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Cited by 3Circadian rhythm and melatoninPlant Molecular Biology ResearchEvolution and Genetic Dynamics

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Dominant constraints on the evolution of rhythmic gene expression

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Cheng, Yang, Chi, Yuhao, Sun, Linying, Wang, Guang-Zhong·2023·Computational and Structural Biotechnology Journal
DOI 10.1016/j.csbj.2023.08.035PMC PMC10492206

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Abstract

Although the individual transcriptional regulators of the core circadian clock are distinct among different organisms, the autoregulatory feedback loops they form are conserved. This unified design principle explains how daily physiological activities oscillate across species. However, it is unknown whether analogous design principles govern the gene expression output of circadian clocks. In this study, we performed a comparative analysis of rhythmic gene expression in eight diverse species and identified four common distribution patterns of cycling gene expression across these species. We hypothesized that the maintenance of reduced energetic costs constrains the evolution of rhythmic gene expression. Our large-scale computational simulations support this hypothesis by showing that selection against high-energy expenditure completely regenerates all cycling gene patterns. Moreover, we find that the peaks of rhythmic expression have been subjected to this type of selective pressure. The results suggest that selective pressure from circadian regulation efficiently removes unnecessary gene products from the transcriptome, thereby significantly impacting its evolutionary path.

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Graphical abstract CC BY-NC-ND · PubMed Central
Fig. 1 Cycling gene expression in 8 species. (A) Heatmaps of rhythmic gene expression in eight species, including Homo sapiens, Mus musculus, Drosophila melanogaster, Saccharomyces cerevisiae, Neurospora crassa, Arabidopsis thaliana, Chlamydomonas reinhardtii and Synechococus elongates. The number and proportion of identified cycling genes in each transcriptome are indicated near the bottom of the panel. Cycling genes were identified by MetaCycle with adjusted p values < 0.05 after a Benjamini-Hochberg procedure. (B) Venn diagrams displaying the intersection of cycling genes between any two species. Different colors represent different species, while the size of the circle indicates the number of cycling genes identified. The proportion of the overlaps are indicated below, with higher percentages highlighted by a darker color. Average values were used for species with two or more associated tissues/conditions.
Fig. 1 Cycling gene expression in 8 species. (A) Heatmaps of rhythmic gene expression in eight species, including Homo sapiens, Mus musculus, Drosophila melanogaster, Saccharomyces cerevisiae, Neurospora crassa, Arabidopsis thaliana, Chlamydomonas reinhardtii and Synechococus elongates. The number and proportion of identified cycling genes in each transcriptome are indicated near the bottom of the panel. Cycling genes were identified by MetaCycle with adjusted p values < 0.05 after a Benjamini-Hochberg procedure. (B) Venn diagrams displaying the intersection of cycling genes between any two species. Different colors represent different species, while the size of the circle indicates the number of cycling genes identified. The proportion of the overlaps are indicated below, with higher percentages highlighted by a darker color. Average values were used for species with two or more associated tissues/conditions.CC BY-NC-ND · PubMed Central
Fig. 2 Functional enrichment analysis of cycling genes across species. (A) The proportion of conserved pathways between any species pair. Bar plots represent the proportion of conserved pathways, which were calculated by the number of shared enriched pathways divided by the total number of enriched pathways between the two species. Different species are labeled by distinct colors and detailed comparison information is highlighted below the panel. (B) The trends of shared cycling genes across species. As more species are included, the number of shared cycling genes drops significantly. Lines of different colors represent distinct species and values obtained after logarithmic transformation are shown. (C) The trends of shared functional pathways of cycling genes across species. Only enriched pathways are included in the plot. The number of shared enriched pathways of cycling genes drops significantly as more species are considered. Lines of different colors represent distinct species and values obtained after logarithmic transformation are shown for the number of enriched pathways. (D) Dot plot showing the comparison of shared cycling genes versus their enriched pathways across species. Odds ratio of both shared cycling genes and shared pathways between species pairs are plotted, and statistical significance was determined by a Wilcoxon rank sum test (*** indicates p < 0.001). Odds ratio was determined by Fisher’s Exact Test. (E) Dot plot showing the comparison of conserved enriched pathways between and within species. Proportion of conserved enriched pathways is plotted and significance levels were determined by a Wilcoxon rank sum test (** indicates p < 0.01).
