Proceedings of the National Academy of Sciences of the United States of America最新文献

{"title":"Where do fish go and why? For many species, nobody knows.","authors":"Amy McDermott","doi":"10.1073/pnas.2510827122","DOIUrl":"https://doi.org/10.1073/pnas.2510827122","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"31 1","pages":"e2510827122"},"PeriodicalIF":11.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144114143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation dynamics of ubiquitin-specific protease 7","authors":"Gabrielle J. Valles, Emilie J. Korchak, Dane H. Geddes-Buehre, Nancy Jaiswal, Dmitry M. Korzhnev, Irina Bezsonova","doi":"10.1073/pnas.2426632122","DOIUrl":"https://doi.org/10.1073/pnas.2426632122","url":null,"abstract":"Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that plays a crucial role in cellular processes, including the maintenance of genome stability and regulation of antiviral and immune responses. Its dysfunction is linked to various cancers and neurodevelopmental disorders such as Hao-Fountain syndrome. Unlike other USP-family enzymes, the triad of catalytic residues in USP7 adopts an inactive conformation and undergoes rearrangement into the active state upon substrate binding. Despite its potential importance for regulating the enzyme’s activity, the dynamics of USP7 have not been explored. In this study, we combine advanced CPMG NMR relaxation dispersion measurements with the analysis of enzyme kinetics to investigate the conformational dynamics of USP7 in solution and its role in enzyme activation. Our results suggest that apo-USP7 exists in a dynamic equilibrium, transiently switching between inactive and low-populated active conformations, indicating that enzyme activation can occur spontaneously, even in the absence of a substrate. Furthermore, we show that the Hao-Fountain syndrome-associated variant G392D enhances the conformational dynamics of the enzyme, leading to a significant increase in its catalytic activity. This study captures the sparsely populated, \"invisible\" active conformation of USP7 and demonstrates how changes in enzyme dynamics can contribute to activity, offering broader insights into enzyme function and disease mechanisms.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"135 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trait-space patterning is dictated by the tempo and mode of mutation","authors":"Stephen Martis, David J. Schwab, Trevor GrandPre","doi":"10.1073/pnas.2425607122","DOIUrl":"https://doi.org/10.1073/pnas.2425607122","url":null,"abstract":"In large, natural ecosystems, many ( <jats:italic toggle=\"yes\">≳</jats:italic> 1) phenotypically relevant mutants can emerge over the characteristic turnover time of the population. When this is the case, there can be ‘eco-evolutionary feedback’ between the dynamical processes that underlie mutation, selection and ecology. We show that, owing to such feedback, the precise details of the mutational process can have a qualitative impact on the long-term behavior of an eco-evolutionary system, in contrast to the classical population genetic assumption that all mutations can be modeled with an effective, homogeneous rate. We demonstrate this in the context of a version of MacArthur’s consumer-resource model in which consumers mutate along a resource preference trait-space. Starting from a stochastic individual-based model, we simulate the system in the case where mutations are exogenously generated at a fixed rate (e.g. via external mutagens) and in the case where mutations are coupled to replication (e.g. via DNA copying errors). We find that, surprisingly, replication-coupled mutations are capable of generating a patterned phase in the limit of fast ecological relaxation – precisely the regime where classical population genetic models are expected to operate. We derive a mean-field description of the stochastic model and show that the patterned phase comes about due to a Turing-like mechanism driven by the non-reciprocal and nonlinear nature of replicative mutations. Furthermore, we show that additional interactions like those due to host defense mechanisms can extend the patterned regime to arbitrarily high dimensional phenotype spaces. We demonstrate that these results are robust to demographic noise and model choices and we discuss systems in which this phenomenology might be relevant.