Using genomic predictions of deleterious mutations to characterise the genetic architecture of inbreeding depression in a wild vertebrate, the banded mongoose

• Applicant: Professor Dr. Joseph Hoffman
• Subject Area: Sensory and Behavioural Biology ; General Genetics and Functional Genome Biology ; Evolution, Anthropology ; Ecology and Biodiversity of Animals and Ecosystems, Organismic Interactions
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 568169799

Inbreeding depression, the reduced fitness of offspring born to closely related parents, is a central topic in evolutionary and conservation biology. However, despite decades of research, many aspects of inbreeding depression remain poorly understood, especially in wild populations. In particular, the genetic architecture of inbreeding depression remains unclear, including how different regions of the genome contribute, which genes are involved, whether coding or regulatory mutations are more important, and whether large numbers of weakly deleterious mutations or smaller numbers of moderately to highly deleterious mutations are responsible.To address this issue, we propose a comprehensive investigation of the genetic basis of inbreeding depression in the banded mongoose (Mungos mungo) using a novel approach based on predicted deleterious mutations. Specifically, we will apply evolutionary conservation and functional prediction methods to identify and characterize deleterious mutations from whole genome resequencing data. We will then assess their contributions to inbreeding depression using a large molecular pedigree and three decades of individual-based life-history and behavioural data.Building upon our previous DFG project demonstrating strong inbreeding depression for male reproductive success in the banded mongoose, we will sequence the whole genomes of all 250 adult males present in the study population since 1995. To explore the genetic architecture of inbreeding depression, we will use several complementary approaches. First, we will map the fitness effects of deleterious mutations across the genome to pinpoint genomic hotspots of inbreeding depression. Second, we will categorize deleterious mutations by gene ontology to determine which molecular functions and biological processes are most affected by inbreeding. Third, we will compare the fitness effects of deleterious mutations in coding versus non-coding regions of the genome to evaluate the relative importance of mutations that alter protein structure and function versus those in regulatory elements, such as promotors, that influence gene expression. Additionally, we will analyse repeated measures of life-history and behavioural traits to investigate how deleterious mutations affect reproductive success via the expression of phenotypic traits such as body mass, parasite loads and mate-guarding behaviour.Overall, this project will provide unprecedentedly detailed insights into the genetic basis of inbreeding depression in a wild population, improving our understanding of its evolutionary and conservation implications.

• DFG Programme: Research Grants