@article{19965, abstract = {Multiagent learning is challenging when agents face mixed-motivation interactions, where conflicts of interest arise as agents independently try to optimize their respective outcomes. Recent advancements in evolutionary game theory have identified a class of “zero-determinant” strategies, which confer an agent with significant unilateral control over outcomes in repeated games. Building on these insights, we present a comprehensive generalization of zero-determinant strategies to stochastic games, encompassing dynamic environments. We propose an algorithm that allows an agent to discover strategies enforcing predetermined linear (or approximately linear) payoff relationships. Of particular interest is the relationship in which both payoffs are equal, which serves as a proxy for fairness in symmetric games. We demonstrate that an agent can discover strategies enforcing such relationships through experience alone, without coordinating with an opponent. In finding and using such a strategy, an agent (“enforcer”) can incentivize optimal and equitable outcomes, circumventing potential exploitation. In particular, from the opponent’s viewpoint, the enforcer transforms a mixed-motivation problem into a cooperative problem, paving the way for more collaboration and fairness in multiagent systems.}, author = {Mcavoy, Alex and Sehwag, Udari Madhushani and Hilbe, Christian and Chatterjee, Krishnendu and Barfuss, Wolfram and Su, Qi and Leonard, Naomi Ehrich and Plotkin, Joshua B.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {25}, publisher = {National Academy of Sciences}, title = {{Unilateral incentive alignment in two-agent stochastic games}}, doi = {10.1073/pnas.2319927121}, volume = {122}, year = {2025}, } @article{20289, abstract = {Cell and tissue movement in development, cancer invasion, and immune response relies on chemical or mechanical guidance cues. In many systems, this behavior is locally directed by self-generated signaling gradients rather than long-range, prepatterned cues. However, how heterogeneous mixtures of cells interact nonreciprocally and navigate through self-generated gradients remains largely unexplored. Here, we introduce a theoretical framework for the self-organized chemotaxis of heterogeneous cell populations. We find that the relative chemotactic sensitivities of different cell populations control their long-time coupling and comigration dynamics, with boundary conditions such as external cell and attractant reservoirs substantially influencing the migration patterns. Our model predicts an optimal parameter regime that enables robust and colocalized migration. We test our theoretical predictions with in vitro experiments demonstrating the comigration of distinct immune cell populations, and quantitatively reproduce observed migration patterns under wild-type and perturbed conditions. Interestingly, immune cell comigration occurs close to the predicted optimal regime. Finally, we incorporate mechanical interactions into our framework, revealing a nontrivial interplay between chemotactic and mechanical nonreciprocity in driving collective migration. Together, our findings suggest that self-generated chemotaxis is a robust strategy for the navigation of mixed cell populations.}, author = {Ucar, Mehmet C and Zane, Alsberga and Alanko, Jonna H and Sixt, Michael K and Hannezo, Edouard B}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {34}, publisher = {National Academy of Sciences}, title = {{Self-generated chemotaxis of mixed cell populations}}, doi = {10.1073/pnas.2504064122}, volume = {122}, year = {2025}, } @article{20492, abstract = {The glassy thermal conductivities observed in crystalline inorganic perovskites such as Cs3Bi2I6Cl3 are perplexing and lacking theoretical explanations. Here, we first experimentally measure its thermal transport behavior from 20 to 300 K, after synthesizing Cs3Bi2I6Cl3 single crystals. Using path-integral molecular dynamics simulations driven by machine learning potentials, we reveal that Cs3Bi2I6Cl3 has large lattice distortions at low temperatures, which may be related to the large atomic size mismatch. Employing the Wigner formulation of thermal transport, we reproduce theexperimental thermal conductivities based on lattice-distorted structures. This studythus provides a framework for predicting and understanding glassy thermal transportin materials with strong lattice disorder.