Living cells are fundamentally nonequilibrium systems, meaning they constantly expend energy through seemingly one-way, irreversible processes, such as transcribing DNA into RNA, to keep life going. But how that irreversibility appears in the dynamics of individual genes has been difficult to measure.
In a new paper in npj Complexity, SFI Postdoctoral Fellow James Holehouse develops analytic tools to study that question using the canonical two-state model of gene expression, where a gene is either active or inactive, and which captures the switching behavior underlying bursty gene transcription. The new approach allows researchers to calculate a gene’s entropy-production rate, a measure of how strongly gene transcription dynamics behave like an irreversible, one-way process.
Using this coarse-grained method, Holehouse was also able to analyze several datasets of thousands of mouse genes, revealing an interesting pattern: genes tend to avoid parameter combinations associated with especially large entropy production, or high irreversibility. Gene expression may thus be influenced by physical constraints that make processes exhibiting higher levels of mesoscopic entropy production less favorable, akin to a kind of energy-expenditure minimization that operates at the level of individual genes rather than whole cells. The results open new ways to explore how nonequilibrium constraints shape gene expression.
Read the paper “Quantifying broken detailed balance in transcription” in npj Complexity. DOI: 10.1038/s44260-025-00064-w.