Meiotic pairing through barcode-like satellite DNA repeats

During meiosis, chromosomes must find, pair, and synapse with their homologous partners in the crowded milieu of the nucleus. Although homology detection generally relies on recombination, pairing can occur in its absence, suggesting alternative mechanisms. Here, we show that the barcode-like arrangement of non-coding satellite DNA repeats facilitates homologue pairing during meiosis. Using satellite DNA deletion, duplication, and translocation strains, we demonstrate that repeat mismatches perturb meiotic pairing, particularly at centromeres and pericentromeres. Notably, pairing defects are also observed in the progeny of D. melanogaster natural populations that have diverged in their satellite DNA content. In the absence of satellite DNA homology, pairing is antagonised by the HORMAD protein, Mad2, while a Pachytene checkpoint 2 (Pch2)-dependent meiotic delay restores pairing. In addition, compromised meiotic pairing is strongly correlated with mid-oogenesis cell death, a quality control mechanism that likely culls defective oocytes to prevent chromosome mis-segregation and aneuploidy. Taken together, our findings reveal an important role for satellite DNA repeats during meiotic homology detection. We propose that this repeat-based pairing mechanism exerts an underappreciated selective pressure, constraining the divergence of rapidly evolving satellite DNA within interbreeding natural populations.