The Evolution of Gene-Specific Transcriptional Noise Is Driven by Selection at the Pathway Level

Genetics
Gustavo Valadares BarrosoJulien Y Dutheil

Abstract

Biochemical reactions within individual cells result from the interactions of molecules, typically in small numbers. Consequently, the inherent stochasticity of binding and diffusion processes generates noise along the cascade that leads to the synthesis of a protein from its encoding gene. As a result, isogenic cell populations display phenotypic variability even in homogeneous environments. The extent and consequences of this stochastic gene expression have only recently been assessed on a genome-wide scale, owing, in particular, to the advent of single-cell transcriptomics. However, the evolutionary forces shaping this stochasticity have yet to be unraveled. Here, we take advantage of two recently published data sets for the single-cell transcriptome of the domestic mouse Mus musculus to characterize the effect of natural selection on gene-specific transcriptional stochasticity. We show that noise levels in the mRNA distributions (also known as transcriptional noise) significantly correlate with three-dimensional nuclear domain organization, evolutionary constraints on the encoded protein, and gene age. However, the position of the encoded protein in a biological pathway is the main factor that explains observed levels of tr...Continue Reading

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Citations

Aug 21, 2018·ELife·Fabien DuveauPatricia J Wittkopp
May 16, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Kang Hao CheongMichael C Jones
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Aug 28, 2021·International Journal of Molecular Sciences·Karolina MajewskaAgnieszka Kołowerzo-Lubnau
Sep 7, 2021·Frontiers in Genetics·Jing LiEve Syrkin Wurtele

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Datasets Mentioned

BETA
GSE42268

Methods Mentioned

BETA
protein folding
Hi-C
PCA
Quartz-Seq

Software Mentioned

graphite
ade4 R
nlme R
Ensembl
iRefR
topGO
R
logisticPCA R
rms
Reactome PA package

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