Biology subjects

Oskar Hallatschek

Publications and source records attributed to Oskar Hallatschek.

3 recordsLinked to original sources

bioRxiv2016

Excess of mutational jackpot events in growing populations due to gene surfing

One of the hallmarks of spontaneous mutations in growing populations is the emergence of mutational jackpot events - large mutant clones arising from mutations that by chance occur early in the development of a cellular population so that their progenitors benefit from prolonged growth. Due to their sheer size, these jackpot events, first discovered by Luria and Delbruck [1], are thought to have momentous roles in short-term evolutionary processes, including the adaptation from standing variation [2-4], evolutionary rescue [5], drug resistance evolution [6-10], and the somatic evolution of genetic diseases [11, 12]. However, because the emergence of jackpot events has been understood only in uniformly growing populations [1, 10, 13], it is currently impossible to predict their impact on the evolution of many naturally structured populations. To study jackpot events in spatially structured populations, we tracked mutant clones in microbial populations using fluorescent microscopy and population sequencing. High-frequency mutations were massively enriched in microbial colonies compared to well-shaken liquid cultures, as a result of late-occurring mutations surfing at the edge of range expansions [14-16]. We provide a mathematical theory that explains the observed excess of jackpot events and predicts their role in promoting rare evolutionary outcomes. In particular, we show that resistant clones generated by surfing can become unleashed under high selection pressures, and thus represent a drug resistance hazard for high-dose drug treatments. An excess of mutational jackpot events is shown to be a general consequence of non-uniform growth and, therefore, could be relevant to the mutational load of developing biofilm communities, solid tumors and multi-cellular organisms.

Evolutionary Biology↗

bioRxiv2016

Self-driven jamming in growing microbial populations

In natural settings, microbes tend to grow in dense populations [1-4] where they need to push against their surroundings to accommodate space for new cells. The associated contact forces play a critical role in a variety of population-level processes, including biofilm formation [5-7], the colonization of porous media [8, 9], and the invasion of biological tissues [10-12]. Although mechanical forces have been characterized at the single cell level [13-16], it remains elusive how collective pushing forces result from the combination of single cell forces. Here, we reveal a collective mechanism of confinement, which we call self-driven jamming, that promotes the build-up of large mechanical pressures in microbial populations. Microfluidic experiments on budding yeast populations in space-limited environments show that self-driven jamming arises from the gradual formation and sudden collapse of force chains driven by microbial proliferation, extending the framework of driven granular matter [17-20]. The resulting contact pressures can become large enough to slow down cell growth by delaying the cell cycle in the G1 phase and to strain or even destroy the microenvironment through crack propagation. Our results suggest that self-driven jamming and build-up of large mechanical pressures is a natural tendency of microbes growing in confined spaces, contributing to microbial pathogenesis and biofouling [21-26].

Microbiology↗

bioRxiv2016

Allele Surfing Promotes Microbial Adaptation from Standing Variation

The coupling of ecology and evolution during range expansions enables mutations to establish at expanding range margins and reach high frequencies. This phenomenon, called allele surfing, is thought to have caused revolutions in the gene pool of many species, most evidently in microbial communities. It has remained unclear, however, under which conditions allele surfing promotes or hinders adaptation. Here, using microbial experiments and simulations, we show that, starting with standing adaptive variation, range expansions generate a larger increase in mean fitness than spatially uniform population expansions. The adaptation gain results from soft selective sweeps emerging from surfing beneficial mutations. The rate of these surfing events is shown to sensitively depend on the strength of genetic drift, which varies among strains and environmental conditions. More generally, allele surfing promotes the rate of adaptation per biomass produced, which could help developing biofilms and other resource-limited populations to cope with environmental challenges.

Evolutionary Biology↗