Fig. 2 Functional enrichment analysis of cycling genes across species. (A) The proportion of conserved pathways between any species pair. Bar plots represent the proportion of conserved pathways, which were calculated by the number of shared enriched pathways divided by the total number of enriched pathways between the two species. Different species are labeled by distinct colors and detailed comparison information is highlighted below the panel. (B) The trends of shared cycling genes across species. As more species are included, the number of shared cycling genes drops significantly. Lines of different colors represent distinct species and values obtained after logarithmic transformation are shown. (C) The trends of shared functional pathways of cycling genes across species. Only enriched pathways are included in the plot. The number of shared enriched pathways of cycling genes drops significantly as more species are considered. Lines of different colors represent distinct species and values obtained after logarithmic transformation are shown for the number of enriched pathways. (D) Dot plot showing the comparison of shared cycling genes versus their enriched pathways across species. Odds ratio of both shared cycling genes and shared pathways between species pairs are plotted, and statistical significance was determined by a Wilcoxon rank sum test (*** indicates p < 0.001). Odds ratio was determined by Fisher’s Exact Test. (E) Dot plot showing the comparison of conserved enriched pathways between and within species. Proportion of conserved enriched pathways is plotted and significance levels were determined by a Wilcoxon rank sum test (** indicates p < 0.01).CC BY-NC-ND · PubMed Central
Fig. 3 Conserved distribution patterns of cycling genes across species. (A) Mean expression levels of cycling genes versus other genes for each time point. Red lines represent cycling genes while green lines represent non-cycling genes in each plot. p values < 0.005 for all comparisons between the expression of cycling genes with other genes for each time point (total of 244 comparisons), Wilcoxon rank sum test. (B) Violin plots showing comparisons of rAMP between cycling genes and other non-cycling genes. Red boxes represent cycling genes while green boxes represent non-cycling genes. p < 7.046 × 10−190 in each of the 15 comparisons, Wilcoxon rank sum test. (C-D) Proportions of cycling genes in each category grouped by mean expression level (C) and rAMP. (D). Five groups were calculated, from the bottom 20% to the top 20%. Percentages were calculated as the number of cycling genes in that group divided by the total number of cycling genes identified in the cycling transcriptome of each species. Logarithmic values for both of the parameters are shown.
Fig. 3 Conserved distribution patterns of cycling genes across species. (A) Mean expression levels of cycling genes versus other genes for each time point. Red lines represent cycling genes while green lines represent non-cycling genes in each plot. p values < 0.005 for all comparisons between the expression of cycling genes with other genes for each time point (total of 244 comparisons), Wilcoxon rank sum test. (B) Violin plots showing comparisons of rAMP between cycling genes and other non-cycling genes. Red boxes represent cycling genes while green boxes represent non-cycling genes. p < 7.046 × 10−190 in each of the 15 comparisons, Wilcoxon rank sum test. (C-D) Proportions of cycling genes in each category grouped by mean expression level (C) and rAMP. (D). Five groups were calculated, from the bottom 20% to the top 20%. Percentages were calculated as the number of cycling genes in that group divided by the total number of cycling genes identified in the cycling transcriptome of each species. Logarithmic values for both of the parameters are shown.CC BY-NC-ND · PubMed Central
Fig. 4 Prediction of cycling genes based on expression level and rAMP. Results are plotted for all species (A-N), with controls indicated by slashes. Controls were defined as predictions of cycling genes without considerations for expression levels or regulation ranges. Different species are distinguished by different colors and 1000 simulations were performed for each distribution curve. Vertical lines represent the means of each distribution peak.
Fig. 4 Prediction of cycling genes based on expression level and rAMP. Results are plotted for all species (A-N), with controls indicated by slashes. Controls were defined as predictions of cycling genes without considerations for expression levels or regulation ranges. Different species are distinguished by different colors and 1000 simulations were performed for each distribution curve. Vertical lines represent the means of each distribution peak.CC BY-NC-ND · PubMed Central
Fig. 5 Energy cost constrains the cycling transcriptomes of yeast and mice. (A) Distribution of fractional cost for each gene in the cycling transcriptome of yeast and mice. Vertical lines represent the threshold for selection, which was determined by the effective population size. (B) Venn diagrams illustrate the intersection between cycling genes and genes whose expression passed the cost selection threshold in yeast and mice. Odds ratio = 10.87 and 5.23 for yeast and mice, respectively. (C) Radial bar chart visualization on the selection of co-expressed genes. Equal or greater than 95% chance to be under selection is indicated by a dash line. (D) Enrichment of cost-selected genes in both the early and late circadian expression peaks. Venn diagrams showing the overlaps between cost-selected genes and cycling genes whose phase is located in either the early or late peak. Odds ratio = 8.17 and 9.87 for yeast early and late peaks, respectively; Odds ratio = 7.04 and 3.06 for mouse early and late peaks, respectively. Fisher’s exact tests were used to determine significance levels for each enrichment.
Fig. 5 Energy cost constrains the cycling transcriptomes of yeast and mice. (A) Distribution of fractional cost for each gene in the cycling transcriptome of yeast and mice. Vertical lines represent the threshold for selection, which was determined by the effective population size. (B) Venn diagrams illustrate the intersection between cycling genes and genes whose expression passed the cost selection threshold in yeast and mice. Odds ratio = 10.87 and 5.23 for yeast and mice, respectively. (C) Radial bar chart visualization on the selection of co-expressed genes. Equal or greater than 95% chance to be under selection is indicated by a dash line. (D) Enrichment of cost-selected genes in both the early and late circadian expression peaks. Venn diagrams showing the overlaps between cost-selected genes and cycling genes whose phase is located in either the early or late peak. Odds ratio = 8.17 and 9.87 for yeast early and late peaks, respectively; Odds ratio = 7.04 and 3.06 for mouse early and late peaks, respectively. Fisher’s exact tests were used to determine significance levels for each enrichment.CC BY-NC-ND · PubMed Central

