Recombination experiments with inversion heterozygotes

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.