Evidence map›Paper›PMID 26782996›Full record

ArticleMolecular biology and evolution2016

Contrasting Frequencies and Effects of cis- and trans-Regulatory Mutations Affecting Gene Expression.

Brian P H Metzger, Fabien Duveau, David C Yuan, Stephen Tryban, Bing Yang, Patricia J Wittkopp

Open access · bronzeAbstract read
In one paragraph

Article in Molecular biology and evolution, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
12.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

72 citing papers in PubMed, 127 citations in OpenAlex.

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  17. Systems genomics of salinity stress response in rice.bioRxiv : the preprint server for biology · 2024
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12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Brian P H MetzgerDepartment of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor.
Fabien DuveauDepartment of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor.
David C YuanDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor Department of Biology, Stanford University.
Stephen TrybanDepartment of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor.
Bing YangDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor.
Patricia J WittkoppDepartment of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor wittkopp@umich.edu.
University of Michigan–Ann Arbor · US

Funding

University of Michigan Training Program in Genomic ScienceT32HG000040 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sebastian Zoellner · 1995 to 2026
$16.4M
PREDOCTORAL TRAINING IN GENETICST32GM007544 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORAN, JOHN V. · 1985 to 2022
$11.3M
Evolution of Gene Expression in YeastR01GM108826 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WITTKOPP, PATRICIA JEAN · 2013 to 2015
$865k
NHGRI NIH HHS T32 HG000040NIGMS NIH HHS R01 GM108826NIGMS NIH HHS T32 GM007544
6 · The paper itself

Abstract

Heritable differences in gene expression are caused by mutations in DNA sequences encoding cis-regulatory elements and trans-regulatory factors. These two classes of regulatory change differ in their relative contributions to expression differences in natural populations because of the combined effects of mutation and natural selection. Here, we investigate how new mutations create the regulatory variation upon which natural selection acts by quantifying the frequencies and effects of hundreds of new cis- and trans-acting mutations altering activity of the TDH3 promoter in the yeast Saccharomyces cerevisiae in the absence of natural selection. We find that cis-regulatory mutations have larger effects on expression than trans-regulatory mutations and that while trans-regulatory mutations are more common overall, cis- and trans-regulatory changes in expression are equally abundant when only the largest changes in expression are considered. In addition, we find that cis-regulatory mutations are skewed toward decreased expression while trans-regulatory mutations are skewed toward increased expression. We also measure the effects of cis- and trans-regulatory mutations on the variability in gene expression among genetically identical cells, a property of gene expression known as expression noise, finding that trans-regulatory mutations are much more likely to decrease expression noise than cis-regulatory mutations. Because new mutations are the raw material upon which natural selection acts, these differences in the frequencies and effects of cis- and trans-regulatory mutations should be considered in models of regulatory evolution.

Indexed as

Gene Expression Regulation, FungalRegulatory Sequences, Nucleic AcidAllelesBase SequenceEvolution, MolecularGene ExpressionGenetic Complementation TestGlyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)MutationPromoter Regions, GeneticSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSelection, GeneticGlyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)Saccharomyces cerevisiae ProteinsTDH3 protein, S cerevisiaedistribution of mutational effectsexpression noisemutational target sizeneutral evolutionTDH3.

Identifiers

PMID26782996
PMCPMC4909133
OpenAlexW2287312813

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.