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Metadata

Authors
Cheng, Y., Chi, Y., Sun, L., & Wang, G.-Z.
Affiliations
Shanghai Institute of Nutrition and Health (CN)
Corresponding author
Wang, Guang-Zhong
ORCID
Venue
Computational and Structural Biotechnology Journal
Publisher
American Association for the Advancement of Science (AAAS)
Published
2023-01
Volume
21
Pages
4301-4311
ISSN
2001-0370 (ISSN-L)
DOI
10.1016/j.csbj.2023.08.035
PMC
PMC10492206
OpenAlex
W4386385534
Cited by
3
References
4
Citations by year
2025: 3
FWCI
0.45
Type
journal article
Language
en
Open access
Licence
Locations
  • Computational and Structural Biotechnology Journal (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Shanghai Institutes of Nutrition and Health CAS
  • Science and Technology Commission of Shanghai Municipality (2017SHZDZX01)
  • National Natural Science Foundation of China (31600960, 31871333, 81827901)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
Keywords
circadian clock, rhythmic gene expression, evolutionary constraints, energetic cost, transcriptional regulation, autoregulatory loop, comparative genomics, selection pressure, transcriptome

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Cheng, Y., Chi, Y., Sun, L., & Wang, G.-Z. (2023). Dominant constraints on the evolution of rhythmic gene expression. Computational and Structural Biotechnology Journal. https://doi.org/10.1016/j.csbj.2023.08.035