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Evolution of digital organisms at high mutation rates leads to survival of the flattest


Darwinian evolution favours genotypes with high replication rates, a process called ‘survival of the fittest’. However, knowing the replication rate of each individual genotype may not suffice to predict the eventual survivor, even in an asexual population. According to quasi-species theory, selection favours the cloud of genotypes, interconnected by mutation, whose average replication rate is highest1,2,3,4,5. Here we confirm this prediction using digital organisms that self-replicate, mutate and evolve6,7,8,9. Forty pairs of populations were derived from 40 different ancestors in identical selective environments, except that one of each pair experienced a 4-fold higher mutation rate. In 12 cases, the dominant genotype that evolved at the lower mutation rate achieved a replication rate >1.5-fold faster than its counterpart. We allowed each of these disparate pairs to compete across a range of mutation rates. In each case, as mutation rate was increased, the outcome of competition switched to favour the genotype with the lower replication rate. These genotypes, although they occupied lower fitness peaks, were located in flatter regions of the fitness surface and were therefore more robust with respect to mutations.

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Figure 1: Competitions for one pair of organisms at four different mutation rates.
Figure 2: Genotype distributions after 15 generations from populations seeded uniformly with either A or B.
Figure 3: Critical mutation rates obtained from competition experiments versus predicted estimates based on each organism's intrinsic replication rate, w0, and mutational robustness parameters, a and b.


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This work was supported by the National Science Foundation. Part of this work as carried out at the Jet Propulsion Laboratory, under a contract with the National Aeronautics and Space Administration. J.L.W. acknowledges the support of an Axline SURF fellowship.

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Correspondence to Claus O. Wilke.

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Wilke, C., Wang, J., Ofria, C. et al. Evolution of digital organisms at high mutation rates leads to survival of the flattest. Nature 412, 331–333 (2001).

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