Molecular biology and evolution最新文献

筛选
英文 中文
Extensive recombination suppression and genetic degeneration of a young ZW sex chromosome system in halfbeak fish. 半喙鱼幼性染色体ZW系统的广泛重组抑制和遗传退化。
IF 11 1区 生物学
Molecular biology and evolution Pub Date : 2025-06-24 DOI: 10.1093/molbev/msaf151
Teng-Fei Xing, Yu-Long Li, Hao Yang, Deborah Charlesworth, Jin-Xian Liu
{"title":"Extensive recombination suppression and genetic degeneration of a young ZW sex chromosome system in halfbeak fish.","authors":"Teng-Fei Xing, Yu-Long Li, Hao Yang, Deborah Charlesworth, Jin-Xian Liu","doi":"10.1093/molbev/msaf151","DOIUrl":"https://doi.org/10.1093/molbev/msaf151","url":null,"abstract":"<p><p>Sex chromosome systems have evolved independently across the tree of life, at different times in the past, and the evolutionary consequences of lacking recombination in sex-linked regions have been characterized in many old-established systems. However, empirical studies of young sex chromosomes are still scarce, especially in vertebrates. Integrating whole-genome sequencing data of two species of halfbeak fish, Hyporhamphus sajori and H. intermedius, we identified the sex determining system in H. sajori as female heterogamety, involving a large fully sex-linked ZW region (∼26 Mb) on chromosome 5. The closest relative, H. intermedius, has a small sex-linked region on a different chromosome, and shows male heterogamety, suggesting at least one turnover in this fish genus. The H. sajori sex-linked region includes two evolutionary strata, but the estimated Z-W divergence times are small, less than 3 million years for the older stratum, which is less than between the two species. Nevertheless, this evolutionarily young W-linked region is enriched with repetitive sequences, differs from the ancestral state by five inversions, and about one-third of its protein-coding genes have already become non-functional. Transcriptomic analysis suggests that some form of dosage compensation may already be evolving for some sex-linked genes.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The heterogametic transition in European Bufo toads switches the sex-linkage of key vertebrate sex-determination genes and associates with a large sex-chromosome-effect. 欧洲蟾蜍的异配子转变改变了关键脊椎动物性别决定基因的性别连锁,并与巨大的性染色体效应有关。
IF 11 1区 生物学
Molecular biology and evolution Pub Date : 2025-06-16 DOI: 10.1093/molbev/msaf142
Christophe Dufresnes, Pierre-André Crochet, Beata Rozenblut-Kościsty, Spartak N Litvinchuk, Nicolas Rodrigues, Nicolas Perrin, Daniel L Jeffries
{"title":"The heterogametic transition in European Bufo toads switches the sex-linkage of key vertebrate sex-determination genes and associates with a large sex-chromosome-effect.","authors":"Christophe Dufresnes, Pierre-André Crochet, Beata Rozenblut-Kościsty, Spartak N Litvinchuk, Nicolas Rodrigues, Nicolas Perrin, Daniel L Jeffries","doi":"10.1093/molbev/msaf142","DOIUrl":"https://doi.org/10.1093/molbev/msaf142","url":null,"abstract":"<p><p>Characterizing the diversity and lability of the amphibian sex chromosomes holds key to understand what drives sex chromosome turnovers and assess the role of sex-linked genes in reproductive isolation and speciation. Here we show that the heterogametic transition previously reported between the hybridizing toads Bufo bufo (ZW) and B. spinosus (XY) is non-homologous, potentially implicates key genes of the vertebrate sex determination cascade (SOX9, DMRT1, AMH), and is characterized by a much shorter ZW than XY segment. Integrating this information with published hybrid zone data suggests that both sex chromosomes resist interspecific introgression more than autosomes. These observations substantiate that sex chromosome turnovers preferentially involve chromosomes that host conserved sex-determining genes, imply heterochiasmy as a key factor of sex chromosome differentiation, and are consistent with a large sex-chromosome-effect, an empirical rule of speciation that is not expected with homomorphic sex chromosomes.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Widespread genetic signals of visual system adaptation in deepwater cichlid fishes. 深水慈鲷视觉系统适应的广泛遗传信号。
IF 11 1区 生物学
Molecular biology and evolution Pub Date : 2025-06-09 DOI: 10.1093/molbev/msaf147
Julia I Camacho García, Milan Malinsky, Domino A Joyce, M Emília Santos, Grégoire Vernaz, Maxon J Ngochera, Hannes Svardal
{"title":"Widespread genetic signals of visual system adaptation in deepwater cichlid fishes.","authors":"Julia I Camacho García, Milan Malinsky, Domino A Joyce, M Emília Santos, Grégoire Vernaz, Maxon J Ngochera, Hannes Svardal","doi":"10.1093/molbev/msaf147","DOIUrl":"https://doi.org/10.1093/molbev/msaf147","url":null,"abstract":"<p><p>The light environment exerts a profound selection pressure on the visual system, driving morphological and molecular adaptations that may also contribute to species diversification. Here, we investigate the evolution and genetic basis of visual system diversification in deepwater cichlid fishes of the genus Diplotaxodon. We find that Diplotaxodon exhibit the greatest eye size variation among Lake Malawi cichlids and that this variation is largely uncoupled from phylogeny, with various non-sister species sharing similar eye sizes. Using a combination of genome-wide association analysis across nine Diplotaxodon species, haplotype-based selection scans, and transcriptome analysis, we uncover consistent and widespread signatures of evolution in visual pathways, centered on green-sensitive opsins and throughout the phototransduction cascade, suggesting coordinated evolution of eye size and visual molecular pathways. Our findings underscore the role of visual system diversification in niche specialization within deepwater habitats and offer new insights into visual system evolution within this extraordinary cichlid radiation.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pervasive divergence in protein thermostability is mediated by both structural changes and cellular environments. 蛋白质热稳定性的普遍分化是由结构变化和细胞环境共同介导的。
IF 11 1区 生物学
Molecular biology and evolution Pub Date : 2025-06-06 DOI: 10.1093/molbev/msaf137
Nilima Walunjkar, Timothy Y Lai, Nasima Akhter, James H Miller, John Q Bettinger, Erin Marcus, Eric M Phizicky, Sina Ghaemmaghami, Justin C Fay
{"title":"Pervasive divergence in protein thermostability is mediated by both structural changes and cellular environments.","authors":"Nilima Walunