1. The Evolution of Gene-Specific Transcriptional Noise Is Driven by Selection at the Pathway Level
- Author
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Julien Y. Dutheil, Natasa Puzovic, Gustavo Valadares Barroso, Max Planck Institute for Evolutionary Biology, Max-Planck-Gesellschaft, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226
- Subjects
MESH: Gene Ontology ,0301 basic medicine ,Transcription, Genetic ,MESH: Selection, Genetic ,Gene regulatory network ,Gene Expression ,Mice ,Gene expression ,Protein Interaction Mapping ,MESH: Animals ,MESH: Models, Genetic ,Protein Interaction Maps ,MESH: Protein Interaction Maps ,MESH: Evolution, Molecular ,Regulation of gene expression ,Genetics ,Natural selection ,MESH: Genomics ,Systems Biology ,food and beverages ,MESH: Transcription Factors ,Genomics ,MESH: Gene Expression Regulation ,biological networks ,MESH: Systems Biology ,expression noise ,Single-Cell Analysis ,Transcriptional noise ,MESH: Computational Biology ,Protein Binding ,inorganic chemicals ,Systems biology ,Biology ,Investigations ,complex mixtures ,Evolution, Molecular ,MESH: Gene Expression Profiling ,03 medical and health sciences ,medicine ,MESH: Protein Binding ,Mus musculus ,Animals ,Selection, Genetic ,MESH: Mice ,Gene ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Models, Genetic ,MESH: Transcription, Genetic ,MESH: Transcriptome ,Gene Expression Profiling ,MESH: Protein Interaction Mapping ,Computational Biology ,medicine.disease ,equipment and supplies ,Gene expression profiling ,030104 developmental biology ,evolution of gene expression ,Gene Ontology ,Gene Expression Regulation ,MESH: Genome-Wide Association Study ,bacteria ,Transcriptome ,MESH: Single-Cell Analysis ,Genome-Wide Association Study ,Transcription Factors - Abstract
Gene expression is a noisy process: in constant environment and genotype, cell to cell variability occurs because of randomness of biochemical reactions..., 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 transcriptional noise, in agreement with models of noise propagation within gene networks. Because transcriptional noise is under widespread selection, we argue that it constitutes an important component of the phenotype and that variance of expression is a potential target of adaptation. Stochastic gene expression should therefore be considered together with the mean expression level in functional and evolutionary studies of gene expression.
- Published
- 2017