High-resolution genome-wide dissection of the two rules of speciation in Drosophila

Postzygotic reproductive isolation is characterized by two striking empirical patterns. The first is Haldane's rule—the preferential inviability or sterility of species hybrids of the heterogametic (XY) sex. The second is the so-called large X effect—substitution of one species's X chromosome for another's has a disproportionately large effect on hybrid fitness compared to similar substitution of an autosome. Although the first rule has been well-established, the second rule remains controversial. Here, we dissect the genetic causes of these two rules using a genome-wide introgression analysis of Drosophila mauritiana chromosome segments in an otherwise D. sechellia genetic background. We find that recessive hybrid incompatibilities outnumber dominant ones and that hybrid male steriles outnumber all other types of incompatibility, consistent with the dominance and faster-male theories of Haldane's rule, respectively. We also find that, although X-linked and autosomal introgressions are of similar size, most X-linked introgressions cause hybrid male sterility (60%) whereas few autosomal introgressions do (18%). Our results thus confirm the large X effect and identify its proximate cause: incompatibilities causing hybrid male sterility have a higher density on the X chromosome than on the autosomes. We evaluate several hypotheses for the evolutionary cause of this excess of X-linked hybrid male sterility.
Author Summary The evolution of reproductive isolation is a fundamental step in the origin of species. One kind of reproductive isolation, the sterility and inviability of species hybrids, is characterized by two of the strongest rules in evolutionary biology. The first is Haldane's rule: for species crosses in which just one hybrid sex is sterile or inviable, it tends to be the sex defined by having a pair of dissimilar sex chromosomes (e.g., the “XY” of males in humans). The second rule is the large X effect: the X chromosome has a disproportionately large effect on hybrid fitness. We dissected the genetic causes of these two rules of speciation by replacing many small chromosomal segments of the fruit fly Drosophila sechellia with those of a closely related species, D. mauritiana. Together, these segments cover 70% of the genome. We found that virtually all segments causing hybrid sterility or inviability act recessively and that hybrid male sterility is by far the most common type of hybrid incompatibility, confirming two leading theories about the causes of Haldane's rule. We also found that X-linked segments are more likely to cause hybrid male sterility than similarly sized autosomal segments. These results show that the large X effect is caused by a higher density of hybrid incompatibilities on the X chromosome.
A genome-wide introgression analysis of Drosophila mauritiana chromosome segments in an otherwise D. sechellia genetic background confirms the large X effect, a cornerstone of speciation theory, and reveals its cause.