}, author = {Zeng, Zezhu and Fan, Zheyong and Simoncelli, Michele and Chen, Chen and Liang, Ting and Chen, Yue and Thornton, Geoff and Cheng, Bingqing}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {41}, pages = {e2415664122}, publisher = {National Academy of Sciences}, title = {{Lattice distortion leads to glassy thermal transport in crystalline Cs3Bi2I6Cl3}}, doi = {10.1073/pnas.2415664122}, volume = {122}, year = {2025}, } @article{20530, abstract = {Cells must coordinate DNA segregation with cytokinesis to ensure that each daughter cell inherits a complete genome. Here, we explore how DNA segregation and division are mechanistically coupled in archaeal relatives of eukaryotes, which lack Cyclin-dependent kinase (CDK)/Cyclins. Using live cell imaging, we first describe the series of sequential changes in DNA organization that accompany cell division in Sulfolobus, which computational modeling shows likely aid genome segregation. Through a perturbation analysis we identify a regulatory checkpoint which ensures that the compaction of the genome into two spatially segregated nucleoids only occurs once cells have assembled a division ring—which also defines the axis of DNA segregation. Finally, we show that DNA compaction and segregation depend, in part, on a ParA homologue, SegA, and its partner SegB, whose absence leads to bridging DNA. Taken together, these data show how regulatory checkpoints like those operating in eukaryotes aid high-fidelity division in an archaeon.}, author = {Parham, Joe and Sorichetti, Valerio and Cezanne, Alice and Foo, Sherman and Kuo, Yin Wei and Hoogenberg, Baukje and Radoux-Mergault, Arthur and Mawdesley, Eloise and Gatward, Lydia Daniels and Boulanger, Jerome and Schulze, Ulrike and Šarić, Anđela and Baum, Buzz}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {42}, pages = {e2513939122}, publisher = {National Academy of Sciences}, title = {{Temporal and spatial coordination of DNA segregation and cell division in an archaeon}}, doi = {10.1073/pnas.2513939122}, volume = {122}, year = {2025}, } @article{20635, abstract = {Plants have evolved sophisticated mechanisms to adapt to environmental changes, with root gravitropism playing a pivotal role in nutrient and water acquisition. Our study reveals that SnRK2 kinases (SnRK2.2 and SnRK2.3) are critical regulators of root gravitropism through their direct phosphorylation of the auxin transporter PIN2 at S259. We demonstrate that SnRK2s-mediated phosphorylation modulates both the polar localization and transport activity of PIN2. Importantly, SnRK2s function antagonistically to the AGCVIII kinase PID, which phosphorylates PIN2 at a distinct site (S258), establishing a regulatory balance essential for adaptive root growth. Structural modeling and phosphorylation assays further suggest that SnRK2s-mediated phosphorylation at S259 sterically hinders access of PID to S258, providing a mechanistic basis for their antagonistic relationship. These findings uncover a novel regulatory mechanism, by which plants fine-tune root developmental programs to adapt to environmental stimuli, highlighting the evolutionary significance of multilayered kinase-mediated regulation in plant adaptation.}, author = {Sheng, F and Gao, Y and Wang, Y and Li, Y and Zhang, JA and Zhang, Z and Qin, X and Zhang, S and Song, W and Li, J and Guo, Y and Friml, Jiří and Gong, Z and Zhang, Q and Zhang, J}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {39}, pages = {e2512274122}, publisher = {National Academy of Sciences}, title = {{Antagonistic SnRK2 and PID kinases' action on auxin transport-mediated root gravitropism}}, doi = {10.1073/pnas.2512274122}, volume = {122}, year = {2025}, } @article{20663, abstract = {Gravitropism, the patterning of postembryonic growth in relation to the gravity vector, allows plants to optimize the use of limited and nonhomogenous resources in their immediate environment. Since the current model of root gravitropism has not been able to integrate all aspects of the response (perception, response, and behavior), research on gravitropism has been dominated by different theories attempting to conceptualize each aspect individually. In this work, we sought to reevaluate all the main components of the root graviresponse through the lens of angle dependence. We show angle dependence in Cholodny–Went-based auxin asymmetry and growth response, which we tracked back to angle-dependent variation in PIN asymmetry and statolith sedimentation in the columella. Thanks to this approach, we were able to suggest distinct roles for PINs and columella cell tiers, and a potential function for auxin vertical flux through the columella. Our findings provide a unifying framework to further explore the mechanisms that regulate angle-dependent gravitropic response, with major implications of time-dependent features of root graviresponse.