The Hybrid Incompatibility Genes <i>Lhr</i> and <i>Hmr</i> Are Required for Sister Chromatid Detachment During Anaphase but Not for Centromere Function

Abstract

Crosses between <i>Drosophila melanogaster</i> females and <i>Drosophila simulans</i> males produce hybrid sons that die at the larval stage. This hybrid lethality is suppressed by loss-of-function mutations in the <i>D. melanogaster Hybrid male rescue</i> (<i>Hmr</i>) or in the <i>D. simulans Lethal hybrid rescue</i> (<i>Lhr</i>) genes. Previous studies have shown that Hmr and Lhr interact with heterochromatin proteins and suppress expression of transposable elements within <i>D. melanogaster</i> It also has been proposed that Hmr and Lhr function at the centromere. We examined mitotic divisions in larval brains from <i>Hmr</i> and <i>Lhr</i> single mutants and <i>Hmr</i>; <i>Lhr</i> double mutants in <i>D. melanogaster</i> In none of the mutants did we observe defects in metaphase chromosome alignment or hyperploid cells, which are hallmarks of centromere or kinetochore dysfunction. In addition, we found that Hmr-HA and Lhr-HA do not colocalize with centromeres either during interphase or mitotic division. However, all mutants displayed anaphase bridges and chromosome aberrations resulting from the breakage of these bridges, predominantly at the euchromatin-heterochromatin junction. The few dividing cells present in hybrid males showed fuzzy and irregularly condensed chromosomes with unresolved sister chromatids. Despite this defect in condensation, chromosomes in hybrids managed to align on the metaphase plate and undergo anaphase. We conclude that there is no evidence for a centromeric function of Hmr and Lhr within <i>D. melanogaster</i> nor for a centromere defect causing hybrid lethality. Instead, we find that <i>Hmr</i> and <i>Lhr</i> are required in <i>D. melanogaster</i> for detachment of sister chromatids during anaphase.