The genetic control of growth rate: a systems biology study in yeast

HFC 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.A 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.Appropriate control of the rate of cell growth is central to the long-term survival of species, particularly microorganisms. A fast growth rate is a competitive advantage when environmental conditions are favourable, while slow growth or even quiescence may allow survival under stress conditions such as rapid changes in the physicochemical environment, starvation, or exposure to toxins. Thus most organisms have evolved stringent controls over the rate of cell growth, and any disruption of these controls has severe consequences; an obvious example being the development of cancer as a result of uncontrolled cell division.Our genome-scale appr