}, author = {Roychoudhry, Suruchi and Sageman-Furnas, Katelyn and Taylor, Harry J. and Showpnil, Iftekhar and Wolverton, Chris and Friml, Jiří and Bianco, Marta Del and Kepinski, Stefan}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {46}, pages = {e2506400122}, publisher = {National Academy of Sciences}, title = {{Angle dependence as a unifying feature of root graviresponse modules}}, doi = {10.1073/pnas.2506400122}, volume = {122}, year = {2025}, } @article{20702, abstract = {Qualitative and quantitative orbital properties such as bonding/antibonding character, localization, and orbital energies are critical to how chemists understand reactivity, catalysis, and excited-state behavior. Despite this, representations of orbitals in deep learning models have been very underdeveloped relative to representations of molecular geometries and Hamiltonians. Here, we apply state-of-the-art equivariant deep learning architectures to the task of assigning global labels to orbitals, namely energies characterizations, given the molecular coefficients from Hartree–Fock or density functional theory. The architecture we have developed, the Cartesian Equivariant Orbital Network (CEONET), shows how molecular orbital coefficients are readily featurized as equivariant node features common to all graph-based machine-learned potentials. We find that CEONET performs well at predicting difficult quantitative labels such as the orbital energy and orbital entropy. Furthermore, we find that the CEONET representation provides an intuitive latent space for differentiating orbital character for the qualitative assignment of e.g. bonding or antibonding character. In addition to providing a useful representation for further integrating deep learning with electronic structure theory, we expect CEONET to be useful for automatizing and interpreting the results of advanced electronic structure methods such as complete active space self-consistent field theory. In particular, the ability of CEONET to infer multireference character via the orbital entropy paves the way toward the machine-learned selection of active spaces.}, author = {King, Daniel S. and Grzenda, Daniel and Zhu, Ray and Hudson, Nathaniel and Foster, Ian and Cheng, Bingqing and Gagliardi, Laura}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {48}, publisher = {National Academy of Sciences}, title = {{Cartesian equivariant representations for learning and understanding molecular orbitals}}, doi = {10.1073/pnas.2510235122}, volume = {122}, year = {2025}, } @article{20727, abstract = {Acoustic levitation provides a unique method for manipulating small particles as it completely evades effects from gravity, container walls, or physical handling. These advantages make it a tantalizing platform for studying complex phenomena in many-particle systems. In most standing-wave traps, however, particles interact via acoustic scattering forces that cause them to merge into a single dense object. Here, we introduce a complementary approach that combines acoustic levitation with electrostatic charging to assemble, adapt, and activate complex, separated many-particle systems. The key idea is to superimpose electrostatic repulsion on the intrinsic acoustic attraction, rendering a so-called “mermaid” potential where interactions are attractive at short range and repulsive at long range. By controlling the attraction–repulsion balance, we can levitate expanded structures where all particles are separated, collapsed structures where they are in contact, and hybrid ones consisting of both expanded and collapsed components. We find that collapsed and expanded structures are inherently stable, whereas hybrid ones exhibit transient stability governed by acoustically unstable dimers. Furthermore, we show how electrostatics allow us to adapt between configurations on the fly, either by quasistatic discharge or discrete up/down charge steps. Finally, we demonstrate how large structures experience selective energy pumping from the acoustic field—thrusting some particles into motion while others remain stationary—leading to complex dynamics including coupled rotations and oscillations. Our approach establishes a design space beyond acoustic collapse, offering possibilities to study many-particle systems with complex interactions, while suggesting pathways toward scalable integration into materials processing and other applications.}, author = {Shi, Sue and Hübl, Maximilian and Grosjean, Galien M and Goodrich, Carl Peter and Waitukaitis, Scott R}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {50}, pages = {e2516865122}, publisher = {National Academy of Sciences}, title = {{Electrostatics overcome acoustic collapse to assemble, adapt, and activate levitated matter}}, doi = {10.1073/pnas.2516865122}, volume = {122}, year = {2025}, } @article{20795, abstract = {The tropical climate variability is characterized by various oscillations across a range of timescales. Oscillations that imprint the tropical mean state are generally attributed to slow processes, such as the seasonal cycle or interannual variability. Here, we identify a pronounced tropics-wide intraseasonal oscillation (TWISO) in satellite observations and reanalyses. This oscillation, with a period of 30 to 60 d, is evident across multiple variables and involves interactions between convection, radiation, surface fluxes, and large-scale circulation. It is primarily manifested as convective perturbations in the tropical Indo-Pacific warm pool accompanied by oscillations in the large-scale tropical overturning circulation. Here, we examine the relationship between TWISO, the Madden–Julian Oscillation (MJO), and the instability of radiative-convective equilibrium. Certain phases of TWISO coincide with specific phases of the MJO, suggesting a potential connection between the two. However, although the MJO can amplify the oscillation amplitude of TWISO, it is not essential for TWISO to occur. Finally, due to its broad manifestation across the tropics, TWISO potentially exerts widespread influence on tropical weather and climate at regional scales.