PXD003495

PXD003495 is an original dataset announced via ProteomeXchange.

Title	Compensating the fitness costs of synonymous mutations
Description	Synonymous mutations do not change the sequence of the polypeptide but they may still influence fitness. We investigated in Salmonella enterica how four synonymous mutations in the rpsT gene (encoding ribosomal protein S20) reduce fitness (i.e. growth rate) and the mechanisms by which this cost can be genetically compensated. The reduced growth rates of the synonymous mutants were correlated with reduced levels of the rpsT transcript and S20 protein. In an adaptive evolution experiment these fitness impairments could be compensated by mutations that either caused up-regulation of S20 through increased gene dosage (due to duplications), increased transcription of the rpsT gene (due to an rpoD mutation or mutations in rpsT), or increased translation from the rpsT transcript (due to rpsT mutations). We suggest that the reduced levels of S20 in the synonymous mutants result in production of a defective subpopulation of 30S subunits lacking S20 that reduce protein synthesis and bacterial growth and that the compensatory mutations restore S20 levels and the number of functional ribosomes. Our results demonstrate how specific synonymous mutations can cause substantial fitness reductions and that many different types intra- and extragenic compensatory mutations can efficiently restore fitness. Furthermore, our study highlights that also synonymous sites can be under strong selection, which may have implications for the use of dN/dS ratios as signature for selection.
HostingRepository	PRIDE
AnnounceDate	2016-03-11
AnnouncementXML	Submission_2016-03-11_08:33:31.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Carina Sihlbom
SpeciesList	scientific name: Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720); NCBI TaxID: 99287;
ModificationList	monohydroxylated residue; methylthiolated residue; TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-01-21 01:25:44	ID requested
⏵ 1	2016-03-11 08:33:32	announced

Kn, ö, ppel A, N, ä, svall J, Andersson DI, Compensating the Fitness Costs of Synonymous Mutations. Mol Biol Evol, 33(6):1461-77(2016) [pubmed]

curator keyword: Biological

submitter keyword: Salmonella mutations, rpsT gene, ribosomal protein S20

Carina Sihlbom
contact affiliation	Proteomics Core Facility, Sahlgrenska Academy, University of Gothenburg
contact email	carina.sihlbom@gu.se
lab head
Carina Sihlbom
contact affiliation	Proteomics Core Facility / University of Gothenburg
contact email	carina.sihlbom@gu.se
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD003495
     1. Label: PRIDE project
     2. Name: Compensating the fitness costs of synonymous mutations