Understanding deleterious variation in wild populations

• Applicant: Professor Dr. Joseph Hoffman
• Subject Area: Evolution, Anthropology ; Ecology and Biodiversity of Animals and Ecosystems, Organismic Interactions
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 497640428

Inbreeding depression, the reduced fitness of offspring born to closely related parents, is a central topic in evolutionary and conservation biology. However, many aspects of inbreeding depression remain poorly understood, especially in the wild. In particular, despite decades of research, we still know little about the interplay between a species’ demographic history and the strength and genetic architecture of inbreeding depression.A substantial proportion of inbreeding depression is believed to result from recessive deleterious mutations that become homozygous in inbred offspring. Accordingly, population genetic theory predicts that the strength and genetic architecture of inbreeding depression will depend on the total burden of deleterious mutations (‘mutation load’) and on the frequencies of highly, moderately and weakly deleterious alleles. These should in turn be strongly influenced by historical population size changes such as bottlenecks, as small populations are expected to purge highly deleterious mutations more efficiently than large ones.To systematically evaluate the complex interplay between demography, detrimental mutations and inbreeding depression, we will take a novel, comparative genomic approach using pinnipeds. We will start by evaluating how long-term effective population sizes and recent bottlenecks have shaped genomic landscapes of deleterious variation. For this, we will apply innovative tools to whole genome resequencing data from 12 species spanning a demographic continuum from extreme anthropogenic bottlenecks to long-term stability. From there, we will elucidate the impact of recent bottlenecks on the strength and genetic architecture of inbreeding depression for a key fitness trait, survival to sexual maturity, across six species with contrasting histories.Finally, recent studies based on predicted mutation loads have ignited debate over the best genetic management strategies for small populations. Consequently, there is a pressing need to validate these predictions by linking them to the fitness of individuals in their natural environment. While it may seem reasonable to assume that predicted damaging mutations will explain a large proportion of the variation in fitness due to inbreeding, several factors may undermine their explanatory power, including the failure to account for beneficial alleles at loci under balancing selection. We will use a model pinniped system, the Antarctic fur seal, to quantify the explanatory power of predicted individual mutation loads in relation to other variance components including overdominance at the major histocompatibility complex, a cluster of immune genes that explains 20–70% of the variance in offspring survival in two related seal species.Overall, our project will deliver systematic insights into the interplay between demographic history, mutation loads and fitness variation in wild populations, with important implications for evolutionary and conservation biology.

• DFG Programme: Research Grants