High-throughput single-cell eQTL mapping in yeast reveals how genetic variants shape rapid transcriptional responses to stress

Expression quantitative trait loci (eQTLs) — genetic variants that influence how much RNA a gene produces — have been mapped extensively in human tissues under steady-state conditions, but their role in shaping transcriptional responses to acute physiological challenge is poorly understood. A preprint posted on bioRxiv uses the tractable genetics of budding yeast to address this question at scale.

The authors deployed a high-throughput 'one-pot' single-cell RNA-sequencing approach, measuring transcript levels across a genetically diverse yeast population simultaneously before and after two distinct environmental perturbations: an acute salt stress applied to actively cycling cells, and nutrient repletion of cells following one week of starvation. By comparing eQTL maps before and after each perturbation, they characterise how genetic variants alter the magnitude, direction, and timing of transcriptional responses to stress.

The study identifies substantial genetic variation in dynamic gene expression responses that would not have been detectable from steady-state measurements alone. As a model organism study, direct extrapolation to human biology requires caution. However, the methodological framework — pairing large-scale genetic variation with single-cell dynamic transcriptomics — is likely to be applicable to more complex systems. The preprint has not yet been peer-reviewed and represents a methods and resource contribution to the fields of functional genomics and gene regulation.