Lucas Carey

Evolutionary Biology and Complex Systems ; Department of Experimental and Health Sciences ; Universitat Pompeu Fabra ; Barcelona

Exploration of genetic and phenotypic space through stochastic variation in fitness (Monday April 27th, 9h-10h)

The fitness of single cells in an isogenic population growing in the same environment shows a large degree of variability. In order to characterize the intracellular state of cells that differ only by stochastic differences in growth rate, we developed a method – FitFlow – that physically sorts cells by stochastic differences in their fitness. We find that stochastically slow growing yeast have a substantially altered transcriptome that, to a limited extent, resembles that of cells growing slowly in a nutrient-limited chemostat. Stochastically slow growing cells have a high level of transcriptional diversity: more genes, novel transcripts and antisense transcripts, as well as activation of genes on the 2-micron plasmid and two endogenous viruses. Moreover, slow cells up-regulate transposons, show a DNA damage response, and have reduced RNA polymerase fidelity. Our results therefore suggest that slow cells explore a larger genotypic - and so phenotypic - space.