yangpingkuo / suppressor-of-selection-in-the-stem-cell-niches-of-the-bone-marrow

Understanding 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 connected by migration corridors, symmetrical structures that most often act as well-mixed populations. Other studies use networks to model the more complex topologies of natural populations and to study the structures that suppress or amplify selection. However, they usually assume either very small networks, large but regular networks, or strong constraints on the strength of selection considered. Here we build network generation algorithms, evolutionary simulations and derive general analytic approximations for probabilities of fixation in populations with complex spatial structure. By tuning network parameters and properties independent of each other, we build a unifying evolutionary theory across network families and show that both a network's degree distribution, as well as its node mixing pattern shape the evolutionary dynamics of new mutations. We also write the relevant selective parameter, a combination of network statistics, predictive of evolutionary dynamics. We 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 and regardless of the birth death process used, 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.