Staff Publications

Staff Publications

  • external user (warningwarning)
  • Log in as
  • language uk
  • About

    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

    We have a manual that explains all the features 

Record number 417795
Title Initial mutations direct alternative pathways of protein evolution
Author(s) Salverda, M.L.M.; Dellus, E.; Gorter, F.A.; Debets, A.J.M.; Oost, J. van der; Hoekstra, R.F.; Tawfik, D.S.; Visser, J.A.G.M. de
Source Plos Genetics 7 (2011)3. - ISSN 1553-7404 - 11 p.
DOI https://doi.org/10.1371/journal.pgen.1001321
Department(s) Laboratory of Genetics
Microbiological Laboratory
VLAG
PE&RC
Publication type Refereed Article in a scientific journal
Publication year 2011
Keyword(s) tem-1 beta-lactamase - empirical fitness landscapes - in-vitro - natural evolution - escherichia-coli - antibiotic-resistance - sequence space - adaptation - epistasis - trajectories
Abstract Whether evolution is erratic due to random historical details, or is repeatedly directed along similar paths by certain constraints, remains unclear. Epistasis (i.e. non-additive interaction between mutations that affect fitness) is a mechanism that can contribute to both scenarios. Epistasis can constrain the type and order of selected mutations, but it can also make adaptive trajectories contingent upon the first random substitution. This effect is particularly strong under sign epistasis, when the sign of the fitness effects of a mutation depends on its genetic background. In the current study, we examine how epistatic interactions between mutations determine alternative evolutionary pathways, using in vitro evolution of the antibiotic resistance enzyme TEM-1 ß-lactamase. First, we describe the diversity of adaptive pathways among replicate lines during evolution for resistance to a novel antibiotic (cefotaxime). Consistent with the prediction of epistatic constraints, most lines increased resistance by acquiring three mutations in a fixed order. However, a few lines deviated from this pattern. Next, to test whether negative interactions between alternative initial substitutions drive this divergence, alleles containing initial substitutions from the deviating lines were evolved under identical conditions. Indeed, these alternative initial substitutions consistently led to lower adaptive peaks, involving more and other substitutions than those observed in the common pathway. We found that a combination of decreased enzymatic activity and lower folding cooperativity underlies negative sign epistasis in the clash between key mutations in the common and deviating lines (Gly238Ser and Arg164Ser, respectively). Our results demonstrate that epistasis contributes to contingency in protein evolution by amplifying the selective consequences of random mutations
Comments
There are no comments yet. You can post the first one!
Post a comment
 
Please log in to use this service. Login as Wageningen University & Research user or guest user in upper right hand corner of this page.