Synonymous mutations make dramatic contributions to fitness when growth is limited by a weak-link enzyme

PLoS Genetics
JohnCarlo KristofichShelley D Copley

Abstract

Synonymous mutations do not alter the specified amino acid but may alter the structure or function of an mRNA in ways that impact fitness. There are few examples in the literature, however, in which the effects of synonymous mutations on microbial growth rates have been measured, and even fewer for which the underlying mechanism is understood. We evolved four populations of a strain of Salmonella enterica in which a promiscuous enzyme has been recruited to replace an essential enzyme. A previously identified point mutation increases the enzyme's ability to catalyze the newly needed reaction (required for arginine biosynthesis) but decreases its ability to catalyze its native reaction (required for proline biosynthesis). The poor performance of this enzyme limits growth rate on glucose. After 260 generations, we identified two synonymous mutations in the first six codons of the gene encoding the weak-link enzyme that increase growth rate by 41 and 67%. We introduced all possible synonymous mutations into the first six codons and found substantial effects on growth rate; one doubles growth rate, and another completely abolishes growth. Computational analyses suggest that these mutations affect either the stability of a stem-loop ...Continue Reading

References

Jun 26, 1990·Biochemistry·C O Gualerzi, C L Pon
Jan 12, 1987·Nucleic Acids Research·M C GanozaB G Louis
Apr 1, 1974·Proceedings of the National Academy of Sciences of the United States of America·J Shine, L Dalgarno
Sep 1, 1974·Journal of Bacteriology·F C NeidhardtD F Smith
Aug 25, 1984·Journal of Molecular Biology·L M MunsonW S Reznikoff
May 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·P Anderson, J Roth
Jun 8, 2001·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·C JacksonP Sambrook
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Nov 3, 2005·Genes & Development·Atilio Deana, Joel G Belasco
Jun 1, 1990·Applied and Environmental Microbiology·M H ZwieteringK van 't Riet
Mar 16, 2007·Structure·Tatsuya KaminishiShigeyuki Yokoyama
Aug 30, 2008·Journal of Molecular Biology·Chung-Jung TsaiRuth Nussinov
Sep 2, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sean Yu McLoughlin, Shelley D Copley
Sep 2, 2008·Nature·Angelita SimonettiBruno P Klaholz
Apr 11, 2009·Science·Grzegorz KudlaJoshua B Plotkin
Dec 17, 2009·Methods in Molecular Biology·Jason W H Wong, Gerard Cagney
Nov 6, 2010·Science·Peter A LindDan I Andersson
Nov 11, 2010·Journal of the American Chemical Society·Edward P O'BrienChristopher M Dobson
Nov 30, 2010·Current Opinion in Structural Biology·Gong Zhang, Zoya Ignatova
Jul 21, 2011·Molecular Biology and Evolution·José M CuevasRafael Sanjuán
Sep 1, 2011·Nature Reviews. Genetics·Zuben E Sauna, Chava Kimchi-Sarfaty
Apr 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·Carsten KrögerJay C D Hinton
Jul 5, 2012·PLoS Genetics·Martijn F SchenkJ Arjan G M de Visser
Jun 19, 2013·Molecular Systems Biology·Kajetan BenteleNils Blüthgen
Aug 1, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jared J GartnerYardena Samuels
Sep 28, 2013·Science·Daniel B GoodmanSriram Kosuri
Dec 21, 2013·Molecular Microbiology·Hiroki AndoTeruo Kirikae
May 3, 2014·Accounts of Chemical Research·Edward P O'BrienChristopher M Dobson
May 20, 2014·Methods in Molecular Biology·Daniel E Deatherage, Jeffrey E Barrick
Jun 11, 2014·Nature Communications·Susan F BaileyRees Kassen
May 23, 2015·PloS One·Michael BaymRoy Kishony
Sep 1, 2015·Cell Reports·Ola B NilssonGunnar von Heijne
Feb 26, 2016·Molecular Biology and Evolution·Deepa AgasheChristopher J Marx
Jun 25, 2017·Molecular Biology and Evolution·Arlin Stoltzfus, David M McCandlish

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Citations

Aug 11, 2019·Molecular Biology and Evolution·Matthew S FaberTimothy A Whitehead
Oct 5, 2019·Nucleic Acids Research·Miguel Angel MartínezMaria Nevot
Nov 21, 2019·Proceedings. Biological Sciences·Pauline D Scanlan
Aug 12, 2020·Nature Ecology & Evolution·Troy E SandbergBernhard O Palsson
Sep 9, 2020·Annual Review of Genetics·Christopher M Jakobson, Daniel F Jarosz
Oct 13, 2020·Genome Biology and Evolution·James T Van LeuvenCraig R Miller
Feb 16, 2021·Journal of Animal Breeding and Genetics = Zeitschrift Für Tierzüchtung Und Züchtungsbiologie·Deyin ZhangWeimin Wang
May 6, 2019·Cell Systems·Christopher M Jakobson, Daniel F Jarosz
Apr 18, 2021·Current Opinion in Structural Biology·Shelley D Copley
Jul 14, 2021·Genetica·Andrea CappanniniAndrea Giansanti
Sep 29, 2021·Molecular Biology and Evolution·Andrew B MorgenthalerShelley D Copley
Dec 18, 2021·Biotechnology for Biofuels·Alessandro L V CoradiniGleidson Silva Teixeira

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Methods Mentioned

BETA
protein folding
phosphotransferase
GTPase

Software Mentioned

Solver
breseq
RNAstructure
Chimera
Excel

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