}, author = {Bao, Jiawei and Bony, Sandrine and Takasuka, Daisuke and Muller, Caroline J}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {48}, publisher = {National Academy of Sciences}, title = {{Tropics-wide intraseasonal oscillations}}, doi = {10.1073/pnas.2511549122}, volume = {122}, year = {2025}, } @article{18849, abstract = {Many biological systems operate near the physical limits to their performance, suggesting that aspects of their behavior and underlying mechanisms could be derived from optimization principles. However, such principles have often been applied only in simplified models. Here, we explore a detailed mechanistic model of the gap gene network in the Drosophila embryo, optimizing its 50+ parameters to maximize the information that gene expression levels provide about nuclear positions. This optimization is conducted under realistic constraints, such as limits on the number of available molecules. Remarkably, the optimal networks we derive closely match the architecture and spatial gene expression profiles observed in the real organism. Our framework quantifies the tradeoffs involved in maximizing functional performance and allows for the exploration of alternative network configurations, addressing the question of which features are necessary and which are contingent. Our results suggest that multiple solutions to the optimization problem might exist across closely related organisms, offering insights into the evolution of gene regulatory networks.}, author = {Sokolowski, Thomas R and Gregor, Thomas and Bialek, William and Tkačik, Gašper}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {1}, publisher = {National Academy of Sciences}, title = {{Deriving a genetic regulatory network from an optimization principle}}, doi = {10.1073/pnas.2402925121}, volume = {122}, year = {2025}, } @article{18850, abstract = {Biophysical constraints limit the specificity with which transcription factors (TFs) can target regulatory DNA. While individual nontarget binding events may be low affinity, the sheer number of such interactions could present a challenge for gene regulation by degrading its precision or possibly leading to an erroneous induction state. Chromatin can prevent nontarget binding by rendering DNA physically inaccessible to TFs, at the cost of energy-consuming remodeling orchestrated by pioneer factors (PFs). Under what conditions and by how much can chromatin reduce regulatory errors on a global scale? We use a theoretical approach to compare two scenarios for gene regulation: one that relies on TF binding to free DNA alone and one that uses a combination of TFs and chromatin-regulating PFs to achieve desired gene expression patterns. We find, first, that chromatin effectively silences groups of genes that should be simultaneously OFF, thereby allowing more accurate graded control of expression for the remaining ON genes. Second, chromatin buffers the deleterious consequences of nontarget binding as the number of OFF genes grows, permitting a substantial expansion in regulatory complexity. Third, chromatin-based regulation productively co-opts nontarget TF binding for ON genes in order to establish a “leaky” baseline expression level, which targeted activator or repressor binding subsequently up- or down-modulates. Thus, on a global scale, using chromatin simultaneously alleviates pressure for high specificity of regulatory interactions and enables an increase in genome size with minimal impact on global expression error.}, author = {Perkins, Mindy Liu and Crocker, Justin and Tkačik, Gašper}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {1}, publisher = {National Academy of Sciences}, title = {{Chromatin enables precise and scalable gene regulation with factors of limited specificity}}, doi = {10.1073/pnas.2411887121}, volume = {122}, year = {2025}, } @article{19036, abstract = {Neuronal processing of external sensory input is shaped by internally generated top–down information. In the neocortex, top–down projections primarily target layer 1, which contains NDNF (neuron-derived neurotrophic factor)-expressing interneurons and the dendrites of pyramidal cells. Here, we investigate the hypothesis that NDNF interneurons shape cortical computations in an unconventional, layer-specific way, by exerting presynaptic inhibition on synapses in layer 1 while leaving synapses in deeper layers unaffected. We first confirm experimentally that in the auditory cortex, synapses from somatostatin-expressing (SOM) onto NDNF neurons are indeed modulated by ambient Gamma-aminobutyric acid (GABA). Shifting to a computational model, we then show that this mechanism introduces a distinct mutual inhibition motif between NDNF interneurons and the synaptic outputs of SOM interneurons. This motif can control inhibition in a layer-specific way and introduces competition between NDNF and SOM interneurons for dendritic inhibition onto pyramidal cells on different timescales. NDNF interneurons can thereby control cortical information flow by redistributing dendritic inhibition from fast to slow timescales and by gating different sources of dendritic inhibition.