Bulletin of the American Physical Society
APS March Meeting 2019
Volume 64, Number 2
Monday–Friday, March 4–8, 2019; Boston, Massachusetts
Session A63: Evolutionary and Ecological Dynamics I: EvolutionFocus
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Sponsoring Units: DBIO GSNP Chair: Jeffrey Gore, Massachusetts Institute of Technology Room: BCEC 259A |
Monday, March 4, 2019 8:00AM - 8:36AM |
A63.00001: The role of tolerance in the evolution of antibiotic resistance: from mathematical analysis to observations in the clinic Invited Speaker: Nathalie Balaban The evolution of antibiotic resistance is a fascinating example of the versatility of bacterial evolution, as well as a burning health issue. Resistance mechanisms include efflux pumps that directly lower the intracellular drug concentration, mutations that reduce binding affinity of the drug to its target, enzymes that degrade the drug, etc. These mechanisms result in a decrease of the effective concentration of the antibiotic. However, bacteria were shown to be able to cope with antibiotic treatments that are supposed to kill them also using a different strategy termed “tolerance”. Tolerant bacteria are not able to reduce the concentration of the antibiotic, but to make the duration of the treatment less effective. For example, bacteria that remain transiently dormant during the antibiotic treatment can survive because many different types of antibiotics require active growth to be able to kill. We developed a mathematical and experimental framework to characterize and measure the evolution of tolerance in vitro(1) and in vivo(2). By following the evolution of tolerance and resistance closely, we show that tolerance evolves fast and promotes the subsequent evolution of resistance. Mathematical analysis of the way tolerance promotes the evolution of resistance reveals unexpected routes by which tolerance acts as a stepping stone for the subsequent evolution of resistance. |
Monday, March 4, 2019 8:36AM - 8:48AM |
A63.00002: Enzyme Evolution and Emergence of Novel Catalytic Functions Aditya Ballal, Paul O'Maille, Alexandre V Morozov Enzyme evolution underlies major expansions of metabolic complexity with profound biological implications. In this talk, I will discuss emergence of cyclization reactions catalyzed by terpene synthases. Cyclic terpenes mediate numerous biological functions in modern plants and provide bioactive compounds for human use, including artemisinin, the most effective treatment for malaria currently available. Guided by the available structural, kinetic, and sequence data, we have constructed mutant libraries which include combinations of amino acids responsible for inducing cyclization reactions in an enzyme that produces E beta-farnesene, a linear hydrocarbon chain. We have used measurements of kinetic rates and mass spectrometry in order to assess catalytic efficiency and specificity of the mutant enzymes. Inspired by spin glass models adapted from statistical physics, we have developed a model which predicts properties as a function of enzyme sequence. Using this model we have inferred evolutionary patterns of enzyme energetics. We have also developed a bio-physical model on fitness of an enzyme based on its catalytic properties. Our studies provide quantitative insights into evolutionary dynamics of a major enzyme family, and highlights the importance of epistasis. |
Monday, March 4, 2019 8:48AM - 9:00AM |
A63.00003: Nonlinear dispersal and growth change the phylogenetic structure of expanding populations Gabriel Birzu, Oskar Hallatschek, Kirill Korolev Range expansions have shaped the evolutionary history of many organisms, from microbes to humans. Here, we study how the specifics of growth and dispersal affect the genealogical structure of expanding populations. The genealogical structure plays an important role in fixation of alleles, maintenance of genetic diversity, and genomic inference. Previous studies suggest that genealogies of expanding populations could be nontrivial because organisms at the expansion edge are expected to have an unusually large number of descendants. Indeed, we find these structures can be described by a family of Λ-coalescents, controlled by a single parameter: the ratio between the expansion velocity and the geometric mean of the dispersal and growth rates at low densities. For high values of this ratio, which occur when populations grow or disperse cooperatively, the genealogies are described by a Kingman coalescent. For low values—when the velocity is determined by growth and dispersal at the edge—we find a family of coalescents in which many lineages can merge simultaneously, including the Bolthausen-Sznitman coalescent at one end. These findings show that genealogies in expanding populations have a much richer structure than previously thought. |
Monday, March 4, 2019 9:00AM - 9:12AM |
