Genomic Flatlining in the Endangered Island Fox

Genetic studies of rare and endangered species often focus on defining and preserving genetically distinct populations, especially those having unique adaptations [1, 2]. Much less attention is directed at understanding the landscape of deleterious variation, an insidious consequence of geographic isolation and the inefficiency of natural selection to eliminate harmful variants in small populations [3–5]. With population sizes of many vertebrates decreasing and isolation increasing through habitat fragmentation and loss, understanding the extent and nature of deleterious variation in small populations is essential for predicting and enhancing population persistence. The Channel Island fox (Urocyon littoralis) is a dwarfed species that inhabits six of California’s Channel Islands and is derived from the mainland gray fox (U. cinereoargenteus). These isolated island populations have persisted for thousands of years at extremely small population sizes [6, 7] and, consequently, are a model for testing ideas about the accumulation of deleterious variation in small populations under natural conditions. Analysis of complete genome sequence data from island foxes shows a dramatic decrease in genome-wide variation and a sharp increase in the homozygosity of deleterious variants. The San Nicolas Island population has a near absence of variation, demonstrating a unique genetic flatlining that is punctuated by heterozygosity hotspots, enriched for olfactory receptor genes and other genes with high levels of ancestral variation. These findings question the generality of the small-population paradigm that maintains substantial genetic variation is necessary for short- and long-term persistence. •Genomic monomorphism on a scale not seen previously in eukaryotes is shown•Deleterious variation and loss-of-function mutations are not purged•Drift, without balancing selection, accounts for peaks of heterozygosity•Persistence despite the absence of variation questions its role in small populations Robinson et al. show that the island fox has drastically reduced genetic variation and high levels of deleterious mutations, suggesting that selection has not purged harmful variants. Remarkably, the San Nicolas Island fox has a near absence of variation, questioning the importance of genetic variation in the long-term persistence of small populations.