Purging of Strongly Deleterious Mutations Explains Long-Term Persistence and Absence of Inbreeding Depression in Island Foxes

Abstract

Summary The recovery and persistence of rare and endangered species are often threatened by genetic factors, such as the accumulation of deleterious mutations, loss of adaptive potential, and inbreeding depression [1]. Island foxes (Urocyon littoralis), the dwarfed descendants of mainland gray foxes (U. cinereoargenteus), have inhabited California’s Channel Islands for >9,000 years [2-4]. Previous genomic analyses revealed island foxes have exceptionally low levels of diversity and elevated levels of putatively deleterious variation [5]. Nonetheless, all six populations have persisted for thousands of generations, and several populations rebounded rapidly following recent severe bottlenecks [6, 7]. Here, we combine morphological and genomic data with population genetic simulations to determine the mechanism underlying the enigmatic persistence of these foxes. First, through analysis of genomes from 1929-2009, we show that island foxes have remained at small population sizes with low diversity for many generations. Second, we present morphological data indicating an absence of inbreeding depression in island foxes, confirming that they are not afflicted with congenital defects common to other small and inbred populations. Lastly, our population genetic simulations suggest long-term small population size results in a reduced burden of strongly deleterious recessive alleles, providing a mechanism for the absence of inbreeding depression in island foxes. Importantly, the island fox illustrates a scenario in which genetic restoration through human-assisted gene flow could be a counterproductive or even harmful conservation strategy. Our study sheds light on the puzzle of island fox persistence, a unique success story that provides a model for the preservation of small populations.

Demographic history shaped geographical patterns of deleterious mutation load in a broadly distributed Pacific Salmon

“…Overall, these results are consistent with recent empirical findings in which small populations or populations at the expansion front carry more homozygous derived deleterious mutations [26,27,86]. These deleterious mutations in homozygous state are expected to be purged by purifying selection [23,92]. Populations from Cascadia, with higher effective population sizes, contain a higher number of putatively deleterious variants in heterozygous state, as expected from population genetics theory.…”

Evolutionary genomics of structural variation in Asian rice (Oryza sativa) and its wild progenitor (O. rufipogon)

“…For example, clonal variants tend to accrue recessive deleterious variants over time, because these variants are under recessive selection and permanently held in a heterozygous state (37). Similarly, forward simulations have shown that moderately and weakly deleterious variants accumulate under various demographic regimes (84). Here we have shown that the SV burden is elevated by 25% to 35% in our japonica and indica samples relative to rufipogon (Fig.…”

Purging of highly deleterious mutations through severe bottlenecks in Alpine ibex

“…A major gap in our understanding is how reduced selection efficacy and purging jointly determine the mutation load in wild populations. Theoretical predictions are well established 13,15,18,20 but empirical evidence is conflicting 9,21,22 including for humans (see e.g. 23–31 .…”

“…23–31 . Previous research used changes in fitness to infer possible purging events, 7,20,32–34 , but changes in fitness can result from causes unrelated to purging 12,35 . Direct evidence for purging exists only for isolated mountain gorilla populations that split off larger lowland populations ~20’000 years ago 36 .…”

“…Empirical evidence for purging in the wild is scarce 7,20,36 . Here, we show that a few dozen generations were sufficient to reduce the burden of highly deleterious mutations.…”