sherlock lab



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.


Selected Recent Publications

  1. Li, Y.*, Venkataram, S.*, Agarwala, A.*, Dunn, B., Petrov, D.A.^, Sherlock, G.^, Fisher, D.S.^ (2018). Hidden Complexity of Yeast Adaptation under Simple Evolutionary Conditions. Current Biology 28(4):515-525.e6.
    PubMed
  2. Aggeli, D., Karas, V.O., Sinnott-Armstrong, N.A., Varghese, V., Shafer, R.W., Greenleaf, W.J., Sherlock, G. (2018). Diff-seq: A high throughput sequencing-based mismatch detection assay for DNA variant enrichment and discovery. Nucleic Acids Research, in press.
    PubMed
  3. Venkataram, S., Dunn, B., Li, Y., Agarwala, A., Chang, J., Ebel, E.R., Geiler-Samerotte, K., Herissant, L., Blundell, J.R., Levy, S.F., Fisher, D.S., Sherlock, G and Petrov, D.A. (2016). Development of a Comprehensive Genotype-to-Fitness Map of Adaptation-Driving Mutations in Yeast. Cell 166(6):1585-1596.
    PubMed
  4. Levy, S.F., Blundell, J.R., Venkataram, S., Petrov, D.A., Fisher, D.S. and Sherlock, G. (2015). Quantitative evolutionary dynamics using high-resolution lineage tracking. Nature 519, 181-186.
    PubMed
  5. Kvitek, D.J., Sherlock, G. (2013). Whole Genome, Whole Population Sequencing Reveals That Loss of Signaling Networks Is the Major Adaptive Strategy in a Constant Environment. PLoS Genetics 9(11): e1003972.
    PubMed PLoS
Genetics
  6. Dunn, B., Paulish, T., Stanbery, A., Piotrowski, J., Koniges, G., Kroll, E., Louis, E.J., Liti, G., Sherlock, G., and Rosenzweig, F. (2013). Recurrent Rearrangement during Adaptive Evolution in an Interspecific Yeast Hybrid Suggests a Model for Rapid Introgression. PLoS Genetics 9(3): e1003366.
    PubMed PLoS
Genetics