Biology subjects

Sharp, N.

Publications and source records attributed to Sharp, N..

3 recordsLinked to original sources

bioRxiv2026

Elevated mutation in haploid yeast driven by translesion synthesis

The impact of selection versus genetic drift on the evolution of mutation patterns is unclear. In Saccharomyces cerevisiae, which is predominantly diploid in nature, there is evidence that haploid cells have a higher mutation rate than diploids, suggesting that a haploid-specific mutator phenotype may have evolved due to the limited opportunity for selection to act on this rare cell type. Mutation in haploids was primarily elevated in late-replicating regions of the genome, implicating error-prone translesion synthesis (TLS) repair. Additional research has demonstrated that removing REV1, a gene responsible for initiating TLS, causes a reduction in haploid mutation rate. To assess whether the preferential use of this error-prone repair pathway by haploids explains the difference in genome-wide mutation patterns between cell types, we deleted REV1 in both diploid and haploid S. cerevisiae and estimated their mutation rates using a mutation accumulation experiment. Consistent with a previous study, we found a 50% higher single nucleotide mutation rate in REV1+ haploids than in REV1+ diploids. Deleting the REV1 gene caused this difference to vanish, with mutation rates in haploid and diploid rev1{Delta} lines converging on 2.4 x 10-10. Our results suggest that the mutagenic effect of translesion synthesis is much stronger in haploids, reflecting a limited opportunity for selection to act on mutation rates in rarer cells or smaller populations. We also find evidence that REV1 plays an important role in mitochondrial genome maintenance in both cell types.

evolutionary biology↗

bioRxiv2024

Mutations in yeast are deleterious on average regardless of the degree of adaptation to the testing environment

The role of spontaneous mutations in evolution depends on the distribution of their effects on fitness. Despite a general consensus that new mutations are deleterious on average, a handful of mutation accumulation experiments in diverse organisms instead suggest that of beneficial and deleterious mutations can have comparable fitness impacts, i.e., the product of their respective rates and effects can be roughly equal. We currently lack a general framework for predicting when such a pattern will occur. One idea is that beneficial mutations will be more evident in genotypes that are not well adapted to the testing environment. We tested this prediction experimentally in the laboratory yeast Saccharomyces cerevisiae by allowing nine replicate populations to adapt to novel environments with complex sets of stressors. After >1000 asexual generations interspersed with 41 rounds of sexual reproduction, we assessed the mean effect of induced mutations on yeast growth in both the environment to which they had been adapting and the alternative novel environment. The mutations were deleterious on average, with the severity depending on the testing environment. However, we find no evidence that the adaptive match between genotype and environment is predictive of mutational fitness effects.

evolutionary biology↗

bioRxiv2023

Domestic dogs maintain positive clinical, nutritional, and hematological health outcomes when fed a commercial plant-based diet for a year

ObjectiveDomestic dogs can maintain health on complete and well-balanced canine plant-based nutrition (K9PBN). Novel insight on health outcomes in dogs consuming K9PBN is of relevance to veterinary professionals and consumers given a growing interest in non-traditional dog foods with perceived health benefits, while considering potential safety concerns. We aimed to investigate nutritional equivalence by measuring clinical health outcomes in adult dogs fed K9PBN over twelve months compared to a meat-based diet at baseline. AnimalsFifteen clinically healthy adult dogs living in households in Los Angeles County, California. ProceduresProspective cohort study evaluating clinical, hematological, and nutritional parameters in dogs at 0, 6, and 12 months, including complete blood count (CBC), blood chemistry, cardiac biomarkers, plasma amino acids, and serum vitamin concentrations. ResultsClinically healthy, client-owned, adult dogs maintain health, based on physical exams, CBC, serum chemistry, plasma amino acids, serum vitamins, and cardiac biomarkers combined with client-reported observations, when fed commercial K9PBN over a twelve-month period. Clinical RelevanceThis study is the most comprehensive and longest known K9PBN investigation to date. It provides clinically important evidence-based nutrition data and new knowledge on outcomes in clinically healthy dogs who maintain health without consumption of animal-derived ingredients. Also, it is of major relevance to One Health paradigms since ingredients produced independent of industrial food animal production are both more sustainable and help to circumvent ethical dilemmas for maintenance of health in domestic dogs.

zoology↗