Academic journal article Genetics

Clonal Interference and the Periodic Selection of New Beneficial Mutations in Escherichia Coli

Academic journal article Genetics

Clonal Interference and the Periodic Selection of New Beneficial Mutations in Escherichia Coli

Article excerpt

ABSTRACT

The conventional model of adaptation in asexual populations implies sequential fixation of new beneficial mutations via rare selective sweeps that purge all variation and preserve the clonal genotype. However, in large populations multiple beneficial mutations may co-occur, causing competition among them, a phenomenon called "clonal interference." Clonal interference is thus expected to lead to longer fixation times and larger fitness effects of mutations that ultimately become fixed, as well as to a genetically more diverse population. Here, we study the significance of clonal interference in populations consisting of mixtures of differently marked wild-type and mutator strains of Escherichia coli that adapt to a minimal-glucose environment for 400 generations. We monitored marker frequencies during evolution and measured the competitive fitness of random clones from each marker state after evolution. The results demonstrate the presence of multiple beneficial mutations in these populations and slower and more erratic invasion of mutants than expected by the conventional model, showing the signature of clonal interference. We found that a consequence of clonal interference is that fitness estimates derived from invasion trajectories were less than half the magnitude of direct estimates from competition experiments, thus revealing fundamental problems with this fitness measure. These results force a reevaluation of the conventional model of periodic selection for asexual microbes.

THE conventional model of adaptation in asexual populations posits that rare high fitness clones become sequentially fixed via relatively rapid selective sweeps alternated by periods during which the population waits for the next beneficial mutation to arise. This model of "periodic selection" (ATWOOD et al. 1951a) enjoys a certain amount of empirical support and underlies much of the current theory of adaptation based on the convenient assumption of "strong-selection, weakmutation" (ORR 2005). Early experiments with microbes that led to the original description of periodic selection showed erratic "sawtooth" dynamics in the frequency of neutral mutations and were interpreted as resulting from the sequential occurrence of beneficial mutations sweeping through the population to fixation (NoviCK and SZILARD 1950; ATWOOD et al. 1951a,b). Later work confirmed these earlier findings (PAQUIN and ADAMS 1983) and emphasized that a consequence of the sequential selective sweeps is the continual purging of all genetic and phenotypic variation, leading to the preservation of the wild type (KoCH 1974; LEVIN 1981).

However, under some conditions (e.g., large populations, high mutation rates, novel environmental conditions) beneficial mutations may be sufficiently common that they co-occur in the population. In the absence of recombination, this may lead to competition between separate clones that each carry different beneficial mutations, a phenomenon called "clonal interference" (GERRISH and LENSKI 1998). Theoretical work has shown that clonal interference leads to increased fitness effects and longer fixation times of those beneficial mutations that ultimately win the competition (GERRISH and LENSKI 1998; GERRISH 2001; ROZEN et al. 2002; WILKE 2004). Empirical evidence of clonal interference has begun to accumulate over recent years (LENSKI et al. 1991; DE VISSER et al. 1999; MIRALLES et al. 1999; YEDID and BELL 2001; ROZEN et al. 2002; SHAVER et al. 2002; COLEGRAVE 2002), showing its potential significance for adaptation of asexual populations. However, most of the available evidence of clonal interference is inferential and indirect support is scarce.

Here we aim to find more direct evidence of clonal interference by studying the invasion of new beneficial mutations in evolving populations of Escherichia coli. Similar to the classical study by CHAO and Cox (1983), we allowed mixtures of two strains with different mutation rates (mut+ and mutS) at varying ratios to adapt to novel conditions for 400 generations while monitoring their ratio using a fixed neutral marker. …

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