Lost in transcriptional noise: how allelic correlation marks a trade-off between noise transmission and signal responsiveness

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Doctor of Philosophy (PhD)
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Cell and Molecular Biology
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Genetics and Genomics
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2023
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Boe, Ryan, H
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Abstract

Genetic networks should respond to signals but prevent transmission of spontaneous fluctuations. Limited data from mammalian cells suggest that noise transmission is uncommon, but systematic claims about noise transmission have been limited by the inability to directly measure it. Here we build a mathematical framework modeling allelic correlation and noise transmission, showing that allelic correlation and noise transmission correspond across model parameters and network architectures. Limiting noise transmission comes with the trade-off of being unresponsive to signals, and within responsive regimes, there is a further trade-off between response time and basal noise transmission. Analysis of allele-specific single-cell RNA-sequencing data revealed that genes encoding upstream factors in signaling pathways and cell-type specific factors have higher allelic correlation than downstream factors, suggesting they are more subject to regulation. Overall, our findings suggest that some noise transmission must result from signal responsiveness, but it can be minimized by trading-off for a slower response.

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Raj, Arjun
Date of degree
2023
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