Fig. 1: Improved fitness and consistent blocking of gene drive homing in the updated anti-drive strain.
A Heterozygous Ag(QFS)1 gene drive (in red) crossed to WT individuals (in grey) produce progeny most of which inherits the drive allele through homing (indicated with the black arrow) in the germline (left-hand panel). Trans-heterozygous individuals carrying one allele of the Ag(QFS)1 drive and one of the Ag(Vasa:A4)2 anti-drive (in red and blue, respectively) crossed to WT result in Mendelian inheritance of both the gene drive and anti-drive alleles (right-hand panel) due to blocking of Cas9 in the germline. B Dot plots overlapping bar plots of the number of eggs and the relative hatching rate calculated from bulk oviposition of homozygous males and females Ag(Vasa:A4)+/+ (light grey bar) and Ag(Vasa:A4)2+/+ (dark grey) compared to wild-type control (white). There were no statistically significant differences between hatching rates, while there was for the egg number between the Ag(Vasa:A4)+/+ and the wild type (p = 0.458, Kruskal–Wallis test). Bar charts indicate mean percentage values and error bars indicate standard error of the mean from all biological samples assessed for each cross. Three biologically independent experiments were examined for each cross, consisting of 100 ovipositing females in each cross. The respective raw data are provided in the Source Data file. C Scatter plot showing the transgenic rate from individual deposition of Ag(QFS)1 (red dots) and the Ag(Vasa:A4)2 (blue dots) alleles in the progeny from the crosses of male and female anti-drive heterozygotes, gene drive heterozygotes, and drive/anti-drive trans-heterozygous for the two alleles, with the corresponding wild-type. Both male and female trans-heterozygotes showed complete inhibition of homing and Mendelian rates of the drive allele inheritance (p < 0.0001, Kruskal–Wallis test). Bar charts (light grey for males and white for females transgenics) indicate mean percentage values and error bars indicate standard error of the mean of transmission rates from all biological samples assessed for each cross. A minimum of 11 biologically independent samples (ovipositing females) were examined per independent experiment. Two independent experiments were performed for drive/anti-drive trans-heterozygotes, one experiment was performed for the anti-drive heterozygotes, and the data for gene drive heterozygotes were sourced from7. The respective raw data are provided in the Source Data file.