}, author = {Naumann, Laura B and Hertäg, Loreen and Müller, Jennifer and Letzkus, Johannes J. and Sprekeler, Henning}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {4}, publisher = {National Academy of Sciences}, title = {{Layer-specific control of inhibition by NDNF interneurons}}, doi = {10.1073/pnas.2408966122}, volume = {122}, year = {2025}, } @article{19453, abstract = {A key feature of biological and artificial neural networks is the progressive refinement of their neural representations with experience. In neuroscience, this fact has inspired several recent studies in sensory and motor systems. However, less is known about how higher associational cortical areas, such as the hippocampus, modify representations throughout the learning of complex tasks. Here, we focus on associative learning, a process that requires forming a connection between the representations of different variables for appropriate behavioral response. We trained rats in a space-context associative task and monitored hippocampal neural activity throughout the entire learning period, over several days. This allowed us to assess changes in the representations of context, movement direction, and position, as well as their relationship to behavior. We identified a hierarchical representational structure in the encoding of these three task variables that was preserved throughout learning. Nevertheless, we also observed changes at the lower levels of the hierarchy where context was encoded. These changes were local in neural activity space and restricted to physical positions where context identification was necessary for correct decision-making, supporting better context decoding and contextual code compression. Our results demonstrate that the hippocampal code not only accommodates hierarchical relationships between different variables but also enables efficient learning through minimal changes in neural activity space. Beyond the hippocampus, our work reveals a representation learning mechanism that might be implemented in other biological and artificial networks performing similar tasks.}, author = {Chiossi, Heloisa and Nardin, Michele and Tkačik, Gašper and Csicsvari, Jozsef L}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {11}, publisher = {National Academy of Sciences}, title = {{Learning reshapes the hippocampal representation hierarchy}}, doi = {10.1073/pnas.2417025122}, volume = {122}, year = {2025}, } @article{19499, abstract = {Quantum hardware is inherently fragile and noisy. We find that the accuracy of traditional quantum error correction algorithms can be improved depending on the hardware. Given different hardware specifications, we automatically synthesize hardware-optimal algorithms for parity correction, qubit resetting, and GHZ (Greenberger–Horne–Zeilinger) state preparation. Using stochastic techniques from computer science, our method presents a computational tool to compute exact accuracy guarantees and synthesize optimal algorithms that are often different from traditional ones. We also show that improvements can be gained with respect to the Qiskit transpiler as we compute the hardware-optimal qubit mapping for the GHZ state-preparation problem.}, author = {Muroya Lei, Stefanie and Chatterjee, Krishnendu and Henzinger, Thomas A}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {12}, publisher = {National Academy of Sciences}, title = {{Hardware-optimal quantum algorithms}}, doi = {10.1073/pnas.2419273122}, volume = {122}, year = {2025}, } @article{19627, abstract = {Differentially private gradient descent (DP-GD) is a popular algorithm to train deep learning models with provable guarantees on the privacy of the training data. In the last decade, the problem of understanding its performance cost with respect to standard GD has received remarkable attention from the research community, which formally derived upper bounds on the excess population risk RP in different learning settings. However, existing bounds typically degrade with over-parameterization, i.e., as the number of parameters p gets larger than the number of training samples n -- a regime which is ubiquitous in current deep-learning practice. As a result, the lack of theoretical insights leaves practitioners without clear guidance, leading some to reduce the effective number of trainable parameters to improve performance, while others use larger models to achieve better results through scale. In this work, we show that in the popular random features model with quadratic loss, for any sufficiently large p , privacy can be obtained for free, i.e., |RP|=o(1) , not only when the privacy parameter ε has constant order, but also in the strongly private setting ε=o(1) . This challenges the common wisdom that over-parameterization inherently hinders performance in private learning.