A63.00004: Coevolution of multiple growth traits in microbial populations under serial dilution Jie Lin, Michael Manhart, Ariel Amir The relative fitness of mutants in a microbial population depends on multiple cellular traits. In the most widely-used evolution experiment protocol, serial dilution (where cells grow, enter stationary phase, and are diluted into a fresh medium), three major traits determining fitness are the growth rate, lag time (the duration of time cells do not grow when exiting stationary phase), and yield (number of cells per unit resource). Here we investigate how these traits coevolve in laboratory evolution experiments using a minimal model of population dynamics, where the only interaction between cells is competition for a single resource. We find that the fixation probability of a beneficial mutation depends on a linear combination of its growth rate and lag time relative to the background strain. The relative selective pressure on growth rate and lag time is set by the dilution factor; for example, a larger dilution factor favors adaptation of growth rate over the adaption of lag time. This result applies equally to the regime of large populations and high mutation rate, where there is abundant clonal interference, as well as the regime of sequential mutations. Moreover, we find an emergent correlation between growth rate and lag time even if mutations have uncorrelated effects. |
Monday, March 4, 2019 9:12AM - 9:24AM |
A63.00005: Rugged landscapes and evolutionary paths to variations in extreme size Thomas Day, Shane Jacobeen, Colin Brandys, William Ratcliff, Peter Yunker The evolutionary transition to multicellularity transformed life on earth, allowing for the evolution of large, complex organisms. While multicellularity can be strongly advantageous, its earliest stages bring unique physical challenges, including the need to mitigate internal and external stresses. Previous work (Jacobeen et.al. Nature Physics 2018 and Jacobeen et.al. PRE 2018) used the model experimental system “snowflake yeast”, a baker’s yeast (S. cerevisiae) genetically modified to remain attached via uncut chitin bonds during mother-daughter budding. However, so far these studies have focused on unimpeded directional selection for large size. Here, we varied the selection protocol to probe the effects of a more complex and rugged fitness landscape on the evolutionary trajectory of nascent multicellular clusters by subjecting the population to external compression prior to selection for larger size. We find that despite this challenge, the maximum cluster size achieved over eight weeks of experimental evolution is unchanged by the presence of compression. This indicates that significant evolutionary changes are possible even under harsh environmental conditions, and that very different selection environments can yield similar phenotypic variation. |
Monday, March 4, 2019 9:24AM - 9:36AM |
A63.00006: Protein evolution under multiple opposing selective forces Erdal Toprak Evolution on a multidimensional adaptive landscape is the rule, not an exception in biological systems. When multiple opposing selection factors are simultaneously present or rapidly fluctuating in an environment, evolution is a genetic search on a convoluted fitness landscape with several pitfalls due to incompatibilities between genetic changes. Using a bacterial membrane protein as a model system, I will address (i) how evolutionary constraints on multiple fitness conditions arranged in a protein sequence and, (ii) how the rate and mechanism of protein evolution can vary under different (opposing or overlapping) selection conditions. |
Monday, March 4, 2019 9:36AM - 9:48AM |
A63.00007: Plastic tradeoffs in evolution: a simple theoretical model Mikhail Tikhonov, Shamit Kachru, Daniel S Fisher Performance tradeoffs are fundamental to evolutionary thinking, but in most models, are simply postulated. This approach is justified for tradeoffs enforced by rigid biophysical or biochemical constraints; unsurprisingly, the best-understood examples are in this class. However, experimental results suggest that many relevant tradeoffs are not rigid, but can themselves evolve. We propose a simple theoretical framework for studying how an evolving tradeoff structure both shapes and is shaped by the evolutionary trajectory. We show that this feedback loop naturally leads to non-intuitive behaviors. For instance, although strongly diverging tasks might be expected to result in stronger tradeoffs, evolution can reverse this trend. We also show that within our model, pre-evolving a genome in one environment can predictably impede or facilitate its subsequent speed of adaptation in another. Our results extend previous work relating modularity and “evolvability” to a more general discussion of flexible tradeoff architectures and their impact on evolutionary dynamics. |
Monday, March 4, 2019 9:48AM - 10:00AM |
A63.00008: Homologous recombination rates of bacteria Edo Kussell Bacteria can take up DNA from their environment and incorporate it into their genomes using various recombination mechanisms. To quantify recombination rates in different environments requires a robust method that operates efficiently using large scale sequencing datasets. In this talk, I present such a method, based on exact solutions of population genetic models, and apply it in a wide range of bacteria. |
