coordinates Metabolic and Stress Rhythms

“…More importantly, while the 12h rhythms are conserved in C. elegans , homologs of drosophila and mammalian core circadian clock as well as top 24h cycling mouse hepatic genes do not exhibit circadian rhythms under the same conditions (Figures 7D, S7H,I). The lack of circadian oscillation of canonical circadian clock genes in C. elegans have been previously reported in several studies and these genes are believed to play roles in development rather than regulating circadian rhythms in nematodes (Romanowski et al, 2014; van der Linden et al, 2010). Given that the 12h clock is conserved but not the 24h circadian clock between nematodes and mammals, this observation strongly supports our hypothesis that the 12h clock evolved ‘separately’ from the circadian clock and that the mammalian 12h clock is independent from the circadian clock.…”

Circadian rhythms identified in Caenorhabditis elegans by in vivo long-term monitoring of a bioluminescent reporter

“…In addition, our bioinformatics analysis showed that KIN-20 has a high degree of homology with its counterpart in arthropods and mammals, with a complete conservation of all regulatory and functional sites (20); thus KIN-20 is a likely target of the PF-670642 selective casein kinase 1e and δ inhibitor. Conservation of the regulatory sites between LIN-42 and PER and between CK1e/δ and KIN-20 suggests the possibility of interactions similar to those found in other species.…”

“…A dominant role for CK1-mediated protein phosphorylation in circadian timing has been described in mammals (32), Drosophila melanogaster (33), Neurospora crassa (34), and Ostreococcus tauri (35), even when the putative target proteins of CK1 in their TTFL systems are not conserved. C. elegans has only one protein, encoded by the protein kinase gene kin-20 (20), that is a homolog to the mammalian casein kinases 1e/δ. To test whether PF-670462, a CK1e and δ inhibitor and a common pharmacological modulator of the circadian period in other species, could also influence the sur-5 luminescent rhythms, we recorded the luminescence of single nematodes exposed to different concentrations of the drug.…”

“…Several proteins have been described as putative homologs to the insect/mammalian core clock genes, notably the aryl hydrocarbon receptor associated protein (AHA-1), the abnormal cell lineage 42 protein isoforms b/c (LIN-42b/c), or timeless related protein (TIM-1), which show different degrees of homology to CLOCK, PERIOD, and TIMELESS, respectively (20,49). However, these genes thus far have been reported to play developmental roles in the nematode (21)(22)(23), and none has been demonstrated to show circadian rhythmicity at the mRNA level (14,19).…”

“…Numerous circadian cycles have been described in the nematode at different levels, including behavior (locomotor activity) (10)(11)(12), physiology (defecation rate, pharyngeal pumping rate, and olfaction) (13,14), metabolism (abiotic and biotic stress tolerance, food and oxygen consumption) (15,16), protein activity and regulation (14,17,18), and gene expression (19). Recent exhaustive bioinformatics searches have identified proteins of relatively high homology to clock components from other species (20). However, these homolog genes play a key role in the developmental program of C. elegans (21)(22)(23), and their function in the circadian clock of the nematode is not clear.…”