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

Abstract

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.

The impact of growth rate and environmental factors on mutation rates and spectra in Escherichia coli

“…In Fig. K, O and S, the three individual types of longer indel occurring in cycA (already described in (Maharjan and Ferenci, )) were less different to the unstressed state in the conditions studied than other types of mutations. SI mutations overall (Fig.…”

“…Mutation rates in cycA were estimated from the frequency of Cyc R generated from Cyc S in the presence () and absence () of oxygen at two different growth rates (0.6 and 0.1 h −1 ) as described in Methods. Mutation rate in cycA under nutrient unlimited (Un) obtained in (Maharjan and Ferenci, ) is also included showing the mutation rate under the unstressed exponential growth condition. Error bars are standard errors from at least six replicate experiments.…”

“…This currently presented data on growth rate effects provides further environmental settings to add to previously obtained mutational changes (Maharjan and Ferenci, ). With a total of 8 environmental settings, it is now possible to look at the breadth of changes to genetic variation in multiple environments.…”

No genome is an island: toward a 21st century agenda for evolution

“…Intriguingly, bacteria starved for different essential nutrients (carbon, nitrogen, oxygen, phosphorus, and iron) display significantly distinct qualitative spectra of mutational changes . The types of DNA changes affected differentially by nutrient deprivation include nucleotide substitutions, deletions, duplications, and insertions of mobile DNA elements.…”

Irregularities in genetic variation and mutation rates with environmental stresses

“…Nor, it seems, is there a uniform link between increased stress always leading to increased mutation rate. It is now clear that stressful environments can change mutation availability and mutation type in different ways (Maharjan and Ferenci, ; Maharjan and Ferenci, ). This conclusion was also reached recently with Saccharomyces cerevisiae (Liu and Zhang, ), indicating a complex relationship between environment, mutation rate and mutational bias.…”