Genomic signatures of extensive inbreeding in Isle Royale wolves, a population on the threshold of extinction

Abstract

The observation that small, isolated populations often suffer reduced fitness as a result of 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 sequenced complete genomes from an iconic inbred population, the gray wolves (Canis lupus) of Isle Royale. Through comparison with other wolf genomes from a variety of demographic histories, we found that Isle Royale wolf genomes contain extensive runs of homozygosity, but neither the overall level of heterozygosity nor the number of deleterious variants per genome were reliable predictors of inbreeding depression. These findings are consistent with the hypothesis that severe inbreeding depression results from increased homozygosity of strongly deleterious recessive mutations, which are more prevalent in historically large source populations. Our results have particular relevance in light of the recently proposed reintroduction of wolves to Isle Royale, as well as broader implications for management of genetic variation in the fragmented landscape of the modern world.