Topological comparison of circadian oscillators across species

Circadian rhythms are self-sustained biological oscillators with a roughly 24-hour cycle, regulated by molecular clocks made of nucleic acids and proteins. These clocks, found across organisms from cyanobacteria to mammals, are synchronized by environmental cues such as light. The resulting temporal information is transmitted through output pathways, coordinating rhythmic physiological processes, while the core mechanism involves a feedback loop where genes are inhibited by their protein products, completing each cycle in about 24 hours.

For my master’s thesis, I compared the topological differences of circadian oscillators across different organisms to delineate key features influencing their function. This aims to identify critical features driving their oscillations and analyze how their molecular structures support stability and adaptability. I tested random and targetted network perturbations emulating loss-of-function gene mutations, to compare the robustness and flexibility of the circadian clocks across broad phylogenetic groups encompassing Bacteria, Plants, Fungus, Insects and Mammals. The topological comparisons were based on literature on gene-regulatory network interactions inferred from experiments on Cyanobacteria, Chlamydomonas reinhardtii, Neurospora crassa, Arabidopsis thaliana, Drosophila melanogaster and Homo sapiens. The network complexity was observed to scale with organismal complexity in the number of genes (nodes), interactions between any two genes (edges), feedback loops, with fewer synthetic lethals across the network as the organismal complexity increased. As a result, robustness of these networks scaled with organismal complexity due to several factors.