Crowding effects are key to the self-organization of densely packed cellular assemblies, such as biofilms, solid tumors, and developing tissues. When cells grow and divide they push each other apart, remodeling the structure and extent of the populations range. It has recently been shown that crowding effects also couple the evolutionary fate of neighboring cells, thereby weakening the strength of natural selection. However, the impact of crowding on neutral processes remains unclear. Here, we quantify the genetic diversity of expanding microbial colonies and uncover signatures of crowding in the site frequency spectrum. By combining fluctuation tests, cell-based simulations, and lineage tracing in a novel microfluidic incubator, we find that the majority of mutations arise behind the expanding frontier, giving rise to clones that are mechanically "pushed out" of the growing region by the proliferating cells in front. These excluded-volume interactions result in a clone size distribution that solely depends on where the mutation first arose relative to the front and is characterized by a simple power-law for sizes below a critical threshold. Our model and simulations predict that the distribution only depends on a single parameter, the characteristic growth layer thickness, and hence allows estimation of the mutation rate in a variety of crowded cellular populations. Combined with previous studies on high-frequency mutations, our finding provides a unified picture of the genetic diversity in expanding populations over the whole frequency range and suggests a practical method to assess growth dynamics by sequencing populations across scales.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.