Figure 1. The timeline of putative selective events at two loci with alleles refractory to sigma virus infection. At the ref(3)D locus, a selective sweep occurred between 25 and 240 years ago (indicated in green), reducing the frequency of the susceptible A allele (shown in blue) and increasing the frequency of the resistant B allele (yellow) to over 80%. The first unique features of the B allele have been dated to 90,000 years ago. The highly resistant C allele (red) is present in only one of the lines tested. At the ref(2)P locus, the GLU-ASP resistance allele is present at about 20% frequency in some contemporary populations, and is believed to have arisen 1,000–7,000 years ago. doi:10.1371/journal.pgen.1002347.g001 that case, it is not that the organism starts multiple steps away from the ‘‘adaptive peak’’, but that after each step, the ‘‘adaptive landscape’’ changes. Magwire et al. [3] suggest that the adaptive response to the sigma virus has pre-adapted D. melanogaster to OP insecti- cides. However, it is now unclear how References 1. Schmidt JM, Good RT, Appleton B, Sherrard J, Raymant GC, et al. (2010) Copy number variation and transposable elements feature in recent, ongoing adaptation at the Cyp6g1 locus. PLoS Genet 6: e1000998. doi:10.1371/journal. pgen.1000998. 2. Raymond M, Berticat C, Weill M, Pasteur N, Chevillon C (2001) Insecticide resistance in the mosquito Culex pipiens: what have we learned about adaptation? Genetica 112–113: 287–296. 3. Magwire MM, Bayer F, Webster CL, Cao C, Jiggins FM (2011) Successive increases in the resistance of Drosophila to viral infection through a transposon insertion followed by a duplication. PLoS Genet 7: e1002337. doi:10.1371/journal. pgen.1002337. 4. Rogers RL, Bedford T, Lyons AM, Hartl DL (2010) Adaptive impact of the chimeric gene Quetzalcoatl in Drosophila melanogaster. Proc Natl Acad Sci U S A 107: 10943–10948. 5. Long M, Betran E, Thornton K, Wang W (2003) The origin of new genes: Glimpses from the young and old. Nat Rev Genet 4: 865–875. 6. Aminetzach YT, Macpherson JM, Petrov DA (2005) Pesticide resistance via transposition-me- diated adaptive gene truncation in Drosophila. Science 309: 764–767. important OPs have been to selection at this locus. One of the mysteries about the DOC element insertion into the CHKov1 gene is that the age of the allele (estimated to be ,90,000 years), as determined by its divergence from the ancestral allele, is much older than the use of insecticides and the age of the selective sweep, which was determined from the patterns in nearby polymorphisms. The presence/ absence of the DOC insertion is also correlated with the presence/absence of seven amino acid changes affecting a predicted protein that is substantially shortened and altered relative to that encoded by the ancestral allele. Now we know of another selective agent, namely the sigma virus, that is thought to have been infecting D. melanogaster for at least 200 years, but probably longer [9]. A highly virulent variant of the sigma virus is thought to have spread through European Drosophila populations in the 1980s, and that is possibly responsible for the recent sweep [10]. Magwire et al.’s [3] findings should motivate molecular and biochemical investi- gations of the various alleles of CHKov1 and 2, and of the somewhat mysterious group of paralogous proteins currently dubbed ‘‘cho- line kinase–like’’. Finally, such examples of allelic series not only tell us about population size and structure, but also provide important empirical examples of how fast adaptive evolution at a single locus can be, and should motivate the search for other ‘‘adaptive allelic series’’ that will help us understand the limits and dynamics of adaptation. 7. Gay P (1978) Drosophila genes which intervene in multiplication of sigma virus. Mol Gen Genet 159: 269–283. 8. Bangham J, Obbard DJ, Kim K-W, Haddrill PR, Jiggins FM (2007) The age and evolution of an antiviral resistance mutation in Drosophila melano- gaster. P R Soc B 274: 2027–2034. 9. Carpenter JA, Obbard DJ, Maside X, Jiggins FM (2007) The recent spread of a vertically transmit- ted virus through populations of Drosophila melanogaster. Mol Ecol 16: 3947–3954. 10. Fleuriet A, Sperlich D (1992) Evolution of the Drosophila melanogaster-sigma virus system in a natural population from Tu¨bingen. Theor Appl Genet 85: 186–189. PLoS Genetics | www.plosgenetics.org 2 October 2011 | Volume 7 | Issue 10 | e1002347