Abstract
Cell-to-cell variability (noise) is an important feature of gene expression that impacts cell fitness and development. The regulatory mechanism of this variability is not fully understood. Here we investigate the effect on gene expression noise in divergent gene pairs (DGPs). We generated reporters driven by divergent promoters, rearranged their gene order, and probed their expressions using time-lapse fluorescence microscopy and single-molecule fluorescence in situ hybridization (smFISH). We show that two genes in a co-regulated DGP have higher expression covariance compared with the separate, tandem and convergent configurations, and this higher covariance is caused by more synchronized firing of the divergent transcriptions. For differentially regulated DGPs, the regulatory signal of one gene can stochastically ‘leak' to the other, causing increased gene expression noise. We propose that the DGPs' function in limiting or promoting gene expression noise may enhance or compromise cell fitness, providing an explanation for the conservation pattern of DGPs.
Highlights
Cell-to-cell variability is an important feature of gene expression that impacts cell fitness and development
We showed that two genes in a co-regulated divergent gene pairs (DGPs) have higher covariance in their expression compared with other spatial configurations, and this higher covariance is caused by more synchronized firing of the divergent transcriptions
We proposed that the DGPs’ function in limiting/ promoting gene expression noise may enhance/compromise cell fitness, which is consistent with the observation that highly coregulated DGPs are more conserved through evolution, and differentially regulated DGPs are less conserved
Summary
Cell-to-cell variability (noise) is an important feature of gene expression that impacts cell fitness and development. For differentially regulated DGPs, the regulatory signal of one gene can stochastically ‘leak’ to the other, causing increased gene expression noise. It may provide explanation to previous observations that the conservation of DGPs is positively correlated with coexpression[23,24] We tested these ideas by combining yeast genetics, singlecell gene expression assay and bioinformatics. We examined two differentially regulated DGPs and found that the regulatory signal of one gene can stochastically ‘leak’ to the other, and in these two cases, the leakage causes increased cell-to-cell variability of gene expression. We proposed that the DGPs’ function in limiting/ promoting gene expression noise may enhance/compromise cell fitness, which is consistent with the observation that highly coregulated DGPs are more conserved through evolution, and differentially regulated DGPs are less conserved
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
