Experimental evolution of bet hedging

Hubertus J. E. Beaumont, Jenna Gallie, Christian Kost, Gayle C. Ferguson & Paul B. Rainey

Abstract | Bet hedging -stochastic switching between phenotypic states— is a canonical example of an evolutionary adaptation that facilitates persistence in the face of fluctuating environmental conditions. Although bet hedging is found in organisms ranging frombacteria to humans, direct evidence for an adaptive origin of this behaviour is lacking. Here we report the de novo evolution of bet hedging in experimental bacterial populations. Bacteria were subjected to an environment that continually favoured new phenotypic states. Initially, our regime drove the successive evolution of novel phenotypes by mutation and selection; however, in two (of 12) replicates this trend was broken by the evolution of bet-hedging genotypes that persisted because of rapid stochastic phenotype switching. Genome re-sequencing of one of these switching types revealed ninemutations that distinguished it fromthe ancestor. The final mutation was both necessary and sufficient for rapid phenotype switching; nonetheless, the evolution of bet hedging was contingent upon earliermutations that altered the relative fitness effect of the finalmutation. These findings capture the adaptive evolution of bet hedging in the simplest of organisms, and suggest that riskspreading strategies may have been among the earliest evolutionary solutions to life in fluctuating environments.

http://www.nature.com/nature/journal/v462/n7269/pdf/nature08504.pdf

Direct cell reprogramming is a stochastic process amenable to acceleration

Jacob Hanna*, Krishanu Saha*, Bernardo Pando, Jeroen van Zon, Christopher J. Lengner, Menno P. Creyghton, Alexander van Oudenaarden & Rudolf Jaenisch

Abstract | Direct reprogramming of somatic cells into induced pluripotent stem (iPS) cells can be achieved by overexpression of Oct4, Sox2, Klf4 and c-Myc transcription factors, but only a minority of donor somatic cells can be reprogrammed to pluripotency. Here we demonstrate that reprogramming by these transcription factors is a continuous stochastic process where almost all mouse donor cells eventually give rise to iPS cells on continued growth and transcription factor expression. Additional inhibition of the p53/p21 pathway or overexpression of Lin28 increased the cell division rate and resulted in an accelerated kinetics of iPS cell formation that was directly proportional to the increase in cell proliferation. In contrast, Nanog overexpression accelerated reprogramming in a predominantly cell-division-rate-independent manner. Quantitative analyses define distinct cell-division-rate-dependent and -independent modes for accelerating the stochastic course of reprogramming, and suggest that the number of cell divisions is a key parameter driving epigenetic reprogramming to pluripotency.

http://www.nature.com/nature/journal/vaop/ncurrent/pdf/nature08592.pdf