Academic journal article Genetics

The Fitness Effects of Spontaneous Mutations Nearly Unseen by Selection in a Bacterium with Multiple Chromosomes

Academic journal article Genetics

The Fitness Effects of Spontaneous Mutations Nearly Unseen by Selection in a Bacterium with Multiple Chromosomes

Article excerpt

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THE extent to which spontaneous mutations contribute to evolutionary change largely depends on their rates and fitness effects. Both parameters are fundamental to several evolutionary problems, including the maintenance of genetic variation (Charlesworth et al. 1993, 2009; Charlesworth and Charlesworth 1998), the evolution of recombination (Muller 1964; Kondrashov 1988; Otto and Lenormand 2002; Roze and Blanckaert 2014), the evolution of mutator alleles (Sniegowski et al. 1997; Tenaillon et al. 1999), and deleterious mutation accumulation (MA) in small populations (Lande 1994; Lynch et al. 1995, 1999; Schwander and Crespi 2009). Many studies have now obtained direct and robust estimates of mutation rates and spectra across diverse organisms, but our understanding of the fitness effects of spontaneous mutations remains limited to mostly indirect estimates in classic model organisms (Eyre-Walker and Keightley 2007).

MA experiments provide the opportunity to quantify properties of the fitness of spontaneous mutations that have not been exposed to the sieve of natural selection. Specifically, MA experiments limit the efficiency of natural selection by passaging replicate lineages through repeated single-cell bottlenecks. These lineages accumulate mutations independently over several thousand generations, and the magnitude and variance in fitness between lineages can be used to estimate several properties of the distribution of fitness effects (Halligan and Keightley 2009). MA studies have been used to characterize the fitness effects of spontaneous mutations in Drosophila melanogaster (Bateman 1959; Mukai 1964; Keightley 1994; Fry etal. 1999), Arabidopsis thaliana (Schultz etal. 1999; Shaw etal. 2000, 2002), Caenorhabditis elegans (Keightley and Caballero 1997; Vassilieva et al. 2000; Estes et al. 2004; Katju et al. 2015), Saccharomyces cerevisiae (Wloch et al. 2001; Zeyl and de Visser 2001; Dickinson 2008; Jasmin and Lenormand 2015), Escherichia coli (Kibota and Lynch 1996; Trindade et al. 2010), and other microbes (Heilbron etal. 2014;Kraemer etal. 2015). Results from these studies have occasionally been inconsistent, but the majority of results suggest that most spontaneous mutations have mild effects (Eyre-Walker and Keightley 2007; Halligan and Keightley 2009; Agrawal and Whitlock 2012; Heilbron et al. 2014), that deleterious mutations far outnumber beneficial mutations (Keightley and Lynch 2003; Eyre-Walker and Keightley 2007; Silander et al. 2007), and that the distribution of effects of deleterious mutations is complex and multimodal (Zeyl and de Visser 2001; Eyre-Walker and Keightley 2007).

A more powerful approach for studying the fitness effects of spontaneous mutations is to pair MA experiments with wholegenome sequencing (MA-WGS), so that both the genetic basis and fitness effects of a collection of mutations can be known. MA-WGS studies have been conducted in a diverse array of bacteria, generating a growing database of naturally accumulated mutations that has dramatically improved estimates of mutation rates and spectra (Lee et al. 2012; Sung et al. 2012, 2015; Heilbron etal. 2014; Long etal. 2014, 2015; Dillon etal. 2015; Foster etal. 2015; Dettman etal. 2016). Yet, only one of these studies has also characterized the fitness of MA-WGS lines (Heilbron etal. 2014), and this study was conducted with mutator lineages, which have altered base substitution and indel biases and produce hundreds of mutations per line (Lee et al. 2012; Sung et al. 2015). Our understanding of the fitness effects of spontaneous mutations would benefit greatly from more direct estimates of fitness derived from MA lineages that harbor fewer known mutations.

Here, we measured the relative fitness of 43 fully sequenced MA lineages derived from Burkholderia cenocepacia HI2424 in three laboratory environments after they had been evolved in the near absence of natural selection for 5554 generations. …

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