Abstract
BackgroundControl of growth rate is mediated by tight regulation mechanisms in all free-living organisms since long-term survival depends on adaptation to diverse environmental conditions. The yeast, Saccharomyces cerevisiae, when growing under nutrient-limited conditions, controls its growth rate via both nutrient-specific and nutrient-independent gene sets. At slow growth rates, at least, it has been found that the expression of the genes that exert significant control over growth rate (high flux control or HFC genes) is not necessarily regulated by growth rate itself. It has not been determined whether the set of HFC genes is the same at all growth rates or whether it is the same in conditions of nutrient limitation or excess.ResultsHFC genes were identified in competition experiments in which a population of hemizygous diploid yeast deletants were grown at, or close to, the maximum specific growth rate in either nutrient-limiting or nutrient-sufficient conditions. A hemizygous mutant is one in which one of any pair of homologous genes is deleted in a diploid, These HFC genes divided into two classes: a haploinsufficient (HI) set, where the hemizygous mutants grow slower than the wild type, and a haploproficient (HP) set, which comprises hemizygotes that grow faster than the wild type. The HI set was found to be enriched for genes involved in the processes of gene expression, while the HP set was enriched for genes concerned with the cell cycle and genome integrity.ConclusionA subset of growth-regulated genes have HFC characteristics when grown in conditions where there are few, or no, external constraints on the rate of growth that cells may attain. This subset is enriched for genes that participate in the processes of gene expression, itself (i.e. transcription and translation). The fact that haploproficiency is exhibited by mutants grown at the previously determined maximum rate implies that the control of growth rate in this simple eukaryote represents a trade-off between the selective advantages of rapid growth and the need to maintain the integrity of the genome.
Highlights
Control of growth rate is mediated by tight regulation mechanisms in all free-living organisms since long-term survival depends on adaptation to diverse environmental conditions
high flux control (HFC) at rapid growth in comparison to nutrient-limited chemostats at low growth rates Results from the present study demonstrate that the functional distribution of HFC genes detected by competitions in turbidostats is very different from the HFC genes detected by our earlier Category 2 experiments [4] that involved competitions in nutrient-limited chemostats
Genetic control of growth rate is qualitatively, but not quantitatively, correlated with, growth rate regulation of gene expression Previously, we have shown that genes involved in the processes of gene expression are highly up-regulated at high growth rates (GR genes from Category 1 experiments, [2])
Summary
Control of growth rate is mediated by tight regulation mechanisms in all free-living organisms since long-term survival depends on adaptation to diverse environmental conditions. At least, it has been found that the expression of the genes that exert significant control over growth rate (high flux control or HFC genes) is not necessarily regulated by growth rate itself. It has not been determined whether the set of HFC genes is the same at all growth rates or whether it is the same in conditions of nutrient limitation or excess. The term “control” has a special meaning in the context of MCA Those cell components that exert control over flux are not necessarily regulatory molecules. We shall routinely use the term ‘growth rate’, rather than ‘flux’, since we have measured differences in growth rate consequent on reducing the copy number of individual genes from two to one in diploid yeast
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