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"16 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nonenzymatic RNA copying with a potentially primordial genetic alphabet","authors":"Ziyuan Fang, Xiwen Jia, Yanfeng Xing, Jack W. Szostak","doi":"10.1073/pnas.2505720122","DOIUrl":"https://doi.org/10.1073/pnas.2505720122","url":null,"abstract":"Nonenzymatic RNA copying is thought to have been responsible for the replication of genetic information during the origin of life. However, chemical copying with the canonical nucleotides (A, U, G, and C) strongly favors the incorporation of G and C and disfavors the incorporation of A and especially U because of the stronger G:C vs. A:U base pair and the weaker stacking interactions of U. Recent advances in prebiotic chemistry suggest that the 2-thiopyrimidines were precursors to the canonical pyrimidines, raising the possibility that they may have played an important early role in RNA copying chemistry. Furthermore, 2-thiouridine (s <jats:sup>2</jats:sup> U) and inosine (I) form by deamination of 2-thiocytidine (s <jats:sup>2</jats:sup> C) and A, respectively. We used thermodynamic and crystallographic analyses to compare the I:s <jats:sup>2</jats:sup> C and A:s <jats:sup>2</jats:sup> U base pairs. We find that the I:s <jats:sup>2</jats:sup> C base pair is isomorphic and isoenergetic with the A:s <jats:sup>2</jats:sup> U base pair. The I:s <jats:sup>2</jats:sup> C base pair is weaker than a canonical G:C base pair, while the A:s <jats:sup>2</jats:sup> U base pair is stronger than the canonical A:U base pair, so that a genetic alphabet consisting of s <jats:sup>2</jats:sup> U, s <jats:sup>2</jats:sup> C, I, and A generates RNA duplexes with uniform base pairing energies. Consistent with these results, kinetic analysis of nonenzymatic template-directed primer extension reactions reveals that s <jats:sup>2</jats:sup> C and s <jats:sup>2</jats:sup> U substrates bind similarly to I and A in the template, and vice versa. Our work supports the plausibility of a potentially primordial genetic alphabet consisting of s <jats:sup>2</jats:sup> U, s <jats:sup>2</jats:sup> C, I, and A and offers a potential solution to the long-standing problem of biased nucleotide incorporation during nonenzymatic template copying.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"135 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering spin coherence in core-shell diamond nanocrystals","authors":"Uri Zvi, Denis R. Candido, Adam M. Weiss, Aidan R. Jones, Lingjie Chen, Iryna Golovina, Xiaofei Yu, Stella Wang, Dmitri V. Talapin, Michael E. Flatté, Aaron P. Esser-Kahn, Peter C. Maurer","doi":"10.1073/pnas.2422542122","DOIUrl":"https://doi.org/10.1073/pnas.2422542122","url":null,"abstract":"Fluorescent diamond nanocrystals can host spin qubit sensors capable of probing the physical properties of biological systems with nanoscale spatial resolution. Sub-100 nm diamond nanosensors can readily be delivered into intact cells and even living organisms. However, applications beyond current proof-of-principle experiments require a substantial increase in sensitivity, which is limited by surface induced charge instability and electron-spin dephasing. In this work, we utilize engineered core-shell structures to achieve a drastic increase in qubit coherence times ( <jats:italic toggle=\"yes\">T</jats:italic> <jats:sub>2</jats:sub> ) from 1.1 to 35 μs in bare nanodiamonds to upward of 52 to 87 μs. We use electron-paramagnetic-resonance results to present a band bending model and connect silica encapsulation to the removal of deleterious mid-gap surface states that are negatively affecting the qubit’s spin properties. Combined with a 1.9-fold increase in particle luminescence these advances correspond to up to two-order-of-magnitude reduction in integration time. Probing qubit dynamics at a single particle level further reveals that the noise characteristics fundamentally change from a bath with spins that rearrange their spatial configuration during the course of an experiment to a more dilute static bath. The observed results shed light on the underlying mechanisms governing fluorescence and spin properties in diamond nanocrystals and offer an effective noise mitigation strategy based on engineered core-shell structures.