Suppression gene drive in continuous space can result in unstable persistence of both drive and wild-type alleles

Abstract

Rapid evolutionary processes can produce drastically different outcomes when studied in panmictic population models vs. spatial models. One such process is gene drive, which describes the spread of "selfish" genetic elements through a population. Engineered gene drives are being considered for the suppression of disease vectors or invasive species. While laboratory experiments and modelling in panmictic populations have shown that such drives can rapidly eliminate a population, it remains unclear if these results translate to natural environments where individuals inhabit a continuous landscape. Using spatially explicit simulations, we show that the release of a suppression drive can result in what we term "chasing" dynamics, in which wild-type individuals recolonize areas where the drive has locally eliminated the population. Despite the drive subsequently reconquering these areas, complete population suppression often fails to occur or is substantially delayed. This increases the likelihood that the drive is lost or that resistance evolves. We analyse how chasing dynamics are influenced by the type of drive, its efficiency, fitness costs, and ecological factors such as the maximal growth rate of the population and levels of dispersal and inbreeding. We find that chasing is more common for lower efficiency drives when dispersal is low and that some drive mechanisms are substantially more prone to chasing behaviour than others. Our results demonstrate that the population dynamics of suppression gene drives are determined by a complex interplay of genetic and ecological factors, highlighting the need for realistic spatial modelling to predict the outcome of drive releases in natural populations.

Keywords: biotechnology; ecological genetics; genetically modified organisms; population dynamics; population ecology; population genetics - theoretical.

Figure 1. Dynamics of suppression gene drives in our panmictic and spatial models.

(A) Drive heterozygotes (drive-carrying males for the Driving Y) were released at 1% frequency into a panmictic population of wild-type individuals, and the drive allele frequency and population size were tracked for each generation until the population size reached zero. The data displayed shows averages for 20 simulations. (B) Drive heterozygotes (drive-carrying males for the Driving Y) were released in a 0.01 radius circle into the middle of spatial population. Outcomes were tracked for 1000 generations for each simulation. The suppression rate specifies the proportion of simulations where the population was eliminated. Drive fitness and drive efficiency were varied on the left; low-density growth rate and migration value were varied on the right. Each point represents the average of at least 20 simulations.

Figure 2. The chasing phenomenon.

Snapshots of the population are shown in different generations (Gen) during a period of chasing of a female sterile homing drive. Red individuals have at least one drive allele and blue individuals have no drive alleles. Three scenarios with different parameters are shown where the chasing behavior is characterized by high (A), medium (B), and low (C) Green’s coefficient (GC), a measure of the degree of clustering. In (A), the drive cleared most of the area, but some wild-type individuals in a single patch persisted near the bottom of the area. These then spread into the large area of empty space, with the drive chasing them. In some cases, there can be multiple distinct chasing patches at the same time (B-C).

Figure 3. Effects of drive and ecological parameters on suppression outcomes in the spatial model.

Drive heterozygotes (drive-carrying males for the Driving Y) were released into the middle of a wild-type population. The proportion of different simulation outcomes is shown (“long-term chase” represents continued chasing behavior at generation 1000). Curves were obtained by averaging at least 100 simulation runs for each tested parameter value and then smoothed as described in the methods to reduce noise.

Figure 4. The effect of inbreeding on suppression outcomes in continuous space.

Drive heterozygotes (drive-carrying males for the Driving Y) were released into the middle of a wild-type population. The proportion of different simulation outcomes is shown. The relative inbreeding level specifies the preference a female gives to siblings when choosing a mate as compared to non-siblings (a value of 1 means that no preference is given, while a value of 2 means that siblings are twice as likely to be chosen), before adjustment by fitness. To show a greater dynamic range of outcomes, some default parameters were modified (female sterile homing drive: efficiency and fitness was reduced to 0.92, migration value was reduced to 0.035, and low-density growth rate was increased to 8; Driving Y: migration value was reduced to 0.0325; TADS suppression drive: efficiency and fitness was reduced to 0.8, migration value was reduced to 0.02, and low-density growth rate was increased to 12). Curves were obtained by averaging at least 100 simulation runs for each tested parameter value and then smoothed as described in the methods to reduce noise.

Figure 5. The effect of resistance allele formation on suppression outcomes.

Drive heterozygotes were released into a (A) spatial or (B) panmictic population. The proportion of different outcomes is shown for the female sterile homing drive and the both-sex sterile homing drive. Resistance outcomes refer to simulations where resistance alleles that preserve the function of the target gene reached at least 10% frequency with at least 500 individuals present. Each point represents the average of at least 100 simulations. The r1 rate is the fraction of resistance alleles that preserve the function of the target gene. To better show a range of outcomes, some default parameters were modified for the female sterile homing drive: efficiency and fitness was reduced to 0.92, migration value was reduced to 0.035, and low-density growth rate was increased to 8. Smoothing of curves was performed as described in the methods to reduce random noise.

Figure 6. The effect of drive release pattern on suppression outcomes in continuous space.

Drive heterozygotes (drive-carrying males for the Driving Y) were released randomly into a wild-type population at a level corresponding to 1% of the total population size. The proportion of different simulation outcomes is shown. The release interval specifies the full number of generations between releases in which no release occurs (a value of 0 corresponds to releases every generation). “S” represents a single random release (no continuous releases) and “C” represents a single central release. To show a greater dynamic range of outcomes, some default parameters were modified (female sterile homing drive: efficiency and fitness was reduced to 0.92, migration value was reduced to 0.035, and low-density growth rate was increased to 8; Driving Y: migration value was reduced to 0.0325; TADS suppression drive: efficiency and fitness was reduced to 0.8, migration value was reduced to 0.02, and low-density growth rate was increased to 12). Curves were obtained by averaging at least 100 simulation runs for each tested parameter value and then smoothed as described in the methods to reduce noise.