Genetic determinants of the Saccharomyces cerevisiae lag phase

Micro-organisms commonly live in an environment with dynamic nutrient availability. This makes it crucial for an organism's fitness to appropriately respond to environmental changes, since each metabolic response requires an investment of energy, time and precious building blocks. In many cases, such metabolic rewiring is accompanied by a period of delayed growth, often referred to as a lag phase. The length of this lag phase can vary significantly between organisms, environments and phenotypes, but also shows large natural variation between member of the same species, raising a number of questions: Why would an organism have a long lag phase? Are there any benefits to having a longer lag phase? Which factors determine lag phase length? How is the lag phase tuned, and which genetic factors underlie its natural variation? In this project, we aim to answer these questions using the yeast Saccharomyces cerevisiae as a model system, specifically focusing on its response to an environmental switch from glucose to a secondary carbon source. First, we examined the extent of natural variation in lag phase length between genetically diverse yeast strains for different types of carbon source shifts. We show that there is indeed significant natural variation in lag phase length between different genotypes, and find that a strain's respiratory capacity can be pinpointed as a major factor influencing its lag phase. We then harnessed this natural variation in lag phase length in a Quantitative Trait Loci analysis to identify genetic factors underlying the lag phase phenotype. Here, we find that allelic variation in a so-far uncharacterized gene explains a large part of the observed natural variation in lag phase length. Using a combination of complementary experimental techniques, we show that this gene encodes a key fine-tuner of lag phase, most likely through regulation of respiration. Lastly, we explored potential benefits and disadvantages associated with the lag phase phenotype. Using competition assays, we find strong indications for a link between the strength of catabolite repression of respiration and the lag phase. Together, our results suggest that the observed natural variation in lag phase length can be attributed to the tuning of glucose repression of respiration.

Jaar van publicatie:2022

Toegankelijkheid:Open