Monday, March 4, 2019 10:00AM - 10:12AM |
A63.00009: Tuning Spatial Profiles of Selection Pressure to Modulate the Evolution of Drug Resistance Max De Jong, Kevin Wood Spatial heterogeneity plays an important role in the evolution of drug resistance, but relatively little is known about resistance in complex spatial profiles of selection pressure. Here we use a toy model of stochastic microbial dynamics to investigate how different spatial profiles of selection pressure impact the time to fixation of a resistant allele. Using mean first passage time calculations, we show that spatial heterogeneity accelerates resistance evolution when the rate of spatial migration is sufficiently large relative to mutation but slows fixation for small migration rates. We also demonstrate that optimal tuning of the spatial profile can dramatically slow the spread and fixation of resistant subpopulations, even in the absence of a fitness cost for resistance. Finally, we incorporate a fitness cost associated with the resistant allele and observe that the intermediate regime in which spatial heterogeneity can speed or slow resistance is much larger and the effect of heterogeneity can be greatly amplified. Our results may lay the groundwork for optimized, spatially resolved drug dosing strategies for mitigating the effects of drug resistance. |
Monday, March 4, 2019 10:12AM - 10:24AM |
A63.00010: Evolutionarily stable strategies in dynamic population models with applications to bird migration Samuel Cho, Simon Levin Dynamic state variable models have been widely used to understand individual animal behaviors.1 However, when a population is studied, frequency-dependence and density-dependence often provide incentives to switch strategies, which are not captured in traditional dynamic models. In the discrete states and discrete time problem, we have a coupled forward-backward system, solution of which gives the evolutionarily stable policies determining the strategies for a given state. With the recent development of mean field game theory2, we can find general ecological conditions under which evolutionarily stable policies exist, and can be numerically found. We will also apply the results to understand various strategies during bird migration, such as choice of intermediate sites, foraging rates, and timing of arrival. |
Monday, March 4, 2019 10:24AM - 10:36AM |
A63.00011: Environmental heterogeneity limits the action of selection Matti Gralka, Oskar Hallatschek Evolutionary dynamics is fundamentally shaped by stochastic processes: mutations enter populations randomly, and the fate of a mutant lineage is determined by the competition between (random) genetic drift and (deterministic) selection. In populations undergoing range expansions, fluctuations in the reproductive process and the local motion of individuals are enhanced within a small subpopulation at the edge of the population. Geographical heterogeneities could therefore have a dramatic impact on evolutionary dynamics if they shape the local advance of the population front. |
Monday, March 4, 2019 10:36AM - 10:48AM |
A63.00012: The Replicator Dynamics for Multilevel Selection in Evolutionary Games Daniel Cooney We consider a stochastic model for evolution of cooperation in the Prisoner's Dilemma played in group-structured populations. Selection operates at two levels: individuals compete with individuals in their group, while groups compete with other groups. In the limit of infinite population size, we derive a non-local PDE describing the probability distribution of groups in the population. We characterize the long-time behavior of our system, with an emphasis on understanding the most frequent group compositions at steady state. |
Monday, March 4, 2019 10:48AM - 11:00AM |
A63.00013: Evolution of weak cooperative interactions for biological specificity Ang Gao, Krishna Shrinivas, Paul Lepeudry, Hiroshi I Suzuki, Phillip Sharp, Arup K Chakraborty A hallmark of biological systems is that particular functions and outcomes are realized in specific contexts, such as when particular signals are received. One mechanism for mediating specificity is described by Fisher’s “lock and key” metaphor, exemplified by enzymes that bind selectively to a particular substrate via specific finely tuned interactions. Another mechanism relies on multivalent weak cooperative interactions. Its importance has recently been illustrated by the recognition that liquid-liquid phase transitions underlie the formation of membraneless condensates that perform specific cellular functions. Based on computer simulations of an evolutionary model, we report that the latter mechanism likely became evolutionarily prominent when a large number of tasks had to be performed specifically for organisms to function properly. We find that the emergence of weak cooperative interactions makes organisms more evolvable. Specificity mediated by weak cooperative interactions results in some useful cross-reactivity, but also increases susceptibility to mis-regulation. |
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