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Sexual reproduction selects for robustness and negative epistasis in artificial gene networks

A Corrigendum to this article was published on 05 October 2006


The mutational deterministic hypothesis for the origin and maintenance of sexual reproduction posits that sex enhances the ability of natural selection to purge deleterious mutations after recombination brings them together into single genomes1. This explanation requires negative epistasis, a type of genetic interaction where mutations are more harmful in combination than expected from their separate effects. The conceptual appeal of the mutational deterministic hypothesis has been offset by our inability to identify the mechanistic and evolutionary bases of negative epistasis. Here we show that negative epistasis can evolve as a consequence of sexual reproduction itself. Using an artificial gene network model2,3, we find that recombination between gene networks imposes selection for genetic robustness, and that negative epistasis evolves as a by-product of this selection. Our results suggest that sexual reproduction selects for conditions that favour its own maintenance, a case of evolution forging its own path.

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Figure 1: Types of directional epistasis for deleterious mutations.
Figure 2: Application of our network model to the gap gene system of Drosophila melanogaster.
Figure 3: Sexual reproduction selects for mutational robustness and negative epistasis.


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We thank T. Flatt, Y. Fofanov, F. Galis, J. Kingsolver, A. Monteiro, M. Travisano and G. Wagner for discussions. The UH, UNC and NIH (grant to C.L.B.) provided financial support.

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Correspondence to Ricardo B. R. Azevedo.

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Supplementary Notes

This file was replaced on 5 October 2006. See Corrigendum to original paper. (PDF 284 kb)

This file contains Supplementary Methods, Supplementary Figures and their legends, and respective additional references. The Supplementary Methods contain a list of default network and population genetic parameters, methods for the experiments described in Fig. 3b (main text), details of the software used, and methods for the experiments reported in the Supplementary Figures. The Supplementary Figures show sensitivity analyses of the evolutionary responses in robustness and directional epistasis to changes in various network and population genetic parameters (Supplementary Figures 1, 4–9), estimates of the initial recombination load in the experiments described in Fig. 3b (main text) (Supplementary Figure 2), and the correlation between genetic robustness and directional epistasis in random networks (Supplementary Figure 3).

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Azevedo, R., Lohaus, R., Srinivasan, S. et al. Sexual reproduction selects for robustness and negative epistasis in artificial gene networks. Nature 440, 87–90 (2006).

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