Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Sep 17;20(18):4585.
doi: 10.3390/ijms20184585.

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

Nikolai Genov  1   2 , Stefano Castellana  3 , Felix Scholkmann  4   5 , Daniele Capocefalo  6 , Mauro Truglio  7 , Jessica Rosati  8 , Elisa Maria Turco  9 , Tommaso Biagini  10 , Annalucia Carbone  11 , Tommaso Mazza  12 , Angela Relógio  13   14 , Gianluigi Mazzoccoli  15
Affiliations

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

Nikolai Genov et al. Int J Mol Sci. .

Abstract

Cellular, organ, and whole animal physiology show temporal variation predominantly featuring 24-h (circadian) periodicity. Time-course mRNA gene expression profiling in mouse liver showed two subsets of genes oscillating at the second (12-h) and third (8-h) harmonic of the prime (24-h) frequency. The aim of our study was to identify specific genomic, proteomic, and functional properties of ultradian and circadian subsets. We found hallmarks of the three oscillating gene subsets, including different (i) functional annotation, (ii) proteomic and electrochemical features, and (iii) transcription factor binding motifs in upstream regions of 8-h and 12-h oscillating genes that seemingly allow the link of the ultradian gene sets to a known circadian network. Our multifaceted bioinformatics analysis of circadian and ultradian genes suggests that the different rhythmicity of gene expression impacts physiological outcomes and may be related to transcriptional, translational and post-translational dynamics, as well as to phylogenetic and evolutionary components.

Keywords: biological clock; circadian rhythms; electrochemical features; rhythmic gene expression; rhythmic protein expression; ultradian rhythms.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
The upstream and downstream regions of the promoters of the different. gene sets show enriched binding sites for known transcription factors. The five transcription factor binding sites with the lowest adjusted p-value are displayed for the upstream promoter regions of the (A) 8-h (Table S1), (C) 12-h (Table S3) (E) and 24-h (Table S6) gene sets and for the downstream promoter region of the (B) 8-h (Table S2), (D) 12-h (Table S4) and (F) the 24-h (Table S5) gene sets.
Figure 2
Figure 2
Phylogenetic analysis of the promoter regions shows little variation between the promoters of the corresponding gene sets. A multiple sequence alignment and phylogenetic tree construction was performed on the upstream promoter regions of both the 8-h and the 12-h gene sets with Felsenstein nucleotide substitution model (A) and a Jukes-Cantor substitution model (B). A control set of 10 non-oscillating genes was added to the phylogenetic analysis (green markers). The red markers represent the position of the 8-h oscillating genes. The 12-h oscillating genes are the unmarked positions. A high-resolution figure is provided as Figure S2.
Figure 3
Figure 3
Electrochemical properties. (A) Box plots rendering the interquartile range (IQR) and the horizontal bar the median relative expression. Expression values that do not fall within 1.5 x IQR are outliers and are indicated by circles where appropriate. (B) Correlation matrix for parameters of non-oscillating genes. Numbers in the boxes are Spearman’s correlation coefficients. (C) Correlation matrix for parameters of oscillating genes. Numbers in the boxes are Spearman’s correlation coefficients. Asterisks represent statistically significant correlations (* p < 0.05, ** p < 0.01, *** p < 0.001).
Figure 3
Figure 3
Electrochemical properties. (A) Box plots rendering the interquartile range (IQR) and the horizontal bar the median relative expression. Expression values that do not fall within 1.5 x IQR are outliers and are indicated by circles where appropriate. (B) Correlation matrix for parameters of non-oscillating genes. Numbers in the boxes are Spearman’s correlation coefficients. (C) Correlation matrix for parameters of oscillating genes. Numbers in the boxes are Spearman’s correlation coefficients. Asterisks represent statistically significant correlations (* p < 0.05, ** p < 0.01, *** p < 0.001).
Figure 4
Figure 4
Chromosome mapping with genomic clustering of oscillatory genes in M. musculus and H. sapiens chromosomes for (A) 8-h, (B) 12-h and (C) 24-h oscillating genes (the cytoscape files are provided as Figure S7.
Figure 4
Figure 4
Chromosome mapping with genomic clustering of oscillatory genes in M. musculus and H. sapiens chromosomes for (A) 8-h, (B) 12-h and (C) 24-h oscillating genes (the cytoscape files are provided as Figure S7.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Takahashi J.S., Hong H.K., Ko C.H., McDearmon E.L. The genetics of mammalian circadian order and disorder: Implications for physiology and disease. Nat. Rev. Genet. 2008;9:764–775. doi: 10.1038/nrg2430. - DOI - PMC - PubMed
    1. Bass J., Takahashi J.S. Circadian integration of metabolism and energetics. Science. 2010;330:1349–1354. doi: 10.1126/science.1195027. - DOI - PMC - PubMed
    1. Dibner C., Schibler U., Albrecht U. The mammalian circadian timing system: Organization and coordination of central and peripheral clocks. Annu. Rev. Physiol. 2010;72:517–549. doi: 10.1146/annurev-physiol-021909-135821. - DOI - PubMed
    1. Dunlap J.C. Molecular bases for circadian clocks. Cell. 1999;96:271–290. doi: 10.1016/S0092-8674(00)80566-8. - DOI - PubMed
    1. Mermet J., Yeung J., Naef F. Systems Chronobiology: Global Analysis of Gene Regulation in a 24-Hour Periodic World. Cold Spring Harb. Perspect. Biol. 2017;9:a028720. doi: 10.1101/cshperspect.a028720. - DOI - PMC - PubMed

LinkOut - more resources