Systematic analysis of mouse genome reveals distinct evolutionary and functional properties among circadian and ultradian genes

In living organisms, biological clocks regulate 24 h (circadian) molecular, physiological, and behavioral rhythms to maintain homeostasis and synchrony with predictable environmental changes, in particular with those induced by Earth's rotation on its axis. Harmonics of these circadian rhythms having periods of 8 and 12 h (ultradian) have been documented in several species. In mouse liver, harmonics of the 24-h period of gene transcription hallmarked genes oscillating with a frequency two or three times faster than circadian periodicity. Many of these harmonic transcripts enriched pathways regulating responses to environmental stress and coinciding preferentially with subjective dawn and dusk. At this time, the evolutionary history of genes with rhythmic expression is still poorly known and the role of length-of-day changes due to Earth's rotation speed decrease over the last four billion years is totally ignored. We hypothesized that ultradian and stress anticipatory genes would be more evolutionarily conserved than circadian genes and background non-oscillating genes. To investigate this issue, we performed broad computational analyses of genes/proteins oscillating at different frequency ranges across several species and showed that ultradian genes/proteins, especially those oscillating with a 12-h periodicity, are more likely to be of ancient origin and essential in mice. In summary, our results show that genes with ultradian transcriptional patterns are more likely to be phylogenetically conserved and associated with the primeval and inevitable dawn/dusk transitions.