Abstract
Gene drives are a promising genetic mechanism for managing invasive species and vector-borne diseases. Yet, their population dynamics have been predominantly studied through single-species models that fail to capture the complexity of real-world ecological systems. This thesis addresses critical knowledge gaps in understanding how ecological factors influence gene drive performance through three interconnected studies focused on invasive rodents. Rats and mice are selected as targets for gene drives since their high reproductive capacity and global pest status make them excellent candidates. These studies are also conducted in the ecologically diverse context of Aotearoa New Zealand, where use of such tools for managing rat populations is being considered.
Chapter 3 explores the impact of species interactions and fluctuating population size on gene drive dynamics using a four-species, stochastic, panmictic model with rats, mice, possums, and stoats. By implementing a homing gene drive targeting a haplosufficient female fertility gene in rats and mice, the results reveal that predation accelerates drive fixation. This is likely due to the suppressed population size and increased adult mortality, which promotes the higher recruitment of juvenile drive carriers. Population fluctuations emerge as an important influence in drive release strategies, since rapid population crashes can lead to major drive loss events.
Chapter 4 sought to improve our understanding of ship rat (Rattus rattus) population structure and dispersal. Traditional physical tracking methods are difficult for short-lived species and fail to capture effective dispersal. This work employs whole-genome sequencing and the disperseNN2 machine learning framework to estimate that ship rats have a mean dispersal distance of 498m per generation in a heterogeneous landscape in the South Island of New Zealand. Further, population structure analysis highlights gene flow corridors, and barriers across the landscape.
Chapter 5 synthesises the insights from Chapter 3 and 4, to explore gene drive dynamics in large-scale, multispecies models across heterogeneous landscapes. These models employ a new resource-based method for managing variable population density and spatial interactions, which dramatically reduces computational demands, enabling simulation of rodent populations across the entire South Island. Using published population densities, the model produces the first known estimate for rodent carrying capacity for the South Island: 36 million rats and 74 million mice. After adjusting for active pest control operations, the contemporary South Island population sizes are estimated at 31 million for rats and 60 million for mice. The model also suggests that elements of ecology are likely to prevent the gene drive chasing dynamics observed in previous models. Overall, the results demonstrate the utility of large-scale simulations for characterising population connectivity patterns, which will be critical for designing effective drive release strategies.
Collectively, this thesis advances our understanding of the interaction between ecological factors and gene drives, and demonstrates how species interactions, fluctuations in population size, and landscape-scale ecological complexity are fundamental considerations for predicting drive dynamics. The findings highlight that ecological factors operating across multiple scales can substantially influence drive outcomes, providing essential insights for the development of gene drives for pest management applications.