# Predicting thresholds for population replacement gene drives

## TL;DR

This study explores how temperature affects the performance of gene drives designed to replace traits in populations, using fruit flies as a model.

## Contribution

The study introduces a single-generation fitness assay that can predict population replacement thresholds for gene drives more efficiently.

## Key findings

- EGI agents showed significant differences in behavior and performance not predicted by their genetic design.
- A temperature-dependent change in the predicted threshold for population replacement was observed in an EGI agent.
- The single-generation fitness assay can reduce time needed to estimate thresholds for TDGD strategies.

## Abstract

Threshold-dependent gene drives (TDGDs) could be used to spread desirable traits through a population, and are likely to be less invasive and easier to control than threshold-independent gene drives. Engineered Genetic Incompatibility (EGI) is an extreme underdominance system previously demonstrated in Drosophila melanogaster that can function as a TDGD when EGI agents of both sexes are released into a wild-type population.

Here we use a single generation fitness assay to compare the fecundity, mating preferences, and temperature-dependent relative fitness to wild-type of two distinct genotypes of EGI agents. We find significant differences in the behavior/performance of these EGI agents that would not be predicted a priori based on their genetic design. We report a surprising temperature-dependent change in the predicted threshold for population replacement in an EGI agent that drives ectopic expression of the developmental morphogen pyramus.

The single-generation fitness assay presented here could reduce the amount of time required to estimate the threshold for TDGD strategies for which hybrid genotypes are inviable. Additionally, this work underscores the importance of empirical characterization of multiple engineered lines, as behavioral differences can arise in unique genotypes for unknown reasons.

The online version contains supplementary material available at 10.1186/s12915-024-01823-2.