Biology subjects

Camm, B. J.

Publications and source records attributed to Camm, B. J..

3 recordsLinked to original sources

bioRxiv2024

Controlling the frequency dynamics of homing gene drives for intermediate outcomes

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.

synthetic biology↗

bioRxiv2023

Acetylcholine esterase of Drosophila melanogaster: a laboratory model to explore applications of insecticide susceptibility gene drives

BACKGROUNDOne of the proposed applications of gene drives has been to revert pesticide resistant mutations back to the ancestral susceptible state. Insecticides that have become ineffective because of the rise of resistance could have reinvigorated utility and be used to suppress pest populations again, perhaps at lower application doses. RESULTSWe have created a laboratory model for susceptibility gene drives that replaces field-selected resistant variants of the acetylcholine esterase (Ace) locus of Drosophila melanogaster with ancestral susceptible variants. We constructed a CRISPR/Cas9 homing drive and found that homing occurred in many genetic backgrounds with varying efficiencies. While the drive itself could not be homozygosed, it converted resistant alleles into susceptible ones and produced recessive lethal alleles that could suppress populations. Our studies provided evidence for two distinct classes of Gene Drive Resistance (GDR): rather than being mediated by the conventional Non-Homologous End-joining (NHEJ) pathway, one seemed to involve short homologous repair and the other was defined by genetic background. Additionally, we used simulations to explore a distinct application of susceptibility drives; the use of chemicals to prevent the spread of synthetic gene drives into protected areas. CONCLUSIONSInsecticide susceptibility gene drives could be useful tools to control pest insects however problems associated with particularities of the target loci and GDR will need to be overcome for them to be effective. Furthermore, realistic patterns of pest dispersal and high insecticide exposure rates would be required if susceptibility were to be useful as a safety-switch to prevent the unwanted spread of gene drives.

genetics↗

bioRxiv2023

Modelling the effect of migration on the localisation and spread of a gene drive

Gene drives have the potential to address pressing ecological issues. Through the super-Mendelian inheritance of a gene drive, a trait can be spread through a population even in spite of a fitness cost. This ability to spread is both its greatest quality and detractor. We may not want a gene drive to spread universally. If a gene drive were designed to cause the collapse of a pest population, it may inadvertently cause the collapse of the entire species. Migration is the mechanism through which a gene drive can spread to distant populations. Understanding its effect on the progression of a gene drive is crucial to our ability to control a gene drive. While migration can spread the gene drive to other populations, equally it can bring in other alleles to the population that may disrupt the progression of the gene drive. Through our deterministic migration gene drive model we can assess the conditions in which a gene drive is likely to spread to unintended populations, and if a gene drive is likely to be displaced by incoming alleles.

genetics↗