Bulletin of the American Physical Society
APS March Meeting 2022
Volume 67, Number 3
Monday–Friday, March 14–18, 2022; Chicago
Session W05: Ecological and Evolutionary Dynamics VFocus Recordings Available
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Sponsoring Units: DBIO Chair: Daniel Weissman, Emory Room: McCormick Place W-178A |
Thursday, March 17, 2022 3:00PM - 3:36PM |
W05.00001: Sequence-affinity landscapes and the evolution of broadly neutralizing anti-influenza antibodies Invited Speaker: Michael Desai
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Thursday, March 17, 2022 3:36PM - 3:48PM |
W05.00002: Higher accuracy due to higher speeds in copying information Riccardo Ravasio, Kabir B Husain, Marco Ribezzi-Crivellari, Arvind Murugan Biological information in molecules such as DNA must be copied with both accuracy and speed to be transmitted across generations. Numerous theories have quantified how higher accuracy can be attained at the cost of speed. However, experimental data often shows the opposite trade-off: mutations in proofreading DNA polymerases that increase mutation rates generally reduce speed or processivity. We show how such counter-intuitive trade-offs result from well-studied non-equilibrium proofreading models combined with stalling effects and evolutionary reasoning about the impact of typical mutations. We derive conditions under which proofreading mechanisms can evolve under selection for higher speed alone, without any pressure to reduce mutation rates. Such a relationship has evolutionary consequences, ranging from the origin of life in the RNA world to the evolution of mutation rates in extant populations. |
Thursday, March 17, 2022 3:48PM - 4:00PM |
W05.00003: Evolution of mutation rates is determined by short term costs and long term benefits in proofreading polymerases Vedant Sachdeva, Kabir B Husain, Riccardo Ravasio, Wanqiang Liu, Benjamin H Good, Arvind Murugan The nature of evolution is subject to evolution itself, through changes in modifier traits such as mutation and recombination rates. Mutation rate modifiers ("mutators") are frequently observed in both natural and experimental populations of microbes. However, little is known about the biophysical constraints that shape their long-term evolution. Here we study the evolution of mutation rates in proofreading polymerases using a self-replicating plasmid system in yeast. We find that a reversal of the classical speed-accuracy trade-off implies that mutator polymerases have distinct fitnesses on different timescales: variants leading to high mutation rates confer a long term benefit for their lineage but are often selected against in the short term due to their lower processivity. We determine the range of environmental conditions that select for mutators in the context of such biophysical constraints, and demonstrate that varying environments over time can select for mutators even when no static intermediate environments can. These results show how pleiotropic biophysical interactions between short- and long-term fitness can alter modifier selection in unexpected ways. |
Thursday, March 17, 2022 4:00PM - 4:12PM |
W05.00004: Signatures of an evolutionary capacitor from a high-resolution Luria-Delbruck assay Kabir B Husain, David Pincus, Arvind Murugan Pre-existing genetic diversity drives adaptation, but the factors that determine standing genetic variation in a population remain poorly understood. The chaperone Hsp90 has been proposed to act as an `evolutionary capacitor': buffering the deleterious impact of new mutations and allowing them to persist in a population. Yet, the scope and magnitude of such buffering remains unknown. Here, we generalise the assay of Luria and Delbruck to probe Hsp90's role in the acquisition of antibiotic resistance by \textit{S. cerevisiae}. Resistance mutations buffered by Hsp90 can arise early and grow to a `jackpot' of mutants, with a corresponding long-tail in the Luria-Delbruck distribution. In contrast, when Hsp90 is compromised, early mutations are selected against and the tail of distribution is truncated. We complement our statistical results with a targeted mutation-accumulation assay. Overall, our results suggest how cellular processes can dictate the ebb and flow of genetic diversity in a population. |
Thursday, March 17, 2022 4:12PM - 4:24PM |
W05.00005: Inferring epistasis from deep mutational scanning data Zhenchen Hong, John P Barton Understanding the mutational effects of genetic variants is an important subject in evolutionary biology. Deep mutational scanning (DMS) is a popular mutagenesis method assisting to measure the functional effects of genetic variants at very large scales. However, current state-of-the-art methods for analyzing DMS data can provide inconsistent results across experimental replicates, and the inference of epistasis remains a particular technical challenge. Here, we present a method drawing on previous theoretical advances in population genetics [1] to interpret not only the functional effects of single genetic variants but also the epistasis effects from DMS data. With extensive tests, our analysis reveals more consistent inference of mutational effects across experimental replicates compared to current methods. We also find interpretable epistatic interactions between genetic variants. Our framework can be widely applied to DMS data with multiple generations, replicates, and conditions. |
