Epistatic interactions determine the mutational pathways and coexistence of lineages in clonal Escherichia coli populations

Ram Prasad Maharjan*, Thomas Ferenci

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


Understanding how diversity emerges in a single niche is not fully understood. Rugged fitness landscapes and epistasis between beneficial mutations could explain coexistence among emerging lineages. To provide an experimental test of this notion, we investigated epistasis among four pleiotropic mutations in rpoS, mglD, malT, and hfq present in two coexisting lineages that repeatedly fixed in experimental populations of Escherichia coli. The mutations were transferred into the ancestral background individually or in combination of double or triple alleles. The combined competitive fitness of two or three beneficial mutations from the same lineage was consistently lower than the sum of the competitive fitness of single mutants-a clear indication of negative epistasis within lineages. We also found sign epistasis (i.e., the combined fitness of two beneficial mutations lower than the ancestor), not only from two different lineages (i.e., hfq and rpoS) but also from the same lineage (i.e., mglD and malT). The sign epistasis between loci of different lineages indeed indicated a rugged fitness landscape, providing an epistatic explanation for the coexistence of distinct rpoS and hfq lineages in evolving populations. The negative and sign epistasis between beneficial mutations within the same lineage can further explain the order of mutation acquisition.

Original languageEnglish
Pages (from-to)2762-2768
Number of pages7
Issue number9
Publication statusPublished - Sep 2013
Externally publishedYes


  • Beneficial mutations
  • Chemostat
  • Experimental evolution
  • Genetic interactions
  • Negative epistasis
  • Sign epistasis

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