Estimate of the mutation rate in the endangered Devils Hole pupfish provides equivocal support for the drift-barrier hypothesis at an outlying extreme

Abstract

Mutation rates vary by 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 the gradual accumulation of mutator alleles. Here, we test this hypothesis in one of the smallest long-term isolated populations in the world, the endangered Devils Hole pupfish (Cyprinodon diabolis). We estimated germline mutation rates in adults and embryos that died prematurely using autozygous segments due to recent inbreeding events. Our estimate of 8.09 x 10-9 per base pair per generation was higher than the mean rate for actinopterygian fishes of 5.97 x 10-9 (95% CI: 4.39 x 10-9 - 7.55 x 10-9) but was lower than predicted for such a low effective population size based on a recent meta-analysis of vertebrate mutation rates and similar to species with much larger effective population sizes, contradicting the drift barrier hypothesis. We also found that embryos which died during development had a higher mutation rate than mature adults, potentially reflecting a segregating lethal mutator allele. We analyzed the mutational spectra of germline mutations and found that spectra between embryonic lethal and mature adults were similar and comparable to other fishes, despite environmental differences in temperature, oxygen saturation, and UV exposure. Mutation rates in this endangered species provide new insights into the mechanisms driving mutation rate variation across vertebrates at one extreme of low effective population size in nature.