Can a genomic arms race drive the development of reproductive barriers between species? The story of Lhr

Genomic parasites such as transposable elements and satellites that can increase their copy number and potentially reduce host fitness are held in check by heterochromatin - a repressive nuclear compartment. These selfish elements have been proposed to be in a continuous arms race with heterochromatin proteins, driving their sequence divergence and leading to the formation of reproductive barriers between species. However, direct evidence linking such reproductive barriers with genetic conflicts between selfish DNA and heterochromatin is limited. Lhr encodes a rapidly evolving heterochromatin protein that causes lethality among the hybrid progeny of D. melanogaster and D. simulans. To determine whether Lhr’s sequence is changing to suppress genetic conflicts requires understanding its function within Drosophila species. We therefore knocked-out Lhr via homologous recombination in D. melanogaster and discovered that Lhr mutant females have reduced fertility. mRNA-seqanalysis shows that Lhr loss leads to a 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 also performed an RNA-seq analysis of a D. simulans Lhr mutant strain, providing a rare opportunity to compare the function of a rapidly changing protein between two species.  Analysis of this data showed that Lhr in D. simulans, like in D. melanogaster represses repetitive elements. However, it also showed that the repetitive elements being regulated by Lhr in D. melanogaster and D. simulans are different. In summary, consistent with an ongoing arms race, ourdata strongly suggest that selfish elements directly drive the changes in the sequence of Lhr.