Sökning: WFRF:(Chakraborty Kausik) >
Differential streng...
-
Dandage, RohanCSIR Inst Genom & Integrat Biol, New Delhi, India;AcSIR, New Delhi, India
(författare)
Differential strengths of molecular determinants guide environment specific mutational fates
- Artikel/kapitelEngelska2018
Förlag, utgivningsår, omfång ...
-
2018-05-29
-
PUBLIC LIBRARY SCIENCE,2018
-
electronicrdacarrier
Nummerbeteckningar
-
LIBRIS-ID:oai:DiVA.org:uu-364482
-
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-364482URI
-
https://doi.org/10.1371/journal.pgen.1007419DOI
Kompletterande språkuppgifter
-
Språk:engelska
-
Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
-
Ämneskategori:ref swepub-contenttype
-
Ämneskategori:art swepub-publicationtype
Anmärkningar
-
Organisms maintain competitive fitness in the face of environmental challenges through molecular evolution. However, it remains largely unknown how different biophysical factors constrain molecular evolution in a given environment. Here, using deep mutational scanning, we quantified empirical fitness of >2000 single site mutants of the Gentamicin-resistant gene (GmR) in Escherichia coli, in a representative set of physical (non-native temperatures) and chemical (small molecule supplements) environments. From this, we could infer how different biophysical parameters of the mutations constrain molecular function in different environments. We find ligand binding, and protein stability to be the best predictors of mutants' fitness, but their relative predictive power differs across environments. While protein folding emerges as the strongest predictor at minimal antibiotic concentration, ligand binding becomes a stronger predictor of mutant fitness at higher concentration. Remarkably, strengths of environment-specific selection pressures were largely predictable from the degree of mutational perturbation of protein folding and ligand binding. By identifying structural constraints that act as determinants of fitness, our study thus provides coarse mechanistic insights into the environment specific accessibility of mutational fates.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
-
Pandey, RajeshCSIR Inst Genom & Integrat Biol, CSIR Ayurgen Unit, TRISUTRA, New Delhi, India;MRC Harwell Inst, Mammalian Genet Unit, Harwell Sci & Innovat Campus, Didcot, Oxon, England
(författare)
-
Jayaraj, GopalCSIR Inst Genom & Integrat Biol, New Delhi, India;AcSIR, New Delhi, India;Max Planck Inst Biochem, Dept Cellular Biochem, Martinsried, Germany
(författare)
-
Rai, ManishCSIR Inst Genom & Integrat Biol, New Delhi, India;AcSIR, New Delhi, India
(författare)
-
Berger, DavidUppsala universitet,Zooekologi(Swepub:uu)davbe306
(författare)
-
Chakraborty, KausikCSIR Inst Genom & Integrat Biol, New Delhi, India;AcSIR, New Delhi, India
(författare)
-
CSIR Inst Genom & Integrat Biol, New Delhi, India;AcSIR, New Delhi, IndiaCSIR Inst Genom & Integrat Biol, CSIR Ayurgen Unit, TRISUTRA, New Delhi, India;MRC Harwell Inst, Mammalian Genet Unit, Harwell Sci & Innovat Campus, Didcot, Oxon, England
(creator_code:org_t)
Sammanhörande titlar
-
Ingår i:PLOS Genetics: PUBLIC LIBRARY SCIENCE14:51553-73901553-7404
Internetlänk
Hitta via bibliotek
Till lärosätets databas