Temperature-driven coordination of circadian transcriptome regulation

Abstract

The circadian rhythm is an evolutionarily-conserved molecular oscillator that enables species to anticipate rhythmic changes in their environment. At a molecular level, the core clock genes induce a circadian oscillation in thousands of genes in a tissue-specific manner, orchestrating myriad biological processes. While studies have investigated how the core clock circuit responds to environmental perturbations such as temperature, the downstream effects of such perturbations on circadian regulation remain poorly understood. By analyzing bulk-RNA sequencing of Drosophila fat bodies harvested from flies subjected to different environmental conditions, we demonstrate a highly condition-specific circadian transcriptome. Further employing a reference-based gene regulatory network (Reactome), we find evidence of increased gene-gene coordination at low temperatures and synchronization of rhythmic genes that are network neighbors. Our results point to the mechanisms by which the circadian clock mediates the fly's response to seasonal changes in temperature.

Keywords: Circadian rhythms; Drosophila melanogaster; Gene regulatory networks; Seasonal adaptation; Temperature perturbation.

Figure 1:

Experimental design. A: Method and technologies used for the V1 and V2 experiments. B: Sampling scheme of the two experiments and environmental conditions. Arrows above and below the colored bars indicate samples and replicates. The colored bars depict the light (yellow) and dark (grey) periods.

Figure 2:

Illustration of the analysis pipeline. Circadian genes are identified under each temperature (A). Estimated phases phases were mapped onto a database–derived network (B). From the network, we look for evidence of phase organization by quantifying phase difference as a function of geodesic distance on the network (C).

Figure 3:

Phase distributions. A: Z-scored TPM of detected cycling genes in the V1 experiment. (For the V2 experiment, see Supplementary Figure S2.) B: Roseplot (top) and histogram (bottom) of the phase distribution for all genes cycling at either 18°C (blue) or 25°C (orange). C: Estimated phases of genes that cycle at both temperatures. Red dots highlight the core clock genes.

Figure 4:

Temperature perturbation alters circadian gene expression globally. A: Distribution of phase differences of gene pairs with at given geodesic distances. Lines connect the median under the two temperatures. B: Observed median phase difference (points) at each geodesic distance compared to the null distribution (curves) of expected phase differences at each distance.