TY - JOUR T1 - Genetic architecture and lifetime dynamics of inbreeding depression in a wild mammal JF - bioRxiv DO - 10.1101/2020.05.27.118877 SP - 2020.05.27.118877 AU - M.A. Stoffel AU - S.E. Johnston AU - J.G. Pilkington AU - J.M Pemberton Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/05/30/2020.05.27.118877.abstract N2 - Inbreeding depression is a phenomenon of long-standing importance, but we know surprisingly little about its genetic architecture, precise effects and life-history dynamics in wild populations. Here, we combined 417K imputed SNP genotypes for 5952 wild Soay sheep with detailed long-term life-history data to explore inbreeding depression on a key fitness component, annual survival. Inbreeding manifests in long runs of homozygosity (ROH) and these are abundant in Soay sheep, covering on average 24% of the autosomal genome and up to 50% in the most inbred individuals. The ROH landscape is shaped by recombination rate variation and differs widely across the genome, including islands where up to 87% of the population have an ROH and deserts where the ROH prevalence is as low as 4%. We next quantified individual inbreeding as the proportion of the autosomal genome in ROH (FROH) and estimated its effect on annual survival. The consequences of inbreeding are severe; a 10% increase in FROH was associated with a 68% [95% CI 55-78%] decrease in the odds of survival. However, the strength of inbreeding depression is dynamic across the lifespan. We estimate depression to peak in young adults, to decrease into older ages and to be weaker in lambs, where inbreeding effects are possibly buffered by maternal care. Finally, using a genome-wide association scan on ROH, we show that inbreeding causes depression predominantly through many loci with small effects, but we also find three regions in the genome with putatively strongly deleterious mutations. Our study reveals population and genome-wide patterns of homozygosity caused by inbreeding and sheds light on the strength, dynamics and genetic architecture of inbreeding depression in a wild mammal population.Competing Interest StatementThe authors have declared no competing interest. ER -