Using computational simulations to quantify genetic load and predict extinction risk

Small and isolated wildlife populations face numerous threats to extinction, among which is the deterioration of fitness due to an accumulation of deleterious genetic variation. Genomic tools are increasingly used to quantify the impacts of deleterious variation in small populations; however, these approaches remain limited by an inability to accurately predict the selective and dominance effects of individual mutations. Computational simulations of deleterious genetic variation offer an alternative and complementary tool that can help overcome these limitations, though such approaches have yet to be widely employed. In this Perspective, we aim to encourage conservation genomics researchers to adopt greater use of computational simulations to aid in quantifying and predicting the threat that deleterious genetic variation poses to extinction. We first provide an overview of the components of a simulation of deleterious genetic variation, describing the key parameters involved in such models. Next, we clarify several misconceptions about an essential simulation parameter, the distribution of fitness effects (DFE) of new mutations, and review recent debates over what the most appropriate DFE parameters are. We conclude by comparing modern simulation tools to those that have long been employed in population viability analysis, weighing the pros and cons of a genomics-informed simulation approach, and discussing key areas for future research. Our aim is that this Perspective will facilitate broader use of computational simulations in conservation genomics, enabling a deeper understanding of the threat that deleterious genetic variation poses to biodiversity.