A theory of evolutionary dynamics on any complex population structure reveals stem cell niche architecture as a spatial suppressor of selection.

Yang Ping Kuo, C��sar Nombela-Arrieta, Oana Carja
Author Information
  1. Yang Ping Kuo: Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, USA.
  2. C��sar Nombela-Arrieta: Department of Medical Oncology and Hematology, University and University Hospital Zurich, Zurich, Switzerland. ORCID
  3. Oana Carja: Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, USA. oana@cmu.edu. ORCID

Abstract

How the spatial arrangement of a population shapes its evolutionary dynamics has been of long-standing interest in population genetics. Most previous studies assume a small number of demes or symmetrical structures that, most often, act as well-mixed populations. Other studies use network theory to study more heterogeneous spatial structures, however they usually assume small, regular networks, or strong constraints on the strength of selection considered. Here we build network generation algorithms, conduct evolutionary simulations and derive general analytic approximations for probabilities of fixation in populations with complex spatial structure. We build a unifying evolutionary theory across network families and derive the relevant selective parameter, which is a combination of network statistics, predictive of evolutionary dynamics. We also illustrate how to link this theory with novel datasets of spatial organization and use recent imaging data to build the cellular spatial networks of the stem cell niches of the bone marrow. Across a wide variety of parameters, we find these networks to be strong suppressors of selection, delaying mutation accumulation in this tissue. We also find that decreases in stem cell population size also decrease the suppression strength of the tissue spatial structure.

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Grants

  1. R35 GM147445/NIGMS NIH HHS
  2. T32 EB009403/NIBIB NIH HHS
  3. R35GM147445/U.S. Department of Health & Human Services | National Institutes of Health (NIH)

MeSH Term

Algorithms
Biological Evolution
Stem Cell Niche
Genetics, Population
Selection, Genetic
Humans
Mutation
Animals
Bone Marrow
Computer Simulation

Word Cloud

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