Competition between high- and higher-mutating strains ofEscherichia coli

Abstract

Experimental studies have shown that a mutator allele can readily hitchhike to fixation with beneficial mutations in an asexual population having a low, wild-type mutation rate. Here, we show that a genotype bearing two mutator alleles can supplant a population already fixed for one mutator allele. Our results provide experimental support for recent theory predicting that mutator alleles will tend to accumulate in asexual populations by hitchhiking with beneficial mutations, causing an ever-higher genomic mutation rate.

Experimental evolution and the dynamics of genomic mutation rate modifiers

“…Alternatively, if beneficial mutations are so frequent that they co-occur in a population, then competition between mutator and wild-type lineages carrying beneficial mutations (Gerrish and Lenski, 1998;Wilke, 2004;Sniegowski and Gerrish, 2010) may also interfere with mutator hitchhiking. Mutator dynamics characterized by non-monotonic and slower-than-expected changes in frequency are consistent with the effect of such 'clonal interference' from the wild-type subpopulation and have been observed in multiple experimental studies in both bacteria and yeast (Shaver et al, 2002;de Visser and Rozen, 2006;Gentile et al, 2011;Raynes et al, 2012); clonal interference effects on mutator hitchhiking have also been shown to strengthen with increasing population size as a result of higher overall beneficial mutation supply rate (Raynes et al, 2012). Mutator hitchhiking dynamics are also expected to depend on the distribution of fitness effects of new mutations.…”

“…Such experiments have primarily been performed in vitro in E. coli (Trobner and Piechocki, 1984a;Labat et al, 2005;de Visser and Rozen, 2006;Loh et al, 2010;Gentile et al, 2011) and the yeast Saccharomyces cerevisiae (Thompson et al, 2006;Raynes et al, 2011Raynes et al, , 2012Raynes et al, , 2014, but some work has also been carried out in vivo by propagating E. coli populations in the mouse gut (Giraud et al, 2001). The focus of these experiments has not necessarily been to demonstrate mutator hitchhiking anew, but rather to explore the influence of various population genetic factors on the likelihood and dynamics of mutator hitchhiking, as discussed below.…”

“…To date, there has been only one experimental test related to this idea: Gentile et al (2011) used Chao and Cox-style competition experiments to show that a strain of E. coli bearing two mutator alleles (mismatch repair and proofreading deficiencies) can prevail over an isogenic strain bearing a single mutator allele and having a correspondingly lower mutation rate. These results are consistent with the theory that mutation rate evolution is upwardly biased in asexual populations undergoing adaptive evolution; whether spontaneously originated multiple mutator genotypes can evolve by hitchhiking, however, has yet to be investigated experimentally.…”

“…Theoretical studies began exploring the population genetics of mutation rate modifier alleles in the 1960s, and significant theory papers on mutation rate evolution have appeared in every decade since (Kimura, 1967;Leigh, 1970Leigh, , 1973Ishii et al, 1989;Taddei et al, 1997;Johnson, 1999;Andre and Godelle, 2006;Gerrish et al, 2007;Lynch, 2008;Wylie et al, 2009;Desai and Fisher, 2011). Direct experimental work on the population genetics of mutation rate modifiers began in the 1970s (Gibson et al, 1970;Cox and Gibson, 1974) and has grown rapidly in recent years (Giraud et al, 2001;Notley-McRobb et al, 2002b;Thompson et al, 2006;Pal et al, 2007;Gentile et al, 2011;Raynes et al, 2011Raynes et al, , 2012Raynes et al, , 2014McDonald et al, 2012;Maharjan et al, 2013;Wielgoss et al, 2013). Here, we review advances in our understanding of mutation rate evolution that have been contributed by experimental studies.…”

Experiments, Simulations, and Epistemic Privilege

“…Experimental evolution commonly uses bacteria as objects of study. They are ideal for a number of reasons: They have short generation times, large populations can be kept in very small spaces, and they can be frozen and revived, allowing for comparisons and competitions between evolved populations and their ancestors (Gentile et al 2011;Lenski et al 1991). 6 A notable example is Richard Lenski's long-term evolution experiment.…”