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Predicting thresholds for population replacement gene drives.

Anna Janzen1,2, Ratnasri Pothula1,2, Adam Sychla1,2

  • 1Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, 55455, MN, USA.

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Engineered Genetic Incompatibility (EGI) can act as a threshold-dependent gene drive (TDGD). This study reveals unexpected performance differences between EGI agent genotypes and a surprising temperature effect on population replacement thresholds.

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Area of Science:

  • Population genetics
  • Genetic engineering
  • Synthetic biology

Background:

  • Threshold-dependent gene drives (TDGDs) offer controllable trait propagation.
  • Engineered Genetic Incompatibility (EGI) is an extreme underdominance system functioning as a TDGD in Drosophila melanogaster.

Purpose of the Study:

  • Compare fecundity, mating preferences, and relative fitness of two EGI agent genotypes.
  • Investigate temperature-dependent performance and population replacement thresholds for EGI systems.

Main Methods:

  • Single generation fitness assay in Drosophila melanogaster.
  • Comparison of EGI agent genotypes against wild-type populations.
  • Analysis of mating behavior and temperature-dependent fitness.

Main Results:

  • Significant, unpredictable differences in EGI agent behavior and performance were observed.
  • A temperature-dependent shift in the population replacement threshold was identified for a pyramus-expressing EGI agent.
  • Empirical data revealed genotype-specific variations not predicted by genetic design.

Conclusions:

  • A single-generation fitness assay can accelerate threshold estimation for TDGD strategies with inviable hybrids.
  • Empirical characterization of multiple engineered lines is crucial due to unpredictable genotypic variations.
  • Understanding genotype-environment interactions is key for EGI system development and control.