Controlling the frequency dynamics of homing gene drives for intermediate outcomes

Abstract

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 frequency, a stochastic, individual allele-focused gene drive model accessible 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, presence and strength of a fitness cost for the gene drive, its dominance and the level of inbreeding. Four outcomes were consistently observed: Fixation, Loss, Temporary and Equilibrium. The latter two are defined by the frequency of the gene drive peaking then crashing or plateauing, respectively. No single variable determined the outcome of a drive, instead requiring a combination of variables. The difference between the conversion efficiency and resistance level differentiated the Temporary and Equilibrium outcomes. The frequency dynamics of the gene drive within outcomes varied extensively, with different variables driving this dynamics between outcomes. These simulation results highlight the possibility of fine-tuning gene drive outcomes and compensating through biotechnological design constraint imposed by population features. 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 outcome tailored to population management needs.