Thursday, March 17, 2022 4:24PM - 4:36PM |
W05.00006: Dynamics of bacterial recombination in the human gut microbiome Zhiru Liu, Benjamin H Good Horizontal gene transfer is a ubiquitous force in microbial evolution. Previous studies have shown that the human gut is a hot spot for gene transfer between species. However, the more subtle exchange of DNA within species, better known as "recombination," is less well characterized in this ecosystem. Rates of recombination are often inferred using parametric approaches that leverage simple null models from population genetics. These models often omit key factors like natural selection and population structure, which can alter signatures of recombination among contemporary DNA sequences. In this talk, we will show how the broad range of timescales within the human gut microbiota provides new opportunities to measure individual recombination events directly, leveraging nonparametric approaches that require minimal population genetic assumptions. These methods enable quantitative comparisons of recombination across a range of phylogenetically diverse species, which highlight general regions of "phase space" that could benefit from future theoretical exploration. |
Thursday, March 17, 2022 4:36PM - 4:48PM |
W05.00007: Core genes can have higher recombination rates than accessory genes within global microbial populations Asher Preska Steinberg, Mingzhi Lin, Edo Kussell Recombination is essential to microbial evolution, and is involved in the spread of antibiotic resistance, antigenic variation, and adaptation to the host niche. However, quantifying the impact of homologous recombination on different gene classes, which is critical to understanding how selection acts on variation to shape species diversity and genome structure, remains challenging due to the complex phylogenetic relationships of bacterial genomes. Here, we apply a non-phylogenetic approach to infer homologous recombination rates in the core and accessory genome (genes present in all strains and only a subset of strains, respectively) using >100,000 whole genome sequences from 12 microbial species. By sampling discrete sets of sequence clusters, we find global gene pools are remarkably interconnected despite biogeographic boundaries, which has implications for how population structure influences evolutionary trajectories. We show that in a majority of species, core genes have shorter coalescence times and higher recombination rates than accessory genes, and that gene frequency is often positively correlated with recombination. Our results indicate that homologous recombination may play a key role in increasing the efficiency of selection in critical gene classes. |
Thursday, March 17, 2022 4:48PM - 5:00PM |
W05.00008: Hybridization driven by selection is a major source of genetic diversity in a natural bacterial population Gabriel Birzu, Devaki Bhaya, Daniel S Fisher The traditional view of bacterial evolution is that populations form distinct genetic clusters within a narrow ecological niche, with limited recombination between closely related individuals. However, recent evidence from deep sequencing of microbial populations suggests an alternative view in which frequent recombination leads to bacteria evolving as large quasi-sexual populations [1]. Which of these views best approximates natural bacterial populations remains unresolved. |
Thursday, March 17, 2022 5:00PM - 5:12PM |
W05.00009: Eco-evolutionary response of complex ecosystems to changing environments Jim Wu, David J Schwab, Anne-Florence Bitbol Although ecological and evolutionary dynamics have long been assumed to occur on disparate timescales, many complex ecosystems, especially microbial communities, show rapid adaptation in response to environmental changes. These species with novel phenotypic traits construct new niches, which in turn alters the environment. We explore this eco-evolutionary feedback via a consumer-resource model to account for evolution. Specifically, consumers compete for resources, experience demographic noise, and mutate in a phenotypic trait space. Since the interactions between consumers and resources are asymmetric, the ecosystem relaxes towards a non-equilibrium steady state where the community structure is constantly changing. Drawing from non-equilibrium statistical physics, we analyze the properties of this non-equilibrium steady state and discuss the new phases and behaviors that an ecosystem with concurrent ecological and evolutionary timescales can exhibit. Furthermore, we investigate the response of a complex community to changes in resource influx and how the rate of adaptation is affected by a time-varying environment. |
