Engineering topics

Hallatschek, Oskar

Publications and source records attributed to Hallatschek, Oskar.

5 records

DOE OSTI2024

Lineage frequency time series reveal elevated levels of genetic drift in SARS-CoV-2 transmission in England

Genetic drift in infectious disease transmission results from randomness of transmission and host recovery or death. The strength of genetic drift for SARS-CoV-2 transmission is expected to be high due to high levels of superspreading, and this is expected to substantially impact disease epidemiology and evolution. However, we don’t yet have an understanding of how genetic drift changes over time or across locations. Furthermore, noise that results from data collection can potentially confound estimates of genetic drift. To address this challenge, we develop and validate a method to jointly infer genetic drift and measurement noise from time-series lineage frequency data. Our method is highly scalable to increasingly large genomic datasets, which overcomes a limitation in commonly used phylogenetic methods. We apply this method to over 490,000 SARS-CoV-2 genomic sequences from England collected between March 2020 and December 2021 by the COVID-19 Genomics UK (COG-UK) consortium and separately infer the strength of genetic drift for pre-B.1.177, B.1.177, Alpha, and Delta. We find that even after correcting for measurement noise, the strength of genetic drift is consistently, throughout time, higher than that expected from the observed number of COVID-19 positive individuals in England by 1 to 3 orders of magnitude, which cannot be explained by literature values of superspreading. Our estimates of genetic drift suggest low and time-varying establishment probabilities for new mutations, inform the parametrization of SARS-CoV-2 evolutionary models, and motivate future studies of the potential mechanisms for increased stochasticity in this system.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2023

Impact of crowding on the diversity of expanding populations

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.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2022

Self-consistent dispersal puts tight constraints on the spatiotemporal organization of species-rich metacommunities

Dispersal can be critical to the maintenance of ecosystems as it allows local communities to be recolonized after extinction. However, it remains unclear whether the extinction-mitigating effect of dispersal persists when the number of competing species is large. Based on a spatially explicit mathematical description of metacommunities, we show that when many species coexist, each species operates near its extinction threshold, barely surviving due to dispersal. This has general consequences for spatiotemporal abundance patterns. For short-range dispersal, species organize into fractal spatiotemporal extinction patterns characteristic of a directed percolation phase transition. As species approach their extinction threshold, biodiversity is very sensitive to perturbation, suggesting that dispersal within a metacommunity puts tight constraints on the robustness and evolution of species-rich metacommunities. Biodiversity is often attributed to a dynamic equilibrium between the immigration and extinction of species. This equilibrium forms a common basis for studying ecosystem assembly from a static reservoir of migrants—the mainland. Yet, natural ecosystems often consist of many coupled communities (i.e., metacommunities), and migration occurs between these communities. The pool of migrants then depends on what is sustained in the ecosystem, which, in turn, depends on the dynamic migrant pool. This chicken-and-egg problem of survival and dispersal is poorly understood in communities of many competing species, except for the neutral case—the “unified neutral theory of biodiversity.” Employing spatiotemporal simulations and mean-field analyses, we show that self-consistent dispersal puts rather tight constraints on the dynamic migration–extinction equilibrium. When the number of species is large, species are pushed to the edge of their global extinction, even when competition is weak. As a consequence, the overall diversity is highly sensitive to perturbations in demographic parameters, including growth and dispersal rates. When dispersal is short range, the resulting spatiotemporal abundance patterns follow broad scale-free distributions that correspond to a directed percolation phase transition. The qualitative agreement of our results for short-range and long-range dispersal suggests that this self-organization process is a general property of species-rich metacommunities. Our study shows that self-sustaining metacommunities are highly sensitive to environmental change and provides insights into how biodiversity can be rescued and maintained.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2022

Scale-dependent tipping points of bacterial colonization resistance

The commonly observed stability of natural microbiomes is important for their function, yet the ubiquity of microbiome stability remains enigmatic. The strongest form of stability, colonization resistance, protects residents against invaders and is often associated with specific porous structures, such as skin follicles or intestinal crypts. By systematically probing the colonization of fly gut–derived bacteria in microfluidic pores of varying sizes, we revealed that colonization patterns and invasion rates strongly depend on the pore size. Mathematical modeling shows that bacteria spontaneously tend to organize into a dense colonization-resistant state in pores exceeding a critical size. The scale dependence of stability and resilience could bias ecological filtering in microbiomes and should be considered in the design of microbial ecology experiments.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2020

The impact of long-range dispersal on gene surfing

Range expansions lead to distinctive patterns of genetic variation in populations, even in the absence of selection. These patterns and their genetic consequences have been well studied for populations advancing through successive short-ranged migration events. However, most populations harbor some degree of long-range dispersal, experiencing rare yet consequential migration events over arbitrarily long distances. Although dispersal is known to strongly affect spatial genetic structure during range expansions, the resulting patterns and their impact on neutral diversity remain poorly understood. Here, we systematically study the consequences of long-range dispersal on patterns of neutral variation during range expansion in a class of dispersal models which spans the extremes of local (effectively short-ranged) and global (effectively well-mixed) migration. We find that sufficiently long-ranged dispersal leaves behind a mosaic of monoallelic patches, whose number and size are highly sensitive to the distribution of dispersal distances. We develop a coarse-grained model which connects statistical features of these spatial patterns to the evolution of neutral diversity during the range expansion. We show that growth mechanisms that appear qualitatively similar can engender vastly different outcomes for diversity: Depending on the tail of the dispersal distance distribution, diversity can be either preserved (i.e., many variants survive) or lost (i.e., one variant dominates) at long times. Our results highlight the impact of spatial and migratory structure on genetic variation during processes as varied as range expansions, species invasions, epidemics, and the spread of beneficial mutations in established populations.

59 BASIC BIOLOGICAL SCIENCES↗