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"35 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcineurin controls the cytokinesis machinery during thermal stress in Cryptococcus deneoformans","authors":"Vikas Yadav, Anna Floyd Averette, Rajendra Upadhya, Joseph Heitman","doi":"10.1073/pnas.2503751122","DOIUrl":"https://doi.org/10.1073/pnas.2503751122","url":null,"abstract":"Calcineurin is a highly conserved phosphatase that plays a central role in sensing calcium and governing transcriptional, posttranscriptional, and posttranslational signaling networks. Calcineurin is a heterodimer consisting of a catalytic A subunit and a regulatory B subunit. Through downstream effectors, calcineurin signaling drives myriad responses in different organisms. In the fungal pathogenic <jats:italic toggle=\"yes\">Cryptococcus</jats:italic> species complex that infects humans, calcineurin governs thermotolerance and is essential for growth at high temperature and pathogenesis. In <jats:italic toggle=\"yes\">Cryptococcus deneoformans</jats:italic> , the underlying molecular functions of this critical signaling cascade are not well understood. In this study, we conducted a genetic screen and identified genetic changes that suppress the requirement for calcineurin during high-temperature growth. Our results identified two mechanisms that bypass the requirement for calcineurin function. The first mechanism involves segmental aneuploidy via both amplification as well as loss of chromosome fragments. The second mechanism involves dominant amino acid substitution mutations in the genes encoding three proteins, Chs6, Imp2, and Cts1, orthologs of components of the Ingression Progression Complex required for septation and budding in <jats:italic toggle=\"yes\">Saccharomyces cerevisiae</jats:italic> . Loss of calcineurin activity causes chitin and chitosan accumulation and severe budding defects, whereas suppressor mutations largely restore growth and cytokinesis in the absence of calcineurin. These findings reveal that the calcineurin signaling cascade controls a conserved cytokinesis machinery at the mitotic exit network during thermal stress.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"11 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibiting 15-PGDH blocks blood–brain barrier deterioration and protects mice from Alzheimer’s disease and traumatic brain injury","authors":"Yeojung Koh, Edwin Vázquez-Rosa, Farrah Gao, Hongyun Li, Suwarna Chakraborty, Sunil Jamuna Tripathi, Sarah Barker, Zea Bud, Anusha Bangalore, Uapingena P. Kandjoze, Rose A León-Alvarado, Preethy S. Sridharan, Brittany A. Cordova, Youngmin Yu, Jiwon Hyung, Hua Fang, Salendra Singh, Ramachandra Katabathula, Thomas LaFramboise, Lakshmi Kasturi, James Lutterbaugh, Lydia Beard, Erika Cordova, Coral J. Cintrón-Pérez, Kathryn Franke, Mariana Franco Fragoso, Emiko Miller, Vidya Indrakumar, Kamryn L. Noel, Matasha Dhar, Kaouther Ajroud, Carlos Zamudio, Filipa Blasco Tavares Pereira Lopes, Evangeline Bambakidis, Xiongwei Zhu, Brigid Wilson, Margaret E. Flanagan, Tamar Gefen, Hisashi Fujioka, Stephen P. Fink, Amar B. Desai, Dawn Dawson, Noelle S. Williams, Young-Kwang Kim, Joseph M. Ready, Bindu D. Paul, Min-Kyoo Shin, Sanford D. Markowitz, Andrew A. Pieper","doi":"10.1073/pnas.2417224122","DOIUrl":"https://doi.org/10.1073/pnas.2417224122","url":null,"abstract":"Alzheimer’s disease (AD) and traumatic brain injury (TBI) are currently untreatable neurodegenerative disorders afflicting millions of people worldwide. These conditions are pathologically related, and TBI is one of the greatest risk factors for AD. Although blood–brain barrier (BBB) disruption drives progression of both AD and TBI, strategies