Speciation occurs when genetic changes between individuals in two populations prevent them from mating or producing viable or fertile offspring. So far, few genes that are involved in these crucial differences between closely related species are known. Presgraves and colleagues have now identified one such gene that prevents successful reproduction between Drosophila melanogaster and its close relative Drosophila simulans. They show that natural selection was responsible for the changes that drove these two species apart, which provides fresh evidence in the debate about the forces behind speciation.

The authors identified a gene on chromosome 3 of D. simulans that is incompatible with an unknown gene or genes on the X chromosome of D. melanogaster. When the two species are crossed, the male offspring fail to survive — a phenomenon known as hybrid inviability. The authors mapped the D. simulans gene and identified it as Nup96–Nup98 , which encodes two proteins that are involved in the transfer of molecules between the nucleus and the cytoplasm. They found that it is the Nup96 protein that is responsible for the incompatibility with the D. melanogaster X chromosome.

But, have the crucial differences between the D. melanogaster and D. simulans versions of Nup96–Nup98 arisen as a result of natural selection or simply by chance? The authors compared the number of changes in the genes from the two species that led to amino-acid changes with those that did not affect the protein. They found a high proportion of changes that affect the composition of Nup96, which indicated that the divergence between the two genes was driven by selective pressure. To confirm and extend their results, the authors analysed the Nup96 sequence in African lines of D. melanogaster,  D. simulans and other Drosophila species. Again, their results indicated that the changes in Nup96 between D. melanogaster and D. simulans were the result of positive natural selection.

Together with an earlier study by Barbash et al., this is one of the first analyses to pinpoint the identity of a gene that is involved in reproductive incompatibility between closely related species. It will be exciting to identify the gene or genes on the X chromosome with which Nup96 interacts to cause male lethality, and to elucidate the molecular cause of the incompatibility between the two. It will also be interesting to see whether the strong evidence presented in this study that natural selection is involved in the genetic changes that contribute to speciation will be mirrored in other studies as more genes that are associated with hybrid inviability are identified.