The observation that small isolated populations often suffer reduced fitness from inbreeding depression has guided conservation theory and practice for decades. However, investigating the genome-wide dynamics associated with inbreeding depression in natural populations is only now feasible with relatively inexpensive sequencing technology and annotated reference genomes. To characterize the genome-wide effects of intense inbreeding and isolation, we performed whole-genome sequencing and morphological analysis of an iconic inbred population, the gray wolves (Canis lupus) of Isle Royale. Through population genetic simulations and comparison with wolf genomes from a variety of demographic histories, we find evidence that severe inbreeding depression in this population is due to increased homozygosity of strongly deleterious recessive mutations. Our results have particular relevance in light of the recent translocation of wolves from the mainland to Isle Royale, as well as broader implications for management of genetic variation in the fragmented landscape of the modern world.

Deleterious mutations decrease reproductive fitness and are ubiquitous in genomes. Given that many organisms face ongoing threats of extinction, there is interest in elucidating the impact of deleterious variation on extinction risk and optimizing management strategies accounting for such mutations. Quantifying deleterious variation and understanding the effects of population history on deleterious variation are complex endeavors because we do not know the strength of selection acting on each mutation. Further, the effect of demographic history on deleterious mutations depends on the strength of selection against the mutation and the degree of dominance. Here we clarify how deleterious variation can be quantified and studied in natural populations. We then discuss how different demographic factors, such as small population size, nonequilibrium population size changes, inbreeding, and gene flow, affect deleterious variation. Lastly, we provide guidance on studying deleterious variation in nonmodel populations of conservation concern.

Genome admixture in two endemic North American wolf species.