to preserve BBB integrity have been hindered by lack of actionable targets. Here, we identify 15-hydroxyprostaglandin dehydrogenase (15-PGDH), an enzyme that catabolizes eicosanoids and other anti-inflammatory mediators, as a therapeutic candidate that protects the BBB. We demonstrate that 15-PGDH is enriched in BBB-associated myeloid cells and becomes markedly elevated in human and mouse models of AD and TBI, as well as aging, another major risk factor for AD. Pathological increase in 15-PGDH correlates with pronounced oxidative stress, neuroinflammation, and neurodegeneration, alongside profound BBB structural degeneration characterized by astrocytic endfeet swelling and functional impairment. Pharmacologic inhibition or genetic reduction of 15-PGDH in AD and TBI models strikingly mitigates oxidative damage, suppresses neuroinflammation, and restores BBB integrity. Most notably, inhibiting 15-PGDH not only halts neurodegeneration but also preserves cognitive function at levels indistinguishable from healthy controls. Remarkably, these neuroprotective effects in AD are achieved without affecting amyloid pathology, underscoring a noncanonical mechanism for treating AD. In a murine microglia cell line exposed to amyloid beta oligomer, major protection was demonstrated by multiple anti-inflammatory substrates that 15-PGDH degrades. Thus, our findings position 15-PGDH inhibition as a broad-spectrum strategy to protect the BBB and thereby preserve brain health and cognition in AD and TBI.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"61 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of photoreceptor protection upon targeting the Nrl–Nr2e3 pathway","authors":"Daniel P. Murphy, Alexander V. Kolesnikov, Cynthia L. Montana, Zaid M. Khaja, Yu Liu, Vladimir J. Kefalov, Joseph C. Corbo","doi":"10.1073/pnas.2500446122","DOIUrl":"https://doi.org/10.1073/pnas.2500446122","url":null,"abstract":"Acute knockout of the rod photoreceptor transcription factor <jats:italic toggle=\"yes\">Nrl</jats:italic> delays retinal degeneration in multiple mouse models of blindness, but the downstream transcriptomic changes that mediate these therapeutic effects are unknown. Here, we show that acute <jats:italic toggle=\"yes\">Nrl</jats:italic> knockout causes upregulation of a subset of cone genes in rods as well as downregulation of rod genes, including the rod-specific transcriptional repressor <jats:italic toggle=\"yes\">Nr2e3</jats:italic> . We hypothesized that <jats:italic toggle=\"yes\">Nr2e3</jats:italic> downregulation might mediate some of the therapeutic effects of <jats:italic toggle=\"yes\">Nrl</jats:italic> knockout. Indeed, acute knockout of <jats:italic toggle=\"yes\">Nr2e3</jats:italic> prevents photoreceptor degeneration and preserves visual function in mice with mutations in the catalytic subunit of the rod-specific phosphodiesterase ( <jats:italic toggle=\"yes\"> Pde6b <jats:sup>rd10/rd10</jats:sup> </jats:italic> ). Upregulation of <jats:italic toggle=\"yes\">Pde6c</jats:italic> , the cone-specific paralog of <jats:italic toggle=\"yes\">Pde6b</jats:italic> , in <jats:italic toggle=\"yes\">Nr2e3</jats:italic> -knockout rods is required to prevent degeneration in <jats:italic toggle=\"yes\"> Pde6b <jats:sup>rd10/rd10</jats:sup> </jats:italic> mice, suggesting that this therapeutic effect is mediated, at least in part, by a gene-replacement mechanism. In contrast, acute <jats:italic toggle=\"yes\">Nr2e3</jats:italic> knockout fails to prevent degeneration caused by loss- or gain-of-function mutations in Rhodopsin ( <jats:italic toggle=\"yes\"> Rho <jats:sup>−/−</jats:sup> </jats:italic> and <jats:italic toggle=\"yes\"> Rho <jats:sup>P23H/P23H</jats:sup> </jats:italic> ), whereas acute <jats:italic toggle=\"yes\">Nrl</jats:italic> knockout delays degeneration in both models. Surprisingly, the therapeutic effect of acute <jats:italic toggle=\"yes\">Nrl</jats:italic> knockout in <jats:italic toggle=\"yes\"> Pde6b <jats:sup>rd10/rd10</jats:sup> </jats:italic> mice does not depend on <jats:italic toggle=\"yes\">Pde6c</jats:italic> upregulation. These results suggest that acute <jats:italic toggle=\"yes\">Nrl</jats:italic> knockout may exert its therapeutic effects via a mechanism independent of <jats:italic toggle=\"yes\">Nr2e3</jats:italic> downregulation, perhaps by downregulating other rod genes. We conclude that acute <jats:italic toggle=\"yes\">NRL</jats:italic> knockout may be a promising gene-independent strategy for preventing photoreceptor degeneration in human patients.