Systematic Analysis of Mouse Genome Reveals Distinct Evolutionary and Functional Properties Among Circadian and Ultradian Genes

Abstract

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.

12-h clock regulation of genetic information flow by XBP1s

“…Twelve-hour oscillation of Xbp1 in C. rota was previously reported [1]. These data combined with the recent independent report of an earlier evolutionary origin of genes cycling with a 12-h period [8] provide strong support for our hypothesis that the mammalian 12-h clock evolved from the circatidal clock.…”

“…The main line of evidences supporting the existence of a cell-autonomous mammalian 12-h clock include (1) the presence of intact hepatic 12-h rhythms of gene expression in circadianclock-deficient mice in vivo under free-running conditions [1,6]; (2) the detection of cell-autonomous 12-h rhythms of gene expression in mouse embryonic fibroblasts (MEFs) in a Bmal1-independent manner [1,6]; (3) that similar genes are regulated in a 12-h rhythmic manner in different organisms, indicating evolutionary conservation of these 12-h mechanisms [1]; and (4) that genes exhibiting 12-h rhythms arose much earlier during evolution than circadian genes [1,6,8]. It is hypothesized that circatidal clock mechanisms would have developed before the divergence of the major animal clades, existing in a common ancestor, occupying bodies of water in which tidal cycles would have been as ecologically important-if not more so-than the circadian cycle [8][9][10].…”

Analysis of the circadian transcriptome of the Antarctic krill Euphausia superba

“…Castellana et al . observed that genes oscillating with a periodicity of about 12 hours are more likely to be evolutionary ancient and essential for cellular functions, suggesting that their short periodicity may reflect the periodicity of ancient clocks 49 . Short periodicities in the expression profile of several clock and clock-controlled genes in DD might suggest that not only the architecture but also the features of ancient endogenous clocks have been conserved in krill throughout speciation.…”

A Multi-Layered Study on Harmonic Oscillations in Mammalian Genomics and Proteomics

“…The different periodicity of gene expression impacts physiological outcomes [16] and may be related to transcriptional, translational and post-translational dynamics [17,18,19,20,21], as well as to phylogenetic and evolutionary components [22].…”