Thursday, March 17, 2022 5:12PM - 5:24PM |
W05.00010: Effects of light and nutrients on the growth of algal cells revealed by a microfluidic platform Fangchen Liu, Larissa Gaul, Mohammad Yazdani, Beth A Ahner, Mingming Wu Photosynthetic micro-organisms play important roles in shaping and balancing aquatic ecosystems. One emerging environmental problem caused by these organisms is Harmful Algal Bloom (HAB), where the sudden growth of cyanobacterium or microalga disrupts lake or coastal ecosystems. In order to elucidate the effects of complex environmental conditions (physical, chemical, and biological) under which HABs occur, we developed a micro-scale light gradient generator, which, together with a microfluidics chemical gradient generator, enabled the quantitative study of algal growth under various environmental cues. In this presentation, we systematically studied the growth kinetics of Chlamydomonas reinhardtii, under a light intensity gradient, a nitrogen (N) concentration gradient, and combined light and N gradients. The combinatory effect of light and N on algal growth shed light on the investigation into the interplay between photosynthesis and nitrogen metabolism. Our work revealed that the growth rate of the microalgae was significantly regulated by the light intensity and nitrogen concentration, and demonstrated the enabling ability of the platform in fast screening of environmental factors for algal growth. |
Thursday, March 17, 2022 5:24PM - 5:36PM |
W05.00011: Acetate inhibits bacterial growth by shrinking the metabolite pool size Brian R Taylor, Vadim Patsalo, Joshua D Rabinowitz, Yihui Shen, Terence T Hwa, Hiroyuki Okano, James Williamson, Zhongge Zhang Acetate, propionate, and butyrate are short-chain fatty acids (SCFA) that accumulate to high concentrations in the mammalian gut and other environments dominated by fermentation. These SCFAs acidify the growth environment and inhibit the growth of many different types of bacteria. However, despite the ubiquity of this problem, bacterial strategy resisting SCFA stress is unclear. Here we present a quantitative physiological study of E. coli under acetate stress, complemented by proteomic and metabolomic analysis. The results reveal growth inhibition arises from two orthogonal factors: reduced internal pH and massive accumulation of acetate in the cytoplasm. The acetate accumulation in particular reduces growth by acting as a “useless metabolite” which excludes other metabolites. Further, we establish that cells balance the problem presented by these two stresses by optimizing their internal pH to minimize acetate accumulation. As adaptation to both factors requires changes to protein properties at the genome scale, gut microbes are forced to choose between growing fast at neutral pH or tolerating SCFAs at low pH, phenotypes evolved by the two major phyla Bacteroidetes and Firmicutes, respectively, in the gut. |
Thursday, March 17, 2022 5:36PM - 5:48PM |
W05.00012: Population dynamics of mitochondrial genomes in Saccharomyces cerevisiae reveal tightly constrained mutational trajectories and a simple relationship between genome content and replicative fitness Christopher Nunn, Sidhartha Goyal Mitochondrial genome (mtDNA) quality is important for cellular function. Eukaryotic cells contain numerous copies of mtDNA which allows for the coexistence of mutant and wild-type mtDNA in individual cells. The fate of these mutant mtDNA depends on their relative replicative fitness as compared to the wild-type genomes. Yet the dynamics of the generation mutant mtDNA as well as their fitness to outcompete wild-type mtDNA remain to be fully understood. The primary challenge has been to track the large structural mutations that alter wild-type mtDNA. To address this, we utilize long read single-molecule sequencing to track the mutational trajectories of mtDNA in Saccharomyces cerevisiae (budding yeast). We show a previously unseen pattern that constrains the mtDNA mutational landscape where new mutations are contingent on previous events. We then propose a phenomenological model of relative fitness – the measure of the replication advantage of mutant genomes over wild-type genomes which depends on biophysical parameters of mutant mtDNA. Finally, we test how well the model explains relative fitness by performing direct competition between mutant and wild-type mtDNA in yeast mating experiments. |
Thursday, March 17, 2022 5:48PM - 6:00PM |
W05.00013: Spontaneous mutations emerge as drivers of de novo gene birth in a minimal evolutionary model Somya Mani, Tsvi Tlusty
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