From single-cell variability to population growth

How does cell-to-cell variability affect the population growth rate? The answer to this question will determine whether evolution will tend to suppress or enhance fluctuations. We revisited this long-standing problem, considering realistic models where cell size is controlled. We found that this profoundly affects the results, and in contrast to the dogma in the field, found that single-cell variability is often detrimental rather than beneficial to the population growth. In other scenarios, population diversity results from the asymmetric segregation of cellular resources. We discovered a phase transition between a regime where homogeneity is optimal to one where asymmetric division is favorable. Drawing on ideas from statistical physics allowed us to develop novel techniques for inferring fundamental information regarding growth from single-cell data, in particular extracting the population growth rate from single lineages. Surprisingly, this problem elegantly connects to Large Deviation Theory, the non-equilibrium generalization of equilibrium statistical physics.

Relevant publications:

  • Jie Lin and Ariel Amir, The Effects of Stochasticity at the Single-Cell Level and Cell Size Control on the Population Growth, Cell Systems 5, 358–367 (2017).
  • Jie Lin and Ariel Amir, From single-cell variability to population growth, Physical Review E 101, 012401 (2020).
  • Ethan Levien, Jane Kondev and Ariel Amir, The interplay of phenotypic variability and fitness in finite microbial populations, Journal of the Royal Society Interface 17, 20190827 (2020).
  • Jie Lin, Jiseon Min and Ariel Amir, Optimal segregation of proteins: phase transitions and symmetry breaking, Physical Review Letters 122, 068101 (2019).
  • Ethan Levien, Trevor GrandPre and Ariel Amir, Large Deviation Principle Linking Lineage Statistics to Fitness in Microbial Populations, Physical Review Letters 125, 048102 (2020).
  • Felix Barber, Jiseon Min, Andrew W. Murray and Ariel Amir, Modeling the impact of single-cell stochasticity and size control on the population growth rate in asymmetrically dividing cells, PLOS Computational Biology 17, e1009080 (2021).
  • Ethan Levien, Jiseon Min, Jane Kondev and Ariel Amir, Non-genetic variability in microbial populations: survival strategy or nuisance?, Reports on Progress in Physics 84, 116601 (2021).
  • Trevor GrandPre, Ethan Levien and Ariel Amir, Extremal events dictate population growth rate inference, arXiv preprint arXiv:2501.08404 (2025).
  • Ethan Levien, Joon Ho Kang, Krishanu Biswas, Scott R. Manalis, Ariel Amir and T. Petteri Miettinen, Stochasticity in mammalian cell growth rates drives cell-to-cell variability independently of cell size and divisions, bioRxiv (2025).