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Ascensao, J. A.

Publications and source records attributed to Ascensao, J. A..

6 recordsLinked to original sources

The evolution of genetic drift over 50,000 generations

Random variation in reproductive success-genetic drift-profoundly shapes genetic diversity and evolutionary trajectories. The strength of drift depends on the variance in descendant number, [Formula], which governs key evolutionary outcomes: for instance, the establishment probability of a beneficial mutation scales inversely with [Formula]. However, whether [Formula] itself evolves over long timescales has remained unclear, because allele-frequency fluctuations depend on drift only through the effective population size, [Formula], which blends census population size with descendant-number variance. Here, we disentangle these components by using model-based Bayesian inference combined with joint tracking of (i) frequency fluctuations of neutrally barcoded lineages and (ii) census population sizes across growth cycles in theE. coliLong-Term Evolution Experiment (LTEE). Analyzing 33 clones spanning the ancestor through 50,000 generations in two replicate populations (Ara-2 and Ara+2), we find that the strength of genetic drift evolved markedly-and divergently-between the two replicate populations. Both census size and [Formula] changed substantially through time, with most variation in Ne driven by shifts in [Formula] rather than census size. After approximately 2,000 generations, the [Formula] of the two populations diverged sharply: Ara+2 generally remained close to a bottleneck-only null expectation, whereas Ara-2 exhibited 1.5-5x stronger drift, consistent with an evolved increase in stochasticity during growth. These results imply that mutations can alter both the mean and the variance of the descendant-number distribution, and we show that the joint distribution of mutational effects on fitness and on [Formula] can substantially modulate the rate of adaptation. The key parameter governing genetic drift can therefore itself evolve in the LTEE, with direct consequences for adaptation.

evolutionary biology↗

Frequency-dependent fitness effects are ubiquitous

In simple microbial populations, the fitness effects of selected mutations are typically assumed to be constant, regardless of mutant frequency. This assumption underpins predictions about evolutionary dynamics, epistasis, and the maintenance of genetic diversity. Here, we systematically test this assumption using beneficial mutations from early generations of the Escherichia coli Long-Term Evolution Experiment (LTEE). Using flow cytometry-based competition assays, we find that frequency-dependent fitness effects are the norm rather than the exception, occurring in approximately 80% of strain pairs tested. Most competitions exhibit negative frequency-dependence, where fitness advantages decline as mutant frequency increases. We demonstrate that the strength of frequency-dependence is predictable from invasion fitness measurements, which explain approximately half of the biological variation in frequency-dependent slopes. We also observe violations of fitness transitivity in several strain combinations, indicating that competitive outcomes cannot always be predicted from fitness measured against a single reference strain. High-resolution measurements reveal that frequency-dependence changes substantially within the growth cycle, with the net per-cycle effect reflecting the balance of opposing dynamics at different growth phases. Our results demonstrate that even in a model system designed to minimize ecological complexity, subtle interactions between closely related genotypes create frequency-dependent selection that can fundamentally alter evolutionary trajectories.

evolutionary biology↗

Asynchronous abundance fluctuations can drive giant genotype frequency fluctuations

Large stochastic population abundance fluctuations are ubiquitous across the tree of life1-7, impacting the predictability of population dynamics and influencing eco-evolutionary outcomes. It has generally been thought that these large abundance fluctuations do not strongly impact evolution, as the relative frequencies of alleles in the population will be unaffected if the abundance of all alleles fluctuate in unison. However, we argue that large abundance fluctuations can lead to significant genotype frequency fluctuations if different genotypes within a population experience these fluctuations asynchronously. By serially diluting mixtures of two closely related E. coli strains, we show that such asynchrony can occur, leading to giant frequency fluctuations that far exceed expectations from models of genetic drift. We develop a flexible, effective model that explains the abundance fluctuations as arising from correlated offspring numbers between individuals, and the large frequency fluctuations result from even slight decoupling in offspring numbers between genotypes. This model accurately describes the observed abundance and frequency fluctuation scaling behaviors. Our findings suggest chaotic dynamics underpin these giant fluctuations, causing initially similar trajectories to diverge exponentially; subtle environmental changes can be magnified, leading to batch correlations in identical growth conditions. Furthermore, we present evidence that such decoupling noise is also present in mixed-genotype S. cerevisiae populations. We demonstrate that such decoupling noise can strongly influence evolutionary outcomes, in a manner distinct from genetic drift. Given the generic nature of asynchronous fluctuations, we anticipate that they are widespread in biological populations, significantly affecting evolutionary and ecological dynamics.

