Meiotic pairing through barcode-like satellite DNA repeats

During meiosis, chromosomes must find, pair and synapse with their homologous partner in the crowded milieu of the nucleus, without being entangled by non-homologous chromosomes1. Generally, homology detection is thought to rely on recombination between the homologous chromosomes. However, pairing and synapsis can occur in the absence of recombination2–9, suggesting alternate mechanisms which discriminate between homologous and non-homologous associations. In many eukaryotes, tandem repeats known as satellite DNA are known to facilitate inter-chromosomal associations10. Notably, their non-uniform distribution across chromosomes gives rise to homologue-specific satellite DNA ‘barcodes’11–13, which have been speculated to enable meiotic pairing14–17. However, the inability to manipulate these repeats in most model organisms means that satellite DNA function in meiotic pairing remains actively debated. Here, we use satellite DNA deletion, duplication, and translocation strains that are unique to Drosophila to demonstrate that repeat mismatches destabilize meiotic pairing, particularly at centromeres and pericentromeres. In the absence of satellite DNA, meiotic pairing is disrupted by the HORMAD protein, Mad2, and condensin II activity while a pachytene checkpoint 2 (pch2)-dependent meiotic delay can restore pairing. Furthermore, compromised homologue 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. Finally, we observe defective pairing and oocyte death in the progeny of D. melanogaster natural populations that have diverged in their satellite DNA content. Therefore, our findings resolve the debate on satellite DNA functionality by providing direct evidence for a role in meiotic pairing. We propose that this repeat-based pairing mechanism exerts an underappreciated selective pressure, constraining the divergence of these rapidly evolving tandem repeats within interbreeding natural populations.