}, author = {Bombari, Simone and Mondelli, Marco}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {15}, publisher = {National Academy of Sciences}, title = {{Privacy for free in the overparameterized regime}}, doi = {10.1073/pnas.2423072122}, volume = {122}, year = {2025}, } @article{19728, abstract = {Root system integrates multiple environmental cues, chiefly gravity and soil humidity, to anchor plants in soil and forage for water. While the mechanism of auxin-mediated root gravitropism is comparably well-understood, the root’s capability to grow toward moist soil for water uptake and drought avoidance, termed root hydrotropism, remains largely mysterious. Here, we provide key insights into the mechanism of hydrotropic growth and assign a role to the master regulator of hydrotropism, MIZU-KUSSEI 1 (MIZ1). We show that efficient hydrotropism requires the attenuation of antagonistically acting gravitropism, which is inhibited under drought conditions. Drought stress interferes with subcellular trafficking and the lateral mobility of PIN auxin transporters, which are polarly localized at the root cell plasma membranes. This leads to defects in PIN2 polarity and gravity-induced polarization of PIN3, ultimately inhibiting gravity-induced auxin redistribution and root bending. The miz1 mutant is defective in all these regulations, and in support of MIZ1’s action on PINs, pin mutations rescue the hydrotropic defects in the miz1 mutant. These observations identify a mechanism for how drought via MIZ1 attenuates gravitropism to promote root hydrotropism for efficient water foraging under drought conditions.}, author = {Zhang, Yuzhou and Bao, Zhulatai and Smoljan, Adrijana and Liu, Yifan and Wang, Huihui and Friml, Jiří}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {20}, publisher = {National Academy of Sciences}, title = {{Foraging for water by MIZ1-mediated antagonism between root gravitropism and hydrotropism}}, doi = {10.1073/pnas.2427315122}, volume = {122}, year = {2025}, } @article{20857, abstract = {Evolutionary games provide a flexible mathematical framework for many problems in biology and social evolution. Prisoners’ dilemma, and in particular, the important special case of donation games, represents social dilemmas where cooperation is mutually beneficial, yet defection is preferred by selfish agents. In evolutionary games on networks, the agents interact over a population structure. The existence of population structures that promote cooperative behavior is a fascinating and active research topic. Previous research establishes structures promoting cooperation in the limit of weak selection where the benefit-to-cost ratio β exceeds 1.5. The existence of such structures for medium and strong selection for 1 < ß < 2 and for weak selection for 1 < ß < 1.5 has been a long-standing open question. First, we answer the open questions in the affirmative: For every selection strength and every ß > 1, we construct networks promoting cooperation. Second, we present a robustness result with respect to β and selection strength: Our structures promote cooperation for a range of these parameter values rather than specific parameter values. Finally, we supplement our theoretical results with simulation results on small population structures that show the effectiveness of our construction over well-studied population structures.}, author = {Svoboda, Jakub and Chatterjee, Krishnendu}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {51}, pages = {e2524109122}, publisher = {National Academy of Sciences}, title = {{Promoters of cooperation in evolutionary games}}, doi = {10.1073/pnas.2524109122}, volume = {122}, year = {2025}, } @article{19626, abstract = {Active regulation of gene expression, orchestrated by complex interactions of activators and repressors at promoters, controls the fate of organisms. In contrast, basal expression at uninduced promoters is considered to be a dynamically inert mode of nonfunctional “promoter leakiness,” merely a byproduct of transcriptional regulation. Here, we investigate the basal expression mode of the mar operon, the main regulator of intrinsic multiple antibiotic resistance in Escherichia coli, and link its dynamic properties to the noncanonical, yet highly conserved start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements across tens of generations reveal that basal expression consists of rare stochastic gene expression pulses, which maximize variability in wildtype and, surprisingly, transiently accelerate cellular elongation rates. Competition experiments show that basal expression confers fitness advantages to wildtype across several transitions between exponential and stationary growth by shortening lag times. The dynamically rich basal expression of the mar operon has likely been evolutionarily maintained for its role in growth homeostasis of Enterobacteria within the gut environment, thereby allowing other ancillary gene regulatory roles to evolve, e.g., control of costly-to-induce multidrug efflux pumps. Understanding the complex selection forces governing genetic systems involved in intrinsic multidrug resistance is crucial for effective public health measures.