An extension of the Cx(Co) m model of crossover patterning to account for experimental mortality in Drosophila melanogaster

Classic recombination experiments designed to test genetic and environmental treatments do not directly measure crossing-over, instead rates and distribution of meiotic events in F 1 meiocytes is inferred from genetic markers in F 2 adults. In Drosophila melanogaster females this procedure introduces a substantial “missing data problem” because 75% of meiotic chromatids segregate to polar body nuclei and another 11% are transmitted to inviable F 2 zygotes which cannot be scored for recombination. To address these sources of uncertainty and bias we extend the Cx(Co) m model of the data-generating process by assuming: 1) programmed double strand breaks occur as a Poisson point process, 2) crossover maturation is a stationary renewal process, 3) chromosome segregation is random one-half thinning of this process, 4) fertilization by X-versus Y-bearing sperm is mendelian, and 5) egg-to-adult survival is binomially distributed with a rate parameter determined by F 2 marker alleles. To quantify experimental mortality, we performed egg counts in a 6-point X chromosome testcross and marker-free controls on identical genetic backgrounds under standard laboratory conditions. The 19,927 fly dataset reveals 44% F 2 experimental mortality, and likelihood ratio tests support a model where 36 of the 44% is due to sex-specific, marker-associated viability defects. Variability in X chromosome genetic lengths with experimental mortality can be simulated and we provide case-control 80% power curves to guide experimental design. We propose that differential mortality should be the de facto null hypothesis when comparing F 2 recombinant fractions and provide probabilistic models of the data-generating process to improve characterization of patterns in F 1 meiotic events.