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Distribution of fitness effects among beneficial mutations before selection in experimental populations of bacteria


The extent to which a population diverges from its ancestor through adaptive evolution depends on variation supplied by novel beneficial mutations. Extending earlier work1,2, recent theory makes two predictions that seem to be robust to biological details: the distribution of fitness effects among beneficial mutations before selection should be (i) exponential and (ii) invariant, meaning it is always exponential regardless of the fitness rank of the wild-type allele3,4. Here we test these predictions by assaying the fitness of 665 independently derived single-step mutations in the bacterium Pseudomonas fluorescens across a range of environments. We show that the distribution of fitness effects among beneficial mutations is indistinguishable from an exponential despite marked variation in the fitness rank of the wild type across environments. These results suggest that the initial step in adaptive evolution—the production of novel beneficial mutants from which selection sorts—is very general, being characterized by an approximately exponential distribution with many mutations of small effect and few of large effect. We also document substantial variation in the pleiotropic costs of antibiotic resistance, a result that may have implications for strategies aimed at eliminating resistant pathogens in animal and human populations.

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Figure 1: Frequency distributions of absolute fitness in selective (a) and permissive (b) environments.
Figure 2: Distribution of fitness effects among 18 beneficial mutants assayed in the permissive environment.
Figure 3: Observed (bars) and expected (dots) distribution of fitness effects among beneficial mutants assayed in (a) LB (fitness rank of wild type, 21); (b) glucose (fitness rank of wild type, 9); (c) mannitol (fitness rank of wild type, 15) and (d) sorbitol (fitness rank of wild-type, 26).
Figure 4: Mean fitness effects among beneficial mutants across environments in experiment 2.


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Thanks to M. Al-Azzabi and E. Drummond for technical assistance in the lab. S. Otto, S. Aris-Brossou, C. Zeyl, F.B. Christiansen and O.F. Christiansen provided comments. This work was supported by a Discovery Grant to R.K. from the Natural Sciences and Education Research Council of Canada.

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Correspondence to Rees Kassen.

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Kassen, R., Bataillon, T. Distribution of fitness effects among beneficial mutations before selection in experimental populations of bacteria. Nat Genet 38, 484–488 (2006).

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