Datensatz

Zusammenfassung

Crowding effects critically impact 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
population’s range. Recent work has shown that crowding has a strong impact on the
strength of natural selection. However, the impact of crowding on neutral processes,
which controls the fate of new variants as long as they are rare, remains unclear. Here, we
quantify the genetic diversity of expanding microbial colonies and uncover signatures
of crowding in the site frequency spectrum. By combining Luria–Delbrück fluctuation
tests, lineage tracing in a novel microfluidic incubator, cell-based simulations, and
theoretical modeling, 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 low-frequency clones. Our
model predicts that the distribution 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 spatial scales