The Integrity of the HMR complex is necessary for centromeric binding and reproductive isolation in Drosophila

Author summary A major cause of biological speciation is the sterility and/or lethality of hybrids. This hybrid lethality is thought to be the consequence of two incompatible genomes of the two different species. We used the fruit fly Drosophila melanogaster as a model system to isolate a defined protein complex, which mediates this hybrid lethality. Our data suggest that this complex containing six subunits has evolved in one Drosophila species (Drosophila melanogaster) to bring together components of centromeric and pericentromeric chromatin. We show that the integrity of the complex is necessary for its genomic binding patterns and its ability to maintain fertility in female Drosophila melanogaster flies. Hybrid males between Drosophila melanogaster and the very closely related species Drosophila simulans die because they contain elevated levels of this complex. These high levels result in mitotic defects and a misregulation in the expression of transposable elements in those hybrids. Our results show that mutations that interfere with the complex's function in Drosophila melanogaster also fail to induce lethality in hybrids suggesting that its evolutionary acquired functions in one species induce lethality in interspecies hybrids. Postzygotic isolation by genomic conflict is a major cause for the formation of species. Despite its importance, the molecular mechanisms that result in the lethality of interspecies hybrids are still largely unclear. The genus Drosophila, which contains over 1600 different species, is one of the best characterized model systems to study these questions. We showed in the past that the expression levels of the two hybrid incompatibility factors Hmr and Lhr diverged in the two closely related Drosophila species, D. melanogaster and D. simulans, resulting in an increased level of both proteins in interspecies hybrids. The overexpression of the two proteins also leads to mitotic defects, a misregulation in the expression of transposable elements and decreased fertility in pure species. In this work, we describe a distinct six subunit protein complex containing HMR and LHR and analyse the effect of Hmr mutations on complex integrity and function. Our experiments suggest that HMR needs to bring together components of centromeric and pericentromeric chromatin to fulfil its physiological function and to cause hybrid male lethality.

Automated summary

This study investigated the molecular mechanisms of hybrid lethality using the fruit fly Drosophila melanogaster as a model system, identifying a six subunit protein complex that plays a role in hybrid male lethality. Elevated levels of this complex in hybrid males lead to mitotic defects and misregulation of transposable elements.