Mechanisms of population dynamics in bacteria — linking gene expression dynamics to individual demographic fates
Final Report Abstract
Evolution and population dynamics are governed by simple demographic events—the survival and reproduction of individuals. Survival and reproduction are known to depend on an individual’s genotype and the environment it experiences. However, even isoclonal individuals raised under highly controlled environments may differ in their demographic fates. Hence, non-genetic and non-environmental variance in phenotypes is expected to drive heterogeneity in demographic fates among individuals. The exploration of this link is at the core of this project. We explored underlying mechanisms that cause such heterogeneity by quantifying gene expression dynamics, and their stochastic and deterministic characteristics, using single-cell bacteria data collected in a microfluidic device and aligned mathematical modelling. We confirm, as predicted, stochastic gene expression dynamics within cells. The stochastic characteristics differ among target genes or chaperones involved in protein folding. We illustrate how asymmetry in gene expression contribute to heterogeneity in growth and division that is observed among mother and daughter bacteria cells. Such gene expression asymmetry builds up already within the mother cell prior to division and increases with age. Other than expected, gene expression signal often does not deterministically increase with age and likely does not explain demographic fates in a simplistic way, though before death stress related gene expression increases. In addition, we advanced mathematical models that link gene expression dynamics—or associated assumed accumulated damage—to demographic fates and population dynamics. Combined we show complex interplay between stochastic and deterministic aspects of asymmetry in gene expression, growth, and aging. In doing so we support findings and provide predictions how evolution influences and is influenced by such neutral heterogeneity. We provide deeper insights into a fundamental aspect of all biological evolution, neutral variability, that links to important applied aspects as among cell heterogeneity in stress response can for instance explain phenotypic resistance to antibiotics that cause clinical treatment failure in humans.
Publications
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Declining old pole physiology gradually enhances gene expression asymmetry in bacteria.
Proenca, Audrey M.; Tuğrul, Murat; Nath, Arpita & Steiner, Ulrich K.
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Demographic Consequences of Damage Dynamics in Single-Cell Ageing.
Tuğrul, Murat & Steiner, Ulrich K.
