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. 2012 Oct;29(10):3153-9.
doi: 10.1093/molbev/mss122. Epub 2012 Apr 23.

Competition between transposable elements and mutator genes in bacteria

Tamás Fehér  1 , Balázs Bogos, Orsolya Méhi, Gergely Fekete, Bálint Csörgo, Károly Kovács, György Pósfai, Balázs Papp, Laurence D Hurst, Csaba Pál
Affiliations

Competition between transposable elements and mutator genes in bacteria

Tamás Fehér et al. Mol Biol Evol. 2012 Oct.

Abstract

Although both genotypes with elevated mutation rate (mutators) and mobilization of insertion sequence (IS) elements have substantial impact on genome diversification, their potential interactions are unknown. Moreover, the evolutionary forces driving gradual accumulation of these elements are unclear: Do these elements spread in an initially transposon-free bacterial genome as they enable rapid adaptive evolution? To address these issues, we inserted an active IS1 element into a reduced Escherichia coli genome devoid of all other mobile DNA. Evolutionary laboratory experiments revealed that IS elements increase mutational supply and occasionally generate variants with especially large phenotypic effects. However, their impact on adaptive evolution is small compared with mismatch repair mutator alleles, and hence, the latter impede the spread of IS-carrying strains. Given their ubiquity in natural populations, such mutator alleles could limit early phase of IS element evolution in a new bacterial host. More generally, our work demonstrates the existence of an evolutionary conflict between mutation-promoting mechanisms.

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Figures

F<sc>IG</sc>. 1.
FIG. 1.
Activation modes of the Escherichia coli cryptic bgl operon. Genes are indicated by gray arrows. (A) In wild-type cells, transcription of the bgl operon is silenced by multiple mechanisms. First, the promoter region (−35 and −10 region) is directly silenced by a nearby AT-rich DNA silencer element. Second, two rho-independent transcriptional terminators (T1 and T2) interrupt ongoing transcription (at the beginning and at the end of bglG). (B) IS insertion (dark gray box) can displace the silencer element from the bgl promoter region (−35 and −10) and allows transcription of the BglG antiterminator protein. Due to efficient antitermination by BglG in the presence of salicin, the operon is transcribed (filled, black arrows). (C) Mutations changing the CAP-binding site (starred black box) allow strong catabolic activation during carbon starvation. In addition, there are also numerous known point mutations that can activate the bgl operon. For more details, see Hall (1998) and Moorthy and Mahadevan (2002).
F<sc>IG.</sc> 2.
FIG. 2.
Competing genotypes and experimental setup. (A) This study uses a series of competition experiments among IS-free and IS1-harboring Escherichia coli MDS42 strains to investigate the impact of IS elements on evolutionary adaptation. E. coli strain MDS42 lacks all mobile DNA elements from its genome. An active single copy of IS1 was inserted to MDS42 by P1 transduction. Mutator versions of the above strains were generated by deleting the MMR gene mutS. Competing strains were also labeled with inducible yellow (YFP) or cyan (CFP) fluorescent proteins by inserting the corresponding genes into the genome (for a complete list of strains, see supplementary table 1, Supplementary Material online). The constitutively expressed TetR repressor enables transcriptional control of fluorescent protein–coding genes. An additional chloramphenicol resistance marker (CAT) ensures the stability of fluorescent markers. (B) Competition experiments were carried out with a starting 1:1 ratio of two strains carrying the YFP or CFP genes, respectively. Unless otherwise indicated in the main text, the first phase of the competition experiments involved long-term culturing of the mixed population in a medium that contains salicin as the sole carbon source. Small amounts of evolved cultures were transferred into fresh salicin-minimal medium containing inducer of fluorescent protein expression. The ratios of the two strains were inferred from the measured fluorescence intensities.
F<sc>IG</sc>. 3.
FIG. 3.
Outcome of competition experiments. Summary of competition experiments. Each arrow indicates the result of a competition experiment. Arrows point toward the genotypes with a higher probability of fixation in the populations, while the numbers above the arrows represent the ratios of the outcomes of parallel evolved populations. As can be seen on the figure, both IS carrying (IS+) and mutator (ΔmutS) genotypes outcompete MDS42 (χ2 = 39.8 degrees of freedom [df] = 1, P < 10−4 and χ2 = 454 df = 1, P << 10−4, respectively). Moreover, direct competition between IS+ and ΔmutS showed a higher selection of the latter (χ2 = 7.8 df = 1, P = 0.005). Remarkably, when competing genotypes have high underlying mutation rates (ΔmutS), selection of IS+ over IS− is significantly reduced (χ2 = 32.6 df = 1, P << 10−4): genotypes can fix in ∼61% of the adapted populations. Similarly, when both genotypes contain an IS element (ΔmutS IS+ vs. IS+), spread of ΔmutS mutator in the population is significantly lower compared with that in populations with IS-free genotypes (χ2 = 271 df = 1, P << 10−4). For more details on the outcome of competition experiments, see supplementary table 2 (Supplementary Material online).
F<sc>IG</sc>. 4.
FIG. 4.
Mutation rate and fitness measurements. (A) The figure shows mutation rates calculated from the numbers of colonies growing on salicin-minimal plates using fluctuation analyses. Bars indicate 95% confidence intervals. (B) Fitness of salicin-exploiting genotypes. We compared the growth characteristics of 37 strains where growth data were available and OD increment showed a coefficient of variation less than 0.2. Horizontal lines of the boxplots correspond to the medians, the bottoms and tops of the boxes show the 25th and 75th percentiles, respectively. Whiskers show either the maximum (minimum) value or 1.5 times the interquartile range of the data, whichever is smaller (higher). Points more than 1.5 times the interquartile range above the third quartile or below the first quartile are plotted individually as outliers. Difference of bgl+ IS-mutants compared with point mutants was highly significant (Wilcoxon rank-sum test, P < 10−4).
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