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1. Bioenergetics and the Evolution of Cellular Traits

   https://doi.org/10.1146/annurev-biophys-070524-090334  

   Schavemaker, Paul E; Lynch, Michael (May 2025, Annual Review of Biophysics)

   Evolutionary processes have transformed simple cellular life into a great diversity of forms, ranging from the ubiquitous eukaryotic cell design to the more specific cellular forms of spirochetes, cyanobacteria, ciliates, heliozoans, amoeba, and many others. The cellular traits that constitute these forms require an evolutionary explanation. Ultimately, the persistence of a cellular trait depends on its net contribution to fitness, a quantitative measure. Independent of any positive effects, a cellular trait exhibits a baseline energetic cost that needs to be accounted for when quantitatively examining its net fitness effect. Here, we explore how the energetic burden introduced by a cellular trait quantitatively affects cellular fitness, describe methods for determining cell energy budgets, summarize the costs of cellular traits across the tree of life, and examine how the fitness impacts of these energetic costs compare to other evolutionary forces and trait benefits. 

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2. Damage-Fitness Model: Evaluation and synthesis

   https://doi.org/10.1093/icb/icz060  

   Wada, Haruka; Heidinger, Britt (June 2019, Integrative and Comparative Biology)

   Abstract Decades of research into stress responses have highlighted large variation among individuals, populations, and species, and the sources of this variation have been a center of research across disciplines. The most common measure of the vertebrate stress response is glucocorticoids. However, the predictive power of glucocorticoid responses to fitness is surprisingly low. This is partly because the hormone levels rapidly change in response to stressor exposure and elevated levels at one time point can indicate either that glucocorticoids are helping the organism cope with the stressor or that dysregulation of hormone release is harming the organism. Meaning, the fitness consequences of the stressor depends on how efficient the stress responses are at negating the harmful impacts of stressors to cells and tissues. To encompass the idea of the efficiency of stress responses and to integrate cellular and organismal stress responses, a new theoretical model called the Damage-Fitness Model was developed. The model focuses on the downstream effects of stress responses and predicts that the accumulation of damage in cells and tissues (e.g., persistent damage to proteins, lipids, and DNA) negatively impacts fitness components. In this mini-review, we examine evidence supporting the Damage-Fitness Model and explore new directions forward. 

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3. Idiosyncratic Fitness Costs of Ampicillin-Resistant Mutants Derived from a Long-Term Experiment with Escherichia coli

   https://doi.org/10.3390/antibiotics11030347  

   Jordan, Jalin A.; Lenski, Richard E.; Card, Kyle J. (March 2022, Antibiotics)

   Antibiotic resistance is a growing concern that has prompted a renewed focus on drug discovery, stewardship, and evolutionary studies of the patterns and processes that underlie this phenomenon. A resistant strain’s competitive fitness relative to its sensitive counterparts in the absence of drug can impact its spread and persistence in both clinical and community settings. In a prior study, we examined the fitness of tetracycline-resistant clones that evolved from five different Escherichia coli genotypes, which had diverged during a long-term evolution experiment. In this study, we build on that work to examine whether ampicillin-resistant mutants are also less fit in the absence of the drug than their sensitive parents, and whether the cost of resistance is constant or variable among independently derived lines. Like the tetracycline-resistant lines, the ampicillin-resistant mutants were often less fit than their sensitive parents, with significant variation in the fitness costs among the mutants. This variation was not associated with the level of resistance conferred by the mutations, nor did it vary across the different parental backgrounds. In our earlier study, some of the variation in fitness costs associated with tetracycline resistance was explained by the effects of different mutations affecting the same cellular pathway and even the same gene. In contrast, the variance among the ampicillin-resistant mutants was associated with different sets of target genes. About half of the resistant clones suffered large fitness deficits, and their mutations impacted major outer-membrane proteins or subunits of RNA polymerases. The other mutants experienced little or no fitness costs and with, one exception, they had mutations affecting other genes and functions. Our findings underscore the importance of comparative studies on the evolution of antibiotic resistance, and they highlight the nuanced processes that shape these phenotypes. 

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4. A responsive living material prepared by diffusion reveals extracellular enzyme activity of cyanobacteria

   https://doi.org/10.1073/pnas.2424405122  

   Tang, Lisa; Soulier, Nathan T; Wheeler, Rebecca; Pokorski, Jonathan K; Golden, James W; Golden, Susan S; Bae, Jinhye (May 2025, Proceedings of the National Academy of Sciences)

   Stimuli-responsive engineered living materials (ELMs) can respond to environmental or biochemical cues and have broad utility in biological sensors and machines, but have traditionally been limited to biocompatible scaffolds. This is because they are typically made by mixing cells into a precursor solution before crosslinking. Here, we demonstrate a diffusion mechanism for incorporating cells of the cyanobacteriumSynechococcus elongatussp. PCC 7942 (S. elongatus) into nanoclay-poly-N-isopropylacrylamide (NC-PNIPAm), a hydrogel with a cytotoxic precursor, by exploiting its temperature-dependent shape-morphing behavior. Subsequent growth ofS. elongatuscaused a decrease in the bending curvature and stiffness (local Young’s modulus) of NC-PNIPAm due to partial degradation by an unannotated enzyme. Creation and observation of this cyanobacteria-hydrogel ELM showcases a method for diffusing cells into a hydrogel as well as characterizing an extracellular enzyme. 

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5. DR-BERT: A protein language model to annotate disordered regions

   https://doi.org/10.1016/j.str.2024.04.010  

   Nambiar, Ananthan; Forsyth, John Malcolm; Liu, Simon; Maslov, Sergei (August 2024, Structure)

   Despite their lack of a rigid structure, intrinsically disordered regions (IDRs) in proteins play important roles in cellular functions, including mediating protein-protein interactions. Therefore, it is important to computationally annotate IDRs with high accuracy. In this study, we present Disordered Region prediction using Bidirectional Encoder Representations from Transformers (DR-BERT), a compact protein language model. Unlike most popular tools, DR-BERT is pretrained on unannotated proteins and trained to predict IDRs without relying on explicit evolutionary or biophysical data. Despite this, DR-BERT demonstrates significant improvement over existing methods on the Critical Assessment of protein Intrinsic Disorder (CAID) evaluation dataset and outperforms competitors on two out of four test cases in the CAID 2 dataset, while maintaining competitiveness in the others. This performance is due to the information learned during pretraining and DR- BERT’s ability to use contextual information. 

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