Controlling the frequency dynamics of homing gene drives for intermediate outcomes
Controlling the frequency dynamics of homing gene drives for intermediate outcomes
Tags: CRISPR, Modeling, ResistanceCamm B., Fournier-Level A., G3: Genes|Genomes|Genetics, 2025.
Gene drives have enormous potential for solving biological issues by forcing the spread of desired alleles through populations. However, to safeguard from the potentially irreversible consequences on natural populations, gene drives with intermediate outcomes that neither fixate nor get removed from the population are of outstanding interest. To elucidate the conditions leading to intermediate gene drive outcomes, a stochastic, individual allele-focused gene drive model was developed to simulate the diffusion of a homing gene drive in a population. The frequencies of multiple alleles at a locus targeted by a gene drive were tracked under various scenarios. These explored the effect of gene drive conversion efficiency, strength and frequency of resistance alleles, dominance and strength of a fitness cost for the gene drive, and the level of inbreeding. Four outcomes were consistently observed: fixation, loss, temporary, and equilibrium. The latter 2 are defined by the frequency of the gene drive peaking then crashing or plateauing, respectively. No single variable determined the outcome of a drive. The difference between the conversion efficiency and resistance level, modeled quantitatively, differentiated the temporary and equilibrium outcomes. The frequency dynamics of the gene drive within outcomes varied extensively, with different variables driving these dynamics between outcomes. These simulation results highlight the possibility of fine-tuning gene drive outcomes and frequency dynamics. To that end, we provide a web application implementing our model, which will guide the safer design of gene drives able to achieve a range of controllable outcomes tailored to population management needs.
