title: Noise and Epigenetic Inheritance of Single-Cell Division Times Influence Population Fitness.
abstract: The fitness effect of biological noise remains unclear. For example, even within clonal microbial populations, individual cells grow at different speeds. Although it is known that the individuals' mean growth speed can affect population-level fitness, it is unclear how or whether growth speed heterogeneity itself is subject to natural selection. Here, we show that noisy single-cell division times can significantly affect population-level growth rate. Using time-lapse microscopy to measure the division times of thousands of individual S. cerevisiae cells across different genetic and environmental backgrounds, we find that the length of individual cells' division times can vary substantially between clonal individuals and that sublineages often show epigenetic inheritance of division times. By combining these experimental measurements with mathematical modeling, we find that, for a given mean division time, increasing heterogeneity and epigenetic inheritance of division times increases the population growth rate. Furthermore, we demonstrate that the heterogeneity and epigenetic inheritance of single-cell division times can be linked with variation in the expression of catabolic genes. Taken together, our results reveal how a change in noisy single-cell behaviors can directly influence fitness through dynamics that operate independently of effects caused by changes to the mean. These results not only allow a better understanding of microbial fitness but also help to more accurately predict fitness in other clonal populations, such as tumors.
authors.affiliation: KU Leuven Department Microbiële en Moleculaire Systemen, CMPG Laboratory of Genetics and Genomics, Gaston Geenslaan 1, 3001 Leuven, Belgium; VIB Laboratory of Systems Biology, Gaston Geenslaan 1, 3001 Leuven, Belgium.
authors.forename: Bram
authors.initials: B
authors.lastname: Cerulus
authors.affiliation: KU Leuven Department Microbiële en Moleculaire Systemen, CMPG Laboratory of Genetics and Genomics, Gaston Geenslaan 1, 3001 Leuven, Belgium; VIB Laboratory of Systems Biology, Gaston Geenslaan 1, 3001 Leuven, Belgium; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain; Universitat Pompeu Fabra (UPF), Barcelona 08002, Spain.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: New
authors.affiliation: KU Leuven Department Microbiële en Moleculaire Systemen, CMPG Laboratory of Genetics and Genomics, Gaston Geenslaan 1, 3001 Leuven, Belgium; VIB Laboratory of Systems Biology, Gaston Geenslaan 1, 3001 Leuven, Belgium.
authors.forename: Ksenia
authors.initials: K
authors.lastname: Pougach
authors.affiliation: KU Leuven Department Microbiële en Moleculaire Systemen, CMPG Laboratory of Genetics and Genomics, Gaston Geenslaan 1, 3001 Leuven, Belgium; VIB Laboratory of Systems Biology, Gaston Geenslaan 1, 3001 Leuven, Belgium. Electronic address: kevin.verstrepen@biw.vib-kuleuven.be.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Verstrepen
mesh_terms: D002455:Cell Division / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D056084:Genetic Fitness; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D029701:Saccharomyces cerevisiae Proteins