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Small populations with limited range are often threatened by inbreeding and reduced genetic diversity, which can reduce fitness and exacerbate population decline. One of the most extreme natural examples is the Devils Hole pupfish ( Cyprinodon diabolis ), an iconic and critically endangered species with the smallest known range of any vertebrate. This species has experienced severe declines in population size over the last 30 years and suffered major bottlenecks in 2007 and 2013, when the population shrunk to 38 and 35 individuals, respectively. Here, we analysed 30 resequenced genomes of desert pupfishes from Death Valley, Ash Meadows and surrounding areas to examine the genomic consequences of small population size. We found extremely high levels of inbreeding ( F ROH = 0.34–0.81) and an increased amount of potentially deleterious genetic variation in the Devils Hole pupfish as compared to other species, including unique, fixed loss-of-function alleles and deletions in genes associated with sperm motility and hypoxia. Additionally, we successfully resequenced a formalin-fixed museum specimen from 1980 and found that the population was already highly inbred prior to recent known bottlenecks. We thus document severe inbreeding and increased mutation load in the Devils Hole pupfish and identify candidate deleterious variants to inform management of this conservation icon.
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This content will become publicly available on January 12, 2027
Estimate of the mutation rate in the endangered Devils Hole pupfish provides support for the drift-barrier hypothesis at an outlying extreme
Abstract Mutation rates vary by three orders of magnitude across eukaryotes. The drift-barrier hypothesis proposes that drift overwhelms selection for lower mutation rates in small populations, leading to higher mutation rates over time due to gradual accumulation of mutator alleles. Here, we test this hypothesis in the smallest long-term isolated population in the world, the critically endangered Devils Hole pupfish (Cyprinodon diabolis). We estimated germline mutation rates in embryonic lethal and adult populations using autozygous segments caused by recent inbreeding events. Our estimate, 8.09 x 10-9per base pair per generation, is significantly higher than the average rate for actinopterygian fishes of 5.97 × 10−9(95% CI = 4.39 × 10−9- 7.55 × 10−9) and is lower than expected but still consistent with predictions from the drift-barrier hypothesis of 1.23 x 10-8(95% CI = 7.81 × 10−9– 1.93 × 10−8), based on a recent meta-analysis of vertebrate mutation rates by Bergeron et al. (2023). We find that embryonic lethal individuals have a higher mutation rate than mature adults, potentially reflecting a segregating lethal mutator allele or damage to the cellular environment during embryo death. We also analyzed the mutational spectra of germline mutations and find that spectra between embryonic lethal and mature adults were similar, as is the spectra in Devils Hole pupfish and other fishes, despite differences in environmental temperature and oxygen stresses. Mutation rates in this critically endangered species provide new insights at one extreme into the mechanisms driving mutation rate variation across vertebrates.
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- Award ID(s):
- 1938571
- PAR ID:
- 10668735
- Publisher / Repository:
- bioRxiv
- Date Published:
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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