Abstract
Author SummaryWhen microbes grow in a mixture of different nutrients, they repress the metabolism of nonpreferred nutrients such as complex carbohydrates until preferred nutrients, like glucose, are depleted. While this “catabolite repression” allows cells to use the most efficient nutrients first, it also comes at a cost because the switch to nonpreferred nutrients requires the de-repression of specific genes, and during this transition cells must temporarily stop dividing. Naively, one might expect that cells would activate the genes needed to resume growth in the new environment as quickly as possible. However, we find that the length of the growth lag that occurs when yeast cells are switched from the preferred carbon source glucose to alternative nutrients like maltose, galactose, or ethanol differs between wild yeast strains. By repeatedly alternating a slow-switching strain between glucose and maltose, we obtained mutants that show shortened lag phases. Although these variants can switch rapidly between carbon sources, they show reduced growth rates in environments where glucose is available continuously. Further analysis revealed that mutations in genes like HXK2 cause variations in the degree of catabolite repression, with some mutants showing leaky or stochastic maltose gene expression. Together, these results reveal how different gene regulation strategies can affect fitness in variable or stable environments.
Highlights
A stable environment generally favors organisms that are welladapted to that specific niche [1,2,3]
Glucose acts as a primary signal, triggering a regulatory cascade that results in repression of the consumption of alternative carbon sources, such as maltose, galactose, or ethanol
At the other extreme we supplemented growth media with only 0.5% glucose, a condition that allows cells to first grow quickly by fermenting glucose, and reprogram their metabolic genes to switch to respiratory growth on the ethanol accumulated during the fermentation phase (Figure 1 and Figure S1)
Summary
A stable environment generally favors organisms that are welladapted to that specific niche [1,2,3]. Because the expression of nonnecessary metabolic routes and genes is costly [3,10,11], microbes often use catabolite repression mechanisms to preferentially consume nutrients that afford high growth rates. This way, nonpreferred nutrient genes are only expressed when other, more preferred nutrients have been depleted. Other effectors include Snf, the yeast homologue of mammalian AMP-activated PK, and Rgt1 Both of these proteins effect catabolite repression by triggering the transcriptional rewiring of a small subset of genes, many of which are directly involved in the uptake and metabolism of alternative carbon sources [12,13,14,16]
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