Gap genes are involved in inviability in hybrids between Drosophila melanogaster and D. santomea

Evolved changes within species lead to the inevitable loss of viability in hybrids. Inviability is also a convenient phenotype to genetically map and validate functionally divergent genes and pathways differentiating closely related species. Here we identify the Drosophila melanogaster form of the highly conserved essential gap gene giant (gt) as a key genetic determinant of hybrid inviability in crosses with D. santomea. We show that the coding region of this allele in D. melanogaster/D. santomea hybrids is sufficient to cause embryonic inviability not seen in either pure species. Further genetic analysis indicates that tailless (tll), another gap gene, is also involved in the hybrid defects. giant and tll are both members of the gap gene network of transcription factors that participate in establishing anterior-posterior specification of the dipteran embryo, a highly conserved developmental process. Genes whose outputs in this process are functionally conserved nevertheless evolve over short timescales to cause inviability in hybrids.