Predicting recombination suppression outside chromosomal inversions in Drosophila melanogaster using crossover interference theory.

Abstract

Recombination suppression in chromosomal inversion heterozygotes is a well-known but poorly understood phenomenon. Surprisingly, recombination suppression extends far outside of inverted regions where there are no intrinsic barriers to normal chromosome 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 these breakpoints in a process analogous to crossover interference. This hypothesis is qualitatively consistent with chromosome-wide patterns of recombination suppression extending to both inverted and uninverted regions of the chromosome. The present study generated quantitative predictions for this hypothesis using a probabilistic model of crossover interference with gamma-distributed inter-event distances. These predictions were then tested with experimental genetic data (>40,000 meioses) on crossing-over in intervals that are external and adjacent to four common inversions of Drosophila melanogaster. The crossover interference model accurately predicted the partially suppressed recombination rates in euchromatic intervals outside inverted regions. Furthermore, assuming interference does not extend across centromeres dramatically improved model fit and partially accounted for excess recombination observed in pericentromeric intervals. Finally, inversions with breakpoints closest to the centromere had the greatest excess of recombination in pericentromeric intervals, an observation that is consistent with negative crossover interference previously documented near Drosophila melanogaster centromeres. In conclusion, the experimental data support the interference hypothesis of recombination suppression, validate a mathematical framework for integrating distance-dependent effects of structural heterozygosity on crossover distribution, and highlight the need for improved modeling of crossover interference in pericentromeric regions.