Abstract

When faced with environmental changes, microbes enter a lag phase during which cell growth is arrested, allowing cells to adapt to the new situation. The discovery of the lag phase started the field of gene regulation and led to the unraveling of underlying mechanisms. However, the factors determining the exact duration and dynamics of the lag phase remain largely elusive. Naively, one would expect that cells adapt as quickly as possible, so they can resume growth and compete with other organisms. However, recent studies show that the lag phase can last from several hours up to several days. Moreover, some cells within the same population take much longer than others, despite being genetically identical. In addition, the lag phase duration is also influenced by the past, with recent exposure to a given environment leading to a quicker adaptation when that environment returns. Genome-wide screens in Saccharomyces cerevisiae on carbon source shifts now suggest that the length of the lag phase, the heterogeneity in lag times of individual cells, and the history-dependent behavior are not determined by the time it takes to induce a few specific genes related to uptake and metabolism of a new carbon source. Instead, a major shift in general metabolism, and in particular a switch between fermentation and respiration, is the major bottleneck that determines lag duration. This suggests that there may be a fitness trade-off between complete adaptation of a cell’s metabolism to a given environment, and a short lag phase when the environment changes.

Highlights

  • The seminal work of François Jacob and Jacques Monod revealed how microbes temporarily stop dividing when they encounter a shift in nutrients (Jacob and Monod 1961)

  • The majority of subsequent studies on the lag phase have focused on carbon source switches, and while the details of the mechanisms underlying gene regulation and adaptation have since been largely uncovered, little attention has gone to investigating the speed at which these processes take place

  • Respiration is induced to efficiently start growing on maltose. b Top: the natural variation in lag times between different S. cerevisiae strains correlates with the level of glucose repression of the respiratory metabolism

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Summary

Introduction

The seminal work of François Jacob and Jacques Monod revealed how microbes temporarily stop dividing when they encounter a shift in nutrients (Jacob and Monod 1961). Two recent studies measured the lag phase when yeast cells are transferred from glucose to a less-preferred carbon source such as maltose, galactose or ethanol (Fig. 1a) (Perez-Samper et al 2018; Cerulus et al 2018).

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