The Sherlock Lab - Experimental Evolution in Microbial Systems
The Sherlock lab uses experimental approaches to understand the
evolutionary process, specifically interested in i) what's the rate of
beneficial mutation, ii) what is the distribution of fitness effects of
beneficial mutations, iii) what are the identities of beneficial mutations
(and are they gain or loss of function, are they recessive, dominant or
overdominant, are the genic or regulatory?) and iv) how do each of these
change as a function of genotype, ploidy and environment. We are also
interested in how mutations that are beneficial in one environment fare in
others, to explore the trade-offs that inevitably occur when fitness
increases in a specific environment, and we are interested in exploring at
what level experimental evolution can be deterministic, and at what level
it is stochastic. We typically use short-term continuous (chemostat) and
serial batch culture experiments in conjunction with lineage tracking and
high throughput sequencing to understand the adaptive changes that occur
in yeast in response to selective pressures as they evolve in
vitro.
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Selected Recent Publications
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Kinsler, G., Li, Y., Sherlock, G.^, and Petrov, D.A.^ (2024). A shift from pleiotropic to modular adaptation revealed
by a high-resolution two-step adaptive walk. PLoS Biol 22(12):e3002848.
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Helsen, J.^, Reza, Md. H., Carvalho, R., Sherlock, G.^, and Dey, G.^ (2024). Spindle architecture constrains karyotype in budding yeast. Nature Cell Biology, 26(9):1496-1503.
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Chen, V.K.*, Johnson, M.*, Herissant, L.*, Humphrey, P.*, Yuan, D., Li, Y., Agarwala, A., Hoelscher, S.B. Petrov, D.A., Desai, M.M., Sherlock, G. Far From Home: Evolution of haploid and diploid populations reveals common, strong, and variable pleiotropic effects in non-home environments. Elife 12:e92899.
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Hays, M.*, Schwartz, K.*, Schmidtke, D.T., Aggeli, D., and Sherlock, G. (2023). Paths to adaptation under fluctuating nitrogen starvation: The spectrum of adaptive mutations in Saccharomyces cerevisiae is shaped by transposons and microhomology-mediated recombination. PLoS Genet. 19(5):e1010747.
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Aggeli, D.*, Li, Y.*, Sherlock, G. (2021). Changes in the distribution of fitness effects and adaptive mutational spectra following a single first step towards adaptation. Nat Commun. 12(1), 5193.
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