RT Journal Article
SR Electronic
T1 Physical interactions reduce the power of natural selection in growing yeast colonies
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 332700
DO 10.1101/332700
A1 Andrea Giometto
A1 David R Nelson
A1 Andrew W Murray
YR 2018
UL http://biorxiv.org/content/early/2018/09/14/332700.abstract
AB Microbial populations often assemble in dense populations in which proliferating individuals exert mechanical forces on the nearby cells. Here, we use yeast strains whose doubling times depend differently on temperature to show that physical interactions among cells affect the competition between different genotypes in growing yeast colonies. Our experiments demonstrate that these physical interactions have two related effects: they cause the prolonged survival of slower-growing strains at the actively-growing frontier of the colony and cause faster-growing strains to increase their frequency more slowly than expected in the absence of physical interactions. These effects also promote the survival of slower-growing strains and the maintenance of genetic diversity in colonies grown in time-varying environments. A continuum model inspired by overdamped hydrodynamics reproduces the experiments and predicts that the strength of natural selection depends on the width of the actively-growing layer at the colony frontier. We verify these predictions experimentally. The reduced power of natural selection observed here may favor the maintenance of drug-resistant cells in microbial populations and could explain the apparent neutrality of inter-clone competition within tumors.Significance Statement Microbes often live in dense populations such as colonies and biofilms. We show that the success and extinction of yeast strains within a growing colony are determined by a combination of their relative fitness and the forces exerted by proliferating cells on their neighbors. These physical interactions prolong the survival of less-fit strains at the growing frontier of the colony and slow down the colony’s takeover by fitter strains. This reduction in the power of natural selection favors the maintenance of genetic diversity in environments in which the strains’ relative growth rates vary with time. Growth-induced physical interactions may thus favor the maintenance of drug-resistant cells, which are typically less-fit than non-resistant cells, within dense microbial populations.Author contributionsA.G., D.R.N., A.W.M. designed the research and wrote the paper, A.G. performed the research and analyzed the data.