The hybrid incompatibility gene Lhr represses repetitive elements. Satyaki P. Rajavasireddy, Shuqing Ji, Daniel A Barbash. Molecular Biology and Genetics, Cornell University, Ithaca, NY.

   Heterochromatin keeps in check selfish elements such as transposable elements and satellites that will otherwise increase their copy number and potentially reduce host fitness. These selfish elements have been proposed to be in a continuous arms race with heterochromatin proteins, driving their sequence divergence and causing interspecific hybrid incompatibility (HI). However, direct evidence linking HI with genetic conflicts between selfish DNA and heterochromatin is limited. Lhr encodes a rapidly evolving, HP1a interacting, heterochromatin protein that causes hybrid lethality between D. melanogaster and D. simulans. To determine whether Lhr evolved to suppress genetic conflicts requires understanding its intraspecific function . We therefore knocked-out Lhr via homologous recombination in D. melanogaster and discovered that Lhr mutant (Lhr^KO) females have reduced fertility. mRNA-seq analysis shows that Lhr loss leads to widespread increase in the abundance of transcripts from transposable elements (TEs) and satellite DNAs but has little effect on protein-coding genes. ChIP and reporter gene studies suggest that this increased abundance of TE transcripts is due to a defect in post-transcriptional TE repression. We further found that Lhr^KO flies have long telomeres, which we propose is due to derepression of telomeric TEs as well as to LHR protein being required at the telomere cap in the wild type. We have also performed an RNA-seq analysis of a D. simulans Lhr mutant strain, providing a rare opportunity to compare the function of an adaptively evolving heterochromatin protein between two species. We are currently analyzing these data to determine if the Lhr-dependent regulation of specific TEs or satellite DNAs has changed between D. melanogaster and D. simulans. Our data strongly suggest that selfish elements are a direct selection pressure driving the divergence of Lhr and are thus consistent with the arms race model.