Hybrid Incompatibility in Drosophila: An Updated Genetic and Evolutionary Analysis Antonio Fontdevila, Grup de Genòmica, Bioinformàtica i Biologia Evolutiva, Departament de Genètica i Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Spain Advanced article Article Contents • Introduction: The Pioneers • The Search for ‘Speciation Genes’ • The Rules of HI • Evolving Hybrid Incompatibilities • Coda: Final Remarks and Future Perspectives • Acknowledgements Online posting date: 15 th February 2016 Negative interactions between independently evolved genes in two species are responsible of incompatibility of their hybrid, manifested by sterility and inviability. The heterogametic sex (XY males in Drosophila) is the most affected and the X chromosome has the largest effect on hybrid incompatibility (HI). These rules of speciation depend on the genetic architecture of HI. Albeit some speciation genes have a major effect, this architecture shows a complex polygenic structure of multiple interactions. HI genes are frequently associated to genetic factors that evolved self- ishly by favouring their preferential transmission. Genetic analyses show signatures of positive selec- tion in speciation genes that may favour the role of adaptive evolution. Whether these signatures are compatible with evolution of selfish factors – an idea that is gaining support – still remains a contentious issue. Finally, there is also a current upsurge of evidences in favour of the importance of genetic regulation in the evolution of hybrid incompatibilities. Introduction: The Pioneers Darwin has often been criticised that, despite the title of his mag- num opus The origin of species, he never tackled the biological basis of this origin. This criticism is unfair because he not only devoted a whole chapter to this topic but also discussed in it the problem of hybrid sterility in relation to natural selection. His view was that hybrid sterility cannot arise by adaptation, but rather must be ‘incidental on other acquired differences’. Darwin eLS subject area: Cell Biology How to cite: Fontdevila, Antonio (February 2016) Hybrid Incompatibility in Drosophila: An Updated Genetic and Evolutionary Analysis. In: eLS. John Wiley & Sons, Ltd: Chichester. DOI: 10.1002/9780470015902.a0020896.pub2 also discussed the relative role of gene fow and adaptation in the origin of species, undermining the necessity of strong iso- lation in front of the action of natural selection in the origin of species, a view that is now being vindicated (see Fontdevila, 2011, Chapter 4, p. 116, for a detailed discussion). He also recog- nised several genetic facts of hybridisation, among them that sterility is the result ‘from the organisation (the hybrid genome, in modern parlance) having been disturbed by two organisations (genomes) having been compounded into one’. However, lacking a general knowledge of Mendelian inheritance at the time, Dar- win was not able to produce a solid theory on the genetic basis of hybrid incompatibility (HI). More than 50 years had to pass until the Morgan’s fy lab in Columbia University pioneered genetic studies of HI. How much divergence must two populations show to be considered different species still is a matter of controversy. However, intuitively, pop- ulation thinking requires that, regardless of what mechanism is at work, two species lineages must keep their differential genetic identity by avoiding the confating effect of introgression. Since the most ubiquitous mechanism of gene exchange, at least in sexual organisms, is sex, there can be no question that repro- ductive isolation occurred to the frst evolutionists as a mech- anism to keep species identity. Alfred Sturtevant and Theodo- sius Dobzhansky are credited for their visionary genetic exper- iments with hybrids between pairs of closely related Drosophila species: D. melanogaster–D. simulans by Sturtevant (1920) and D. pseudoobscura–D. persimilis by Dobzhansky (1936). Both found that genetic factors, rather than chromosomal incompat- ibilities to pair in meiosis, were responsible for HI. Crosses between D. melanogaster and D. simulans yield hybrids that are either sterile or inviable, and the incompatibility of hybrids is sex-specifc depending on the direction of the cross. This obser- vation and further crosses with fies modifed for their X chro- mosome content (e.g. XXY D. melanogaster females) prompted Sturtevant to posit that hybrid inviability was caused by factors on the X chromosome. Unfortunately, the inviability or sterility of these hybrids prevented introgression crosses to be followed up, and no further dissection of the genetic of HI could be performed. This diffculty could be overcome using crosses between the more closely related species pair D. pseudoobscura–D. persimilis, which produce fertile females and sterile males. Aware of this fact, Dobzhansky (1936) was able to map the hybrid sterility eLS © 2016, John Wiley & Sons, Ltd. www.els.net 1