Fitness decline in spontaneous mutation accumulation lines of<i>Caenorhabditis elegans</i>with varying effective population sizes

Katju, Vaishali; Packard, Lucille B.; Bu, Lijing; Keightley, Peter D.; Bergthorsson, Ulfar

doi:10.1111/evo.12554

Cited by 44 publications

(96 citation statements)

References 51 publications

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“…Indeed, we found that nearly all the variation in fitness among segregants from diploid and haploid lines was explained by one or two large-effect mutations, which implies that variance in fitness among lines is largely due to variance in mutational effects. This is expected when lines are propagated for a short period of time (Wloch et al 2001) but is perhaps more surprising in long-term lines such as Dickinson's [although for similar results, see also Caballero et al (2002), Halligan et al (2003), Estes et al (2004), Heilbron et al (2014), and Katju et al (2015)]. …”

Section: Discussionmentioning

confidence: 74%

Accelerating Mutational Load Is Not Due to Synergistic Epistasis or Mutator Alleles in Mutation Accumulation Lines of Yeast

Jasmin

Lenormand

2015

Genetics

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Much of our knowledge about the fitness effects of new mutations has been gained from mutation accumulation (MA) experiments. Yet the fitness effect of single mutations is rarely measured in MA experiments. This raises several issues, notably for inferring epistasis for fitness. The acceleration of fitness decline in MA lines has been taken as evidence for synergistic epistasis, but establishing the role of epistasis requires measuring the fitness of genotypes carrying known numbers of mutations. Otherwise, accelerating fitness loss could be explained by increased genetic mutation rates. Here we segregated mutations accumulated over 4800 generations in haploid and diploid MA lines of the yeast Saccharomyces cerevisiae. We found no correspondence between an accelerated fitness decline and synergistic epistasis among deleterious mutations in haploid lines. Pairs of mutations showed no overall epistasis. Furthermore, several lines of evidence indicate that genetic mutation rates did not increase in the MA lines. Crucially, segregant fitness analyses revealed that MA accelerated in both haploid and diploid lines, even though the fitness of diploid lines was nearly constant during the MA experiment. This suggests that the accelerated fitness decline in haploids was caused by cryptic environmental factors that increased mutation rates in all lines during the last third of the lines' transfers. In addition, we provide new estimates of deleterious mutation rates, including lethal mutations, and highlight that nearly all the mutational load we observed was due to one or two mutations having a large effect on fitness.

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Section: Discussionmentioning

confidence: 74%

Accelerating Mutational Load Is Not Due to Synergistic Epistasis or Mutator Alleles in Mutation Accumulation Lines of Yeast

Jasmin

Lenormand

2015

Genetics

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“…Although worms cannot match the short generation times or large population sizes of microbes such as yeast or bacteria commonly employed for EE ( b ell 1997; k assen 2014), relatively long-term evolution is feasible with C. elegans ; e.g. , lineages have been cultured under selfing for up to 400 generations ( m atsuba et al 2012; k atju et al 2015), and maintained under different reproductive systems for up to 200 generations ( t heologidis et al 2014). …”

Section: What Is Experimental Evolution?mentioning

confidence: 99%

“…Left, illustration of how an MA experiment is performed, adapted from Halligan and Keightley (2009) and Katju et al (2015). G indicates the generation of EE, N the number of individuals allowed to reproduce within each MA line, and n the number of MA lines.…”

Section: Goals Outcomes and Interpretation Of Experimental Evolutionmentioning

confidence: 99%

Experimental Evolution withCaenorhabditisNematodes

et al. 2017

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The hermaphroditic nematode Caenorhabditis elegans has been one of the primary model systems in biology since the 1970s, but only within the last two decades has this nematode also become a useful model for experimental evolution. Here, we outline the goals and major foci of experimental evolution with C. elegans and related species, such as C. briggsae and C. remanei, by discussing the principles of experimental design, and highlighting the strengths and limitations of Caenorhabditis as model systems. We then review three exemplars of Caenorhabditis experimental evolution studies, underlining representative evolution experiments that have addressed the: (1) maintenance of genetic variation; (2) role of natural selection during transitions from outcrossing to selfing, as well as the maintenance of mixed breeding modes during evolution; and (3) evolution of phenotypic plasticity and its role in adaptation to variable environments, including host–pathogen coevolution. We conclude by suggesting some future directions for which experimental evolution with Caenorhabditis would be particularly informative.

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“…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 et al 1999), Arabidopsis thaliana Shaw et al 2000Shaw et al , 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 et al 2014;Kraemer et al 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).…”

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confidence: 99%

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

Dillon

Cooper

2016

Genetics

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Mutation accumulation (MA) experiments employ the strategy of minimizing the population size of evolving lineages to greatly reduce effects of selection on newly arising mutations. Thus, most mutations fix within MA lines independently of their fitness effects. This approach, more recently combined with genome sequencing, has detailed the rates, spectra, and biases of different mutational processes. However, a quantitative understanding of the fitness effects of mutations virtually unseen by selection has remained an untapped opportunity. Here, we analyzed the fitness of 43 sequenced MA lines of the multi-chromosome bacterium Burkholderia cenocepacia that had each undergone 5554 generations of MA and accumulated an average of 6.73 spontaneous mutations. Most lineages exhibited either neutral or deleterious fitness in three different environments in comparison with their common ancestor. The only mutational class that was significantly overrepresented in lineages with reduced fitness was the loss of the plasmid, though nonsense mutations, missense mutations, and coding insertion-deletions were also overrepresented in MA lineages whose fitness had significantly declined. Although the overall distribution of fitness effects was similar between the three environments, the magnitude and even the sign of the fitness of a number of lineages changed with the environment, demonstrating that the fitness of some genotypes was environmentally dependent. These results present an unprecedented picture of the fitness effects of spontaneous mutations in a bacterium with multiple chromosomes and provide greater quantitative support for the theory that the vast majority of spontaneous mutations are neutral or deleterious.KEYWORDS fitness effects; deleterious mutation; pleiotropy; genetic drift; Burkholderia cenocepacia T HE 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(Charlesworth et al. , 2009Charlesworth 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. 1995Lynch et al. , 1999Schwander 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 throu...

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Fitness decline in spontaneous mutation accumulation lines ofCaenorhabditis eleganswith varying effective population sizes

Cited by 44 publications

References 51 publications

Accelerating Mutational Load Is Not Due to Synergistic Epistasis or Mutator Alleles in Mutation Accumulation Lines of Yeast

Accelerating Mutational Load Is Not Due to Synergistic Epistasis or Mutator Alleles in Mutation Accumulation Lines of Yeast

Experimental Evolution withCaenorhabditisNematodes

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

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