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The role of epistasis in shaping genetic variation and contributing to observable differences within and between populations has been the focus of much debate (1-3). In complex trait genetics, the [...], The importance of epistasis--non-additive interactions between alleles--in shaping population fitness has long been a controversial topic, hampered in part by lack of empirical evidence (1-4). Traditionally, epistasis is inferred on the basis of non-independence of genotypic values between loci for a given trait. However, epistasis for fitness should also have a genomic footprint (5-7). To capture this signal, we have developed a simple approach that relies on detecting genotype ratio distortion as a sign of epistasis, and we apply this method to a large panel of Drosophila melanogaster recombinant inbred lines (8,9). Here we confirm experimentally that instances of genotype ratio distortion represent loci with epistatic fitness effects; we conservatively estimate that any two haploid genomes in this study are expected to harbour 1.15 pairs of epistatically interacting alleles. This observation has important implications for speciation genetics, as it indicates that the raw material to drive reproductive isolation is segregating contemporaneously within species and does not necessarily require, as proposed by the Dobzhansky-Muller model, the emergence of incompatible mutations independently derived and fixed in allopatry. The relevance of our result extends beyond speciation, as it demonstrates that epistasis is widespread but that it may of ten go undetected owing to lack of statistical power or lack of genome-wide scope of the experiments. A C G A C G

Author(s): Gibran Hemani [sup.1] [sup.2] , Konstantin Shakhbazov [sup.1] [sup.2] , Harm-Jan Westra [sup.3] , Tonu Esko [sup.4] [sup.5] [sup.6] , Anjali K. Henders [sup.7] , Allan F. McRae [sup.1] [...]

The main forces directing long-term molecular evolution remain obscure. A sizable fraction of amino-acid substitutions seem to be fixed by positive selection (1-4), but it is unclear to what degree [...]

REPLYING TO D. M. McCandlish, E. Rajon, P. Shah, Y. Ding&J. B. Plotkin Nature 497, http://dx.doi.org/10.1038/nature12219 (2013) Understanding fitness landscapes, a conceptual depiction of the genotype-to-phenotype relationship, is crucial to [...]

ARISING FROM M. S. Breen, C. Kemena, P. K. Vlasov, C. Notredame & F. A. Kondrashov Nature 490, 535-538 (2012) An important question in molecular evolution is whether an amino [...]

There is a long-standing controversy in evolutionary biology about the relative importance of 'internal' versus 'external' factors in determining the rate and outcomes of evolution. Is evolution primarily determined by [...]

If you cross two black guinea pigs you may get several albino pups. This could happen, for example, if the boar and sow are both heterozygous at the C locus [...]