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"136 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD83 suppresses endogenous March-I-dependent MHC class II ubiquitination, endocytosis, and degradation","authors":"Sunil Kaul, Nelson B. Cole, Joanna Bandola-Simon, Ying Lu, Elena Tondini, Even Walseng, Paul A. Roche","doi":"10.1073/pnas.2504077122","DOIUrl":"https://doi.org/10.1073/pnas.2504077122","url":null,"abstract":"MHC class II glycoproteins (MHC-II) bind peptides derived from exogenous antigens and dendritic cells (DCs) present these peptide MHC-II (pMHC-II) complexes to antigen-specific CD4 T cells during immune responses. The turnover of surface pMHC-II on antigen-presenting cells (APCs) is controlled by ubiquitin-mediated degradation of pMHC-II by the E3 ubiquitin ligase March-I. To study March-I protein expression, we have generated a mouse in which a V5 epitope-tag was knocked-in to the endogenous March-I gene, thereby allowing us to follow the fate of March-I using high-affinity anti-V5 antibodies. Quantitative analysis revealed that resting spleen DCs and B cells express only ~500 and 125 March-I molecules/cell, respectively. Endogenous March-I protein has a very short half-life in DCs and March-I mRNA, March-I protein, and MHC-II ubiquitination are rapidly terminated upon activation of both DCs and B cells. Like March-I, CD83 is a known regulator of MHC-II expression in APCs and we also show that CD83 suppresses endogenous March-I-dependent MHC-II ubiquitination, endocytosis, and degradation in mouse spleen DCs. Thus, our study reveals molecular mechanisms for both March-I- and CD83-dependent regulation of MHC-II expression in APCs.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"45 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Partner dependency alters patterns of coevolutionary selection in mutualisms","authors":"Mayra C. Vidal, Cong Liu, Shengpei Wang, Kari A. Segraves","doi":"10.1073/pnas.2424983122","DOIUrl":"https://doi.org/10.1073/pnas.2424983122","url":null,"abstract":"Coevolution is a ubiquitous driver of diversification in both mutualistic and antagonistic interactions between species. In mutualisms, coevolution can result in trait complementarity between partners that facilitates their persistence. Despite its importance, most of what we know about coevolution in mutualism comes from obligate interactions, whereas we know comparatively little about facultative interactions, arguably the most common type of mutualism. To evaluate coevolutionary dynamics in facultative mutualism and test how it compares with obligate mutualisms, we used a synthetic yeast mutualism where the partners exchange essential nutrient resources. We manipulated mutualism dependency by controlling the availability of mutualistic resources in the environment and measured coevolution via time-shift assays and tracking the evolution of mutualistic traits over time. In addition, we genotyped the evolved and ancestral mutualists to test for differences in the strength of coevolutionary selection between facultative and obligate mutualisms. We found evidence of coevolution in both facultative and obligate mutualisms, but coevolution was weaker and slower in facultative mutualisms. We also found evidence for evolution of trait complementarity in obligate mutualisms but not in facultative mutualisms. Furthermore, obligate mutualists had more SNPs under positive selection than facultative mutualists. Together, these results provide strong evidence that mutualism dependency impacts both the strength of coevolution and the rate of trait evolution.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"45 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}