A shifting mutational landscape in 6 nutritional states: stress-induced mutagenesis as a series of distinct stress input-mutation output relationships

Ram P. Maharjan, Thomas Ferenci

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)
16 Downloads (Pure)


Environmental stresses increase genetic variation in bacteria, plants, and human cancer cells. The linkage between various environments and mutational outcomes has not been systematically investigated, however. Here, we established the influence of nutritional stresses commonly found in the biosphere (carbon, phosphate, nitrogen, oxygen, or iron limitation) on both the rate and spectrum of mutations in Escherichia coli. We found that each limitation was associated with a remarkably distinct mutational profile. Overall mutation rates were not always elevated, and nitrogen, iron, and oxygen limitation resulted in major spectral changes but no net increase in rate. Our results thus suggest that stress-induced mutagenesis is a diverse series of stress input-mutation output linkages that is distinct in every condition. Environment-specific spectra resulted in the differential emergence of traits needing particular mutations in these settings. Mutations requiring transpositions were highest under iron and oxygen limitation, whereas base-pair substitutions and indels were highest under phosphate limitation. The unexpected diversity of input-output effects explains some important phenomena in the mutational biases of evolving genomes. The prevalence of bacterial insertion sequence transpositions in the mammalian gut or in anaerobically stored cultures is due to environmentally determined mutation availability. Likewise, the much-discussed genomic bias towards transition base substitutions in evolving genomes can now be explained as an environment-specific output. Altogether, our conclusion is that environments influence genetic variation as well as selection.

Original languageEnglish
Article numbere2001477
Number of pages22
JournalPLoS Biology
Issue number6
Publication statusPublished - Jun 2017
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


  • Carbohydrate Epimerases/genetics
  • Clone Cells
  • Cluster Analysis
  • DNA, Bacterial/metabolism
  • Escherichia coli K12/genetics
  • Escherichia coli Proteins/genetics
  • Fermentation
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial
  • Gene-Environment Interaction
  • INDEL Mutation
  • Models, Genetic
  • Mutagenesis
  • Mutagenesis, Insertional
  • Mutation
  • Mutation Rate
  • Mutation, Missense
  • Nutrigenomics/methods
  • Point Mutation
  • Stress, Physiological


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