}, author = {Jain, Kirti and Hauschild, Robert and Bochkareva, Olga and Römhild, Roderich and Tkačik, Gašper and Guet, Calin C}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {15}, publisher = {National Academy of Sciences}, title = {{Pulsatile basal gene expression as a fitness determinant in bacteria}}, doi = {10.1073/pnas.2413709122}, volume = {122}, year = {2025}, } @article{14478, abstract = {Entire chromosomes are typically only transmitted vertically from one generation to the next. The horizontal transfer of such chromosomes has long been considered improbable, yet gained recent support in several pathogenic fungi where it may affect the fitness or host specificity. To date, it is unknown how these transfers occur, how common they are and whether they can occur between different species. In this study, we show multiple independent instances of horizontal transfers of the same accessory chromosome between two distinct strains of the asexual entomopathogenic fungusMetarhizium robertsiiduring experimental co-infection of its insect host, the Argentine ant. Notably, only the one chromosome – but no other – was transferred from the donor to the recipient strain. The recipient strain, now harboring the accessory chromosome, exhibited a competitive advantage under certain host conditions. By phylogenetic analysis we further demonstrate that the same accessory chromosome was horizontally transferred in a natural environment betweenM. robertsiiand another congeneric insect pathogen,M. guizhouense. Hence horizontal chromosome transfer is not limited to the observed frequent events within species during experimental infections but also occurs naturally across species. The transferred accessory chromosome contains genes that might be involved in its preferential horizontal transfer, encoding putative histones and histone-modifying enzymes, but also putative virulence factors that may support its establishment. Our study reveals that both intra- and interspecies horizontal transfer of entire chromosomes is more frequent than previously assumed, likely representing a not uncommon mechanism for gene exchange.Significance StatementThe enormous success of bacterial pathogens has been attributed to their ability to exchange genetic material between one another. Similarly, in eukaryotes, horizontal transfer of genetic material allowed the spread of virulence factors across species. The horizontal transfer of whole chromosomes could be an important pathway for such exchange of genetic material, but little is known about the origin of transferable chromosomes and how frequently they are exchanged. Here, we show that the transfer of accessory chromosomes - chromosomes that are non-essential but may provide fitness benefits - is common during fungal co-infections and is even possible between distant pathogenic species, highlighting the importance of horizontal gene transfer via chromosome transfer also for the evolution and function of eukaryotic pathogens.}, author = {Habig, Michael and Grasse, Anna V and Müller, Judith and Stukenbrock, Eva H. and Leitner, Hanna and Cremer, Sylvia}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {11}, publisher = {National Academy of Sciences}, title = {{Frequent horizontal chromosome transfer between asexual fungal insect pathogens}}, doi = {10.1073/pnas.2316284121}, volume = {121}, year = {2024}, } @article{18108, abstract = {Here we announce the construction and properties of a big commutative subalgebra of the Kirillov algebra attached to a finite dimensional irreducible representation of a complex semisimple Lie group. They are commutative finite flat algebras over the cohomology of the classifying space of the group. They are isomorphic with the equivariant intersection cohomology of affine Schubert varieties, endowing the latter with a new ring structure. Study of the finer aspects of the structure of the big algebras will also furnish the stalks of the intersection cohomology with ring structure, thus ringifying Lusztig’s q-weight multiplicity polynomials i.e., certain affine Kazhdan–Lusztig polynomials.}, author = {Hausel, Tamás}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {38}, publisher = {National Academy of Sciences}, title = {{Commutative avatars of representations of semisimple Lie groups}}, doi = {10.1073/pnas.2319341121}, volume = {121}, year = {2024}, }