Interference hypothesis for recombination suppression in chromosomal inversion heterozygotes: A formal genetics analysis in Drosophila melanogaster

Abstract

ABSTRACTSuppressed recombination in chromosomal inversion heterozygotes is a well-known but poorly understood phenomenon. Recombination suppression is the result of at least four different regional effects of inversion heterozygosity; surprisingly, this includes areas outside inversions where there are no barriers to normal pairing, synapsis, double strand break formation, or recovery of crossover products. The interference hypothesis of recombination suppression proposes heterozygous inversion breakpoints possess chiasma-like properties such that recombination suppression extends from breakpoints in a process analogous to crossover interference. This hypothesis is qualitatively consistent with chromosome-wide patterns of recombination suppression, unifying the various regional effects under a single mechanism. The present study generates quantitative predictions for this hypothesis using a probabilistic model of crossover interference as a stationary renewal point process with gamma-distributed interarrival distances. These predictions were tested with formal genetic data (>40,000 meioses) on crossing-over in intervals external and adjacent to four cosmopolitan inversions of Drosophila melanogaster. The decay of recombination suppression differs for each of the four cosmopolitan inversions, with a strong dependence on proximity to the centromere. Counterintuitively, greater than expected recombination was observed in centromeric regions for the most proximally placed inversions. Structural features of chromosomes are discussed as potentially confounding variables in modelling recombination suppression. The true form of the decay function is not currently known and will require high-resolution mapping of rare crossover events in regions immediately adjacent to inversion breakpoints. A simple extension of the present experimental system can be conducted as a genetic screen for those rare crossover events.