Biology subjects

Worthan, S. B.

Publications and source records attributed to Worthan, S. B..

5 recordsLinked to original sources

bioRxiv2026

Environment-dependent epistasis shapes adaptation to fluctuating resources.

Microbial populations frequently experience fluctuations in resource availability, yet how these fluctuations reshape genetic interactions during adaptation remains unclear. Here, we identify the rapid evolution of latent antimicrobial susceptibility in Escherichia coli populations experimentally evolved under repeated feast-famine cycles. Longitudinal population genomics revealed recurrent mutations in the transport genes acrB and ompF, and reconstruction of these mutations demonstrated environment-dependent fitness effects characterized by positive epistasis after 1 day of culture and reciprocal sign epistasis after 10 days. Together, our results support a two-step adaptive trajectory in which mutations affecting efflux are followed by changes in porin permeability, generating genotypes that are jointly beneficial across feast and famine. More broadly, our findings demonstrate how fluctuating environments reshape adaptive genetic interactions, producing historically contingent evolutionary trajectories and latent phenotypes. Article SummaryHow fluctuating environments shape genetic interactions and evolutionary trajectories remains a central question in evolutionary genetics. We identified latent antimicrobial susceptibility in Escherichia coli populations evolved under repeated feast-famine cycles and reconstructed evolved mutations to resolve the genotype-to-phenotype map underlying this trait. The responsible mutations arose in key transport genes, exhibited environmental-dependent epistasis, and increased fitness across both feast and famine conditions. Our findings provide experimental evidence that fluctuating environments can select for interacting mutations that optimize fitness across a dynamic adaptive seascape.

evolutionary biology↗

bioRxiv2025

Historical Contingency Limits Adaptive Diversification in a Spatially Structured Environment

Understanding how genotype-by-environment (GxE) interactions influence evolutionary trajectories and contribute to historical contingency is key to predicting evolution. In spatially structured, heterogeneous environments, populations often diversify into ecotypes, resulting in niche specialization. However, the ability to specialize depends not only on ecological opportunity but also on whether genetic variation permits access to novel niches, as genetic disruptions may inhibit adaptation unless alternative trajectories or compensatory mutations are subsequently accessible. Previously, we demonstrated that Escherichia coli populations rapidly diversify into two co-existing ecotypes in a nutrient-rich, spatially structured environment. The adaptation of both ecotypes results in benefits only perceived in the spatially structured culture tube environment. Here, diversification is initiated by first-step mutations associated with the overexpression of genes encoding the type 1 fimbria, the major attachment pilus involved in biofilm development, enabling range expansion and allowing E. coli to occupy the surface-air interface of the culture tube. To investigate how first-step mutations shape evolutionary trajectories, we experimentally evolved wild-type and fimbrial-deficient ({Delta}fimA) E. coli for 91 days in both structured (tube) and unstructured (flask) environments. While a fimA deletion initially confers a fitness benefit by avoiding the cost of insufficient biofilm formation, it ultimately prevents range expansion in structured environments and is not compensated by expression of cryptic fimbriae by the end of experimental evolution. As a result, {Delta}fimA populations show constrained adaptation in tubes compared to wild-type. Alternatively, both genotypes perform similarly in flasks, where biofilm formation is not advantageous and whole population sequencing reveals that flask-evolved populations similar early mutational trajectories. Our results highlight the ruggedness of the adaptive landscape in structured environments and show how an initially beneficial mutation can trap a lineage on a local fitness peak, underscoring the importance of GxE interactions and early mutational events in shaping the predictability and contingency of evolutionary outcomes.

evolutionary biology↗

bioRxiv2024

Evolution of pH-sensitive transcription termination during adaptation to repeated long-term starvation.

Fluctuating environments that consist of regular cycles of co-occurring stress are a common challenge faced by cellular populations. For a population to thrive in constantly changing conditions, an ability to coordinate a rapid cellular response is essential. Here, we identify a mutation conferring an arginine-to-histidine (Arg to His) substitution in the transcription terminator Rho. The rho R109H mutation frequently arose in E. coli populations experimentally evolved under repeated long-term starvation conditions, during which feast and famine result in drastic environmental pH fluctuations. Metagenomic sequencing revealed that populations containing the rho mutation also possess putative loss-of-function mutations in ydcI, which encodes a recently characterized transcription factor associated with pH homeostasis. Genetic reconstructions of these mutations show that the rho allele confers a plastic alkaline-induced reduction of Rho function that, when found in tandem with a {Delta}ydcI allele, leads to intracellular alkalinization and genetic assimilation of Rho mutant function. We further identify Arg to His substitutions at analogous sites in rho alleles from species originating from fluctuating alkaline environments. Our results suggest that Arg to His substitutions in global regulators of gene expression can serve to rapidly coordinate complex responses through pH sensing and shed light on how cellular populations across the tree of life use environmental cues to coordinate rapid responses to complex, fluctuating environments.

microbiology↗

bioRxiv2023

Trade-offs, trade-ups, and high mutational parallelism underlie microbial adaptation to extreme feast/famine

Microbes are robust organisms capable of rapidly adapting to complex stress, enabling the colonization of harsh environments. In nature, microbes are regularly challenged by starvation, which is a particularly complex stress because resource limitation often co-occurs with changes in pH, osmolarity, and toxin accumulation created by metabolic waste. Often overlooked are the additional complications introduced by eventual resource replenishment as successful microbes must withstand rapid environmental shifts before swiftly capitalizing on replenished resources to avoid invasion by competing species. To understand how microbes navigate trade-offs between growth and survival, ultimately adapting to thrive in environments with extreme fluctuations, we experimentally evolved 16 Escherichia coli populations for 900 days to repeated feast/famine cycles of 100-day starvation before resource replenishment. Using longitudinal population-genomic analysis, we found that evolution in response to extreme feast/famine is characterized by narrow adaptive trajectories with high mutational parallelism and notable mutational order. Genetic reconstructions reveal that early mutations result in trade-offs for biofilm and motility but trade-ups for growth and survival, as these mutations conferred correlated advantages during both short-term and long-term culture. Our results demonstrate how microbes can navigate the adaptive landscapes of regularly fluctuating conditions and ultimately follow mutational trajectories that confer benefits across diverse environments.

evolutionary biology↗

bioRxiv2021

A ribosomal protein variant that confers macrolide resistance differentially regulates acid resistance, catabolism, and biofilm formation related genes in Escherichia coli

Mutational changes in bacterial ribosomes that confer antibiotic resistance decrease cell fitness. Determining the genetic factors that interconnect antibiotic resistance and cell fitness is critical in the fight against bacterial infections. Here, we describe gene expression and phenotypic changes presented in Escherichia coli cells carrying an uL22(K90D) mutant ribosomal protein, which showed growth defects and resistance to macrolide antibiotics. Ribosome profiling analyses revealed reduced expression of operons involved in catabolism, electron transportation, indole production, and lysine-decarboxylase acid resistance. In general, ribosome occupancy was increased at rare codons while translation initiation of proximal genes in several of the affected operons was substantially reduced. Decline of the activity of these genes was accompanied by increased expression of macrolide multidrug efflux pumps, the glutamate-decarboxylase regulon, and the autoinducer-2 metabolic regulon. In concordance with these changes, uL22(K90D) mutant cells grew better in acidic conditions and generated more biofilm in static cultures than their parental strain. Our work provides new insights on how mutations in ribosomal proteins induce the acquisition of macrolide and pH resistance, and increase the ability to generate biofilms.

genomics↗