evolutionary biology↗

Rediversification Following Ecotype Isolation Reveals Hidden Adaptive Potential

Microbial communities play a critical role in ecological processes, and their diversity is key to their functioning. However, little is known about if communities can regenerate ecological diversity following species removal or extinction, and how the rediversified communities would compare to the original ones. Here we show that simple two-ecotype communities from the E. coli Long Term Evolution Experiment (LTEE) consistently rediversified into two ecotypes following the isolation of one of the ecotypes, coexisting via negative frequency-dependent selection. Communities separated by more than 30,000 generations of evolutionary time rediversify in similar ways. The rediversified ecotype appears to share a number of growth traits with the ecotype it replaces. However, the rediversified community is also different compared to the original community in ways relevant to the mechanism of ecotype coexistence, for example in stationary phase response and survival. We found substantial variation in the transcriptional states between the two original ecotypes, whereas the differences within the rediversified community were comparatively smaller, but with unique patterns of differential expression. Our results suggest that evolution may leave room for alternative diversification processes even in a maximally reduced community of only two strains. We hypothesize that the presence of alternative evolutionary pathways may be even more pronounced in communities of many species, highlighting an important role for perturbations, such as species removal, in evolving ecological communities.

evolutionary biology↗

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 dont 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 will be informative for parameterizing evolutionary models and studying potential mechanisms for increased drift. Author SummaryThe transmission of pathogens like SARS-CoV-2 is strongly affected by chance effects in the contact process between infected and susceptible individuals, collectively referred to as random genetic drift. We have an incomplete understanding of how genetic drift changes across time and locations. To address this gap, we developed a computational method that infers the strength of genetic drift from time series genomic data that corrects for non-biological noise and is computationally scalable to the large numbers of sequences available for SARS-CoV-2, overcoming a major challenge of existing methods. Using this method, we quantified the strength of genetic drift for SARS-CoV-2 transmission in England throughout time and across locations. These estimates constrain potential mechanisms and help parameterize models of SARS-CoV-2 evolution. More generally, the computational scalability of our method will become more important as increasingly large genomic datasets become more common.

evolutionary biology↗

Quantifying the Adaptive Potential of a Nascent Bacterial Community

The fitness effects of all possible mutations available to an organism largely shapes the dynamics of evolutionary adaptation. Tremendous progress has been made in quantifying the strength and abundance of selected mutations available to single microbial species in simple environments, lacking strong ecological interactions. However, the adaptive potential of strains that are part of multi-strain communities remains largely unclear. We sought to fill this gap by analyzing a stable community of two closely related ecotypes ("L" and "S") shortly after they emerged within the E. coli Long-Term Evolution Experiment (LTEE). We engineered genome-wide barcoded transposon libraries to measure the fitness effects of all possible gene knockouts in the coexisting strains as well as their ancestor, for many different, ecologically relevant conditions. We found that the fitness effects of many gene knockouts sensitively depends on the genetic background and the ecological conditions, as set by the abiotic environment and relative frequency of both ecotypes. Despite the idiosyncratic behavior of individual knockouts, we still see consistent statistical patterns of fitness effect variation across both genetic background and community composition. Genes that are in the same operon, or that strongly interact with each other, are more likely to be correlated with each other across backgrounds compared to random pairs of genes. Additionally, fitness effects are correlated with evolutionary outcomes for a number of conditions, possibly revealing shifting patterns of adaptation. Together, our results reveal how ecological and epistatic effects combine to drive adaptive potential in a nascent ecological community.

evolutionary biology↗