Allelic correlation is a marker of tradeoffs between barriers to transmission of expression variability and signal responsiveness in genetic networks

Abstract

ABSTRACTAccurately functioning genetic networks should be responsive to signals but prevent transmission of stochastic bursts of expression. Existing data in mammalian cells suggests that such transcriptional “noise” is transmitted by some genes and not others, suggesting that noise transmission is tunable, perhaps at the expense of other signal processing capabilities.However, systematic claims about noise transmission in genetic networks have been limited by the inability to directly measure noise transmission. Here we build a mathematical framework capable of modeling allelic correlation and noise transmission. We find that allelic correlation and noise transmission correspond across a broad range of model parameters and network architectures. We further find that limiting noise transmission comes with the trade-off of being unresponsive to signals, and that within the parameter regimes that are responsive to signals, there is a further trade-off between response time and basal noise transmission. Using a published allele specific single cell RNA-sequencing dataset, we found that genes with high allelic odds ratios are enriched for cell-type specific functions, and that within multiple signaling pathways, factors which are upstream in the pathway have higher allelic odds ratios than downstream factors. Overall, our findings suggest that some degree of noise transmission is required to be responsive to signals, but that minimization of noise transmission can be accomplished by trading-off for a slower response time.