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 model^{2, 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.

1. Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204–5001, USA
2. Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599–7575, USA
3. Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599–3280, USA

Correspondence to: Ricardo B. R. Azevedo¹ Correspondence and requests for materials should be addressed to R.B.R.A. (Email: razevedo@uh.edu).

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