Date Published: November 14, 2013
Publisher: Public Library of Science
Author(s): Daniel J. P. Engelmoer, Ian Donaldson, Daniel E. Rozen, Dan Dykhuizen.
Natural transformation has significant effects on bacterial genome evolution, but the evolutionary factors maintaining this mode of bacterial sex remain uncertain. Transformation is hypothesized to have both positive and negative evolutionary effects on bacteria. It can facilitate adaptation by combining beneficial mutations into a single individual, or reduce the mutational load by exposing deleterious alleles to natural selection. Alternatively, it may expose transformed cells to damaged or otherwise mutated environmental DNA and is energetically expensive. Here, we examine the long-term effects of transformation in the naturally competent species Streptococcus pneumoniae by evolving populations of wild-type and competence-deficient strains in chemostats for 1000 generations. Half of these populations were exposed to periodic mild stress to examine context-dependent benefits of transformation. We find that competence reduces fitness gain under benign conditions; however, these costs are reduced in the presence of periodic stress. Using whole genome re-sequencing, we show that competent populations fix fewer new mutations and that competence prevents the emergence of mutators. Our results show that during evolution in benign conditions competence helps maintain genome stability but is evolutionary costly; however, during periods of stress this same conservativism enables cells to retain fitness in the face of new mutations, showing for the first time that the benefits of transformation are context dependent.
Natural transformation is an important cause of genome evolution in bacteria, but the evolutionary factors maintaining natural transformation, or competence, in bacteria remain uncertain , , , . Transformation is widely believed to have evolved to facilitate adaptation, especially in a clinical context where transformation occurs at a high rate and may allow pathogens to evade antibiotics or immune surveillance , , , . However, transformation can both be beneficial and costly to bacterial cells. It can speed up adaptation by combining non-antagonistically epistatic beneficial mutations into a single individual , , , , similar to the Fisher-Muller effect in Eukaryotes. It can also reduce the mutation load by combining deleterious alleles into a common background, which more efficiently exposes these mutations to natural selection , , , . Similarly, transformation can eliminate deleterious alleles if these are replaced by transformed DNA with the wild-type sequence . Such a function has been inferred in naturally transforming Neisseria, where high rates of transformation with ‘self-DNA’ leads to conservation of core regions of the genome . Alternatively, transformation can impose significant fitness costs because it is energetically expensive and bacterial cells may incorporate damaged or mutated environmental DNA that reduces bacterial fitness . Thus, although the mechanisms that regulate bacterial transformation are well understood, the evolutionary factors that maintain this process are not.
Transformation can dramatically benefit S. pneumoniae by facilitating the evolution of drug resistance and the emergence of novel modes of virulence , , . However, these benefits in pathogenic bacterial lineages under strong antibiotic selection tell only part of the story, and may not reflect the effects of transformation more broadly. Using an experimental evolution approach, we found that competence benefited cells by reducing the mutation load and limiting the emergence of mutators (Fig. 2). Additionally, competent populations reached higher fitness when evolving in the presence of periodic stress; equally, exposure to periodic stress decreased the rate of evolution of non-competent populations (Fig. 1). Although we applied an extremely mild stress in our experiment (Figure S1), it is notable that the kanamycin concentration we used is sufficient to induce competence in wild-type strains . It is therefore possible that benefits to competence in populations that experienced drug-stress was the result of increased recombination, which could have off-set the cost of transformation in a benign environment by slightly increasing their rate of adaptation. By contrast, non-competent cells exposed to kanamycin may face greater costs because kanamycin causes an inability to repair ribosomal decoding errors, which can subsequently lead to DNA damage and increase the mutation rate . These stress-dependent benefits of competence may be particularly important in the human nasopharynx, where S. pneumoniae is exposed to unpredictable and severe stress from drug exposure, immune surveillance and from coexisting bacterial competitors.