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

Molecular Biology and Evolution
Brian P H MetzgerPatricia J Wittkopp

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...Continue Reading

References

Jul 27, 1999·Journal of Bacteriology·H Uemura, D G Fraenkel
Jul 26, 2002·Nature·Guri GiaeverMark Johnston
Nov 26, 2002·Proceedings of the National Academy of Sciences of the United States of America·Maitreya J DunhamDavid Botstein
Mar 21, 2003·Nature·Eric E SchadtStephen H Friend
Jun 5, 2003·Molecular Biology and Evolution·Gregory A WrayLaura A Romano
May 29, 2004·Science·Jonathan M Raser, Erin K O'Shea
Jan 11, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Mark R SoboleskiWilliam P Halford
Jun 10, 2005·Genetics·Lev Y Yampolsky, Arlin Stoltzfus
Jun 22, 2005·Cellular and Molecular Life Sciences : CMLS·P J Wittkopp
Jul 8, 2005·PLoS Biology·Sean B Carroll
Sep 13, 2005·Trends in Genetics : TIG·Greg Gibson, Bruce Weir
Nov 8, 2005·Nature Genetics·Adam M Deutschbauer, Ronald W Davis
May 23, 2006·Nature Genetics·Arren Bar-EvenNaama Barkai
Oct 19, 2006·Nature Reviews. Genetics·Matthew V Rockman, Leonid Kruglyak
May 26, 2007·Science·Christian R LandryDaniel L Hartl
Jan 19, 2008·Genetics·Gregory I Lang, Andrew W Murray
Feb 19, 2008·Nature Genetics·Patricia J WittkoppAndrew G Clark
Jul 4, 2008·Trends in Genetics : TIG·Yoav GiladJonathan K Pritchard
Jul 12, 2008·Evolution; International Journal of Organic Evolution·David L Stern, Virginie Orgogozo
Sep 16, 2008·Proceedings of the National Academy of Sciences of the United States of America·Bernardo LemosDaniel L Hartl
Feb 7, 2009·Science·David L Stern, Virginie Orgogozo
Apr 11, 2009·BMC Bioinformatics·Florian HahneRobert Gentleman
Apr 11, 2009·Science·Grzegorz KudlaJoshua B Plotkin
May 16, 2009·BMC Bioinformatics·Kenneth LoRaphael Gottardo
Aug 20, 2009·Molecular Systems Biology·Zhihua ZhangJianzhi Zhang
Nov 17, 2009·Nature Biotechnology·Rupali P PatwardhanJay Shendure
May 5, 2010·Genetics·Stephane FlibotteDonald G Moerman
May 7, 2010·Genome Research·J J EmersonWen-Hsiung Li
Jul 16, 2010·Nature Reviews. Genetics·Roger P AlexanderMark B Gerstein
Apr 6, 2011·Proceedings of the National Academy of Sciences of the United States of America·Zhi Wang, Jianzhi Zhang
Jul 5, 2011·Annual Review of Genomics and Human Genetics·Wei ZhengMichael Snyder
Mar 1, 2012·Nature Biotechnology·Rupali P PatwardhanJay Shendure
Jul 24, 2012·Genome Research·Gil HornungNaama Barkai

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Citations

Sep 27, 2016·Yeast·Dawn A Thompson, Francisco A Cubillos
Sep 30, 2017·Molecular Biology and Evolution·Fabien DuveauPatricia J Wittkopp
Mar 25, 2017·Genome Biology and Evolution·Brian P H MetzgerJoseph D Coolon
May 23, 2018·Molecular Biology and Evolution·David B Stern, Keith A Crandall
Aug 21, 2018·ELife·Fabien DuveauPatricia J Wittkopp
Jan 31, 2019·PloS One·George CourcoubetisStephan Haas
Nov 12, 2016·G3 : Genes - Genomes - Genetics·Victoria L PritchardErica H Leder
Apr 28, 2019·Molecular Biology and Evolution·Jasmina UzunovićStephen I Wright
Nov 14, 2019·Proceedings. Biological Sciences·Anna LindholmHubert Rehrauer
Aug 10, 2019·Journal of Evolutionary Biology·Debika Choudhury, Supreet Saini
Nov 30, 2019·Nature Communications·Ying BaoJonathan F Wendel
Apr 23, 2020·Molecular Biology and Evolution·Emily B JosephsJohn R Stinchcombe
Jul 24, 2020·Genome Research·Gat KriegerNaama Barkai
Oct 2, 2019·Proceedings of the National Academy of Sciences of the United States of America·Andrea Hodgins-DavisPatricia J Wittkopp
May 1, 2020·Frontiers in Plant Science·Ramon Botet, Joost J B Keurentjes
Apr 15, 2020·Nature Ecology & Evolution·Lingyu WangGregory A Wray
May 8, 2020·NPJ Genomic Medicine·Rama S Singh, Bhagwati P Gupta
Dec 18, 2019·G3 : Genes - Genomes - Genetics·Corrinne E GroverJonathan F Wendel
Dec 4, 2020·Nature Reviews. Genetics·Mark S HillPatricia J Wittkopp
Feb 14, 2021·NPJ Genomic Medicine·Rama S Singh, Bhagwati P Gupta
Mar 27, 2021·Nature Reviews. Microbiology·Jan SteenselsKevin J Verstrepen
May 9, 2021·Molecular Biology and Evolution·Florian Labourel, Etienne Rajon
Apr 24, 2018·Trends in Genetics : TIG·Sarah A Signor, Sergey V Nuzhdin

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