Nathaniel Sharp
University of Wisconsin-Madison, WI·Ecology & Evolution
Every new genetic variant starts as a spontaneous mutation, yet the rate and type of mutations differ widely among organisms and cell types. It is still debated how natural selection and random chance (genetic drift) shape these mutation patterns.
- Fields
Ecology & Evolution
Genetics
Biology
- Topics
mutation rate
mutation spectrum
spontaneous mutation
- Grants
- 1 known grant, through Jul 2029
What they work on
- Test whether yeast cells of a species' rarer type, haploid or diploid, have higher mutation rates, by measuring ploidy-specific mutation patterns in haploid- and diploid-dominant yeast species.
- Identify candidate molecular mechanisms that could explain differences in mutation rate between haploid and diploid yeast cells.
- Separate the effects of parental sex and recombination on mutation, using fruit flies that lack meiotic DNA double-strand breaks, plus crosses that keep chromosomes in males or females only, followed by genome sequencing of accumulated mutations.
- Measure how aneuploidy, an abnormal chromosome number, affects male and female fruit flies, to explain the karyotype variation kept by the balance between new mutation and selection.
- Find gene variants that affect mating-type-specific reproduction in yeast, and switch mutants between mating types and ploidy states to detect trade-offs between sexual and asexual performance.
More about the research
This project connects the evolutionary causes of mutation patterns with the molecular processes that copy and repair DNA. It also examines how sex and recombination, the shuffling of chromosomes during the formation of eggs and sperm, interact with the mutation process.
Why it matters
Mutations produce the genetic variants behind inherited disorders and cancer. By testing how DNA replication and repair processes evolve and how they shape the genome, this work could improve scientists' ability to predict genetic change. It adds basic understanding of how evolutionary forces influence genome maintenance.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Caitlin Smukowski Heil
North Carolina State University, NC·Genetics
Build genome-wide recombination maps for multiple Saccharomyces uvarum populations using whole genome sequencing, and compare how double-strand breaks are repaired as crossovers versus non-crossover gene conversions.
Patricia Wittkopp
University of Michigan, MI·Genetics
Identify the genes and specific DNA changes behind trait differences within and between fruit fly (Drosophila) species, and determine how they alter molecular, cellular and developmental processes.
Juan Lucas Argueso
Colorado State University-Fort Collins, CO·Genetics
Measure rates of copy number variation (CNV), loss of heterozygosity (LOH), and whole-chromosome gain or loss in dividing and meiotic budding yeast cells, using custom, highly sensitive cell-based assays.
The school
University of Wisconsin-Madison: 91 labs on PI Pages, $1.9B a year on research, 854 research doctorates a year.
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