Genetic and nongenetic determinants of cell growth variation assessed by high-throughput microscopy

Research output: Contribution to journalArticle

Abstract

In microbial populations, growth initiation and proliferation rates are major components of fitness and therefore likely targets of selection. We used a high-throughput microscopy assay, which enables simultaneous analysis of tens of thousands of microcolonies, to determine the sources and extent of growth rate variation in the budding yeast (Saccharomyces cerevisiae) in different glucose environments. We find that cell growth rates are regulated by the extracellular concentration of glucose as proposed by Monod (1949), but that significant heterogeneity in growth rates is observed among genetically identical individuals within an environment. Yeast strains isolated from different geographic locations and habitats differ in their growth rate responses to different glucose concentrations. Inheritance patterns suggest that the genetic determinants of growth rates in different glucose concentrations are distinct. In addition, we identified genotypes that differ in the extent of variation in growth rate within an environment despite nearly identical mean growth rates, providing evidence that alleles controlling phenotypic variability segregate in yeast populations. We find that the time to reinitiation of growth (lag) is negatively correlated with growth rate, yet this relationship is strain-dependent. Between environments, the respirative activity of individual cells negatively correlates with glucose abundance and growth rate, but within an environment respirative activity and growth rate show a positive correlation, which we propose reflects differences in protein expression capacity. Our study quantifies the sources of genetic and nongenetic variation in cell growth rates in different glucose environments with unprecedented precision, facilitating their molecular genetic dissection.

Original languageEnglish (US)
Pages (from-to)2568-2578
Number of pages11
JournalMolecular Biology and Evolution
Volume30
Issue number12
DOIs
StatePublished - Dec 2013

Fingerprint

microscopy
Microscopy
cell growth
glucose
Growth
yeasts
Glucose
yeast
molecular genetics
Saccharomyces cerevisiae
inheritance (genetics)
population growth
protein synthesis
Yeasts
alleles
Geographic Locations
Inheritance Patterns
dissection
Saccharomycetales
genotype

Keywords

  • clonal heterogeneity
  • glucose deprivation
  • growth rate
  • lag duration
  • natural variation
  • respiro-fermentative growth
  • Saccharomyces cerevisiae
  • single cell

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics

Cite this

Genetic and nongenetic determinants of cell growth variation assessed by high-throughput microscopy. / Ziv, Naomi; Siegal, Mark; Gresham, David.

In: Molecular Biology and Evolution, Vol. 30, No. 12, 12.2013, p. 2568-2578.

Research output: Contribution to journalArticle

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