View Program - 63rd Annual Drosophila Research Conference

Homologous chromosome pairing is essential to all eukaryotes. Even so, our understanding of the molecular mechanisms underlying pairing is limited. We used changes in the pattern of pairing in Drosophila hybrids to find new mechanisms connected to pairing, and find that BLACK (intercalary) heterochromatin correlates with successful pairing. This discovery will help us understand pairing generally.
Although pairing is often associated with meiosis, it also occurs in somatic cells. Complete somatic pairing is the wild type state in Drosophila and other dipterans, but reproducible patterns of unpaired regions exist across the genome in interspecific Drosophila hybrids. Because chromosome pairing machinery exists in all eukaryotes, finding the genomic elements that drive this non-pairing will help us understand the drivers of pairing generally.
We crossed Drosophila melanogaster and Drosophila simulans, then used Hi-C to measure the rate of chromosome pairing with high resolution across the genome. Compared to within-species crosses, this hybrid Hi-C shows dramatic regions of high and low pairing. Repeating experiments in multiple tissues showed that hybrid pairing loss uniquely affects polytene tissues. In keeping with results from mosquitoes, an inversion between D. melanogaster and D. simulans showed reduced pairing around the inversion breakpoints, serving as a positive control.
While past microscopy experiments showed the existence of non-pairing regions, our high-resolution methods show a complex tapestry of high- and low- pairing regions of varying breadths and intensities. The clearly resolved peaks are consistent with the "button" model of pairing (multiple, discrete pairing sites) rather than the "zipper" model (continuous pairing along the chromosomes). We showed that local pairing maxima and minima are apparently uncorrelated with expected pairing drivers such as sequence similarity and insulator binding site density. High pairing is, however, highly correlated with BLACK chromatin. This chromatin is underreplicated in tissues with multiply replicated genomes such as the polytene tissue we measured. We hypothesize that replication machinery is slowed by BLACK chromatin, and helps maintain pairing when other pairing influencers are non-functional. Future work will test this underreplication hypothesis and show whether genes that influence reproductive incompatibility between these species also drive hybrid pairing loss.

Intercalary heterochromatin prevents local somatic pairing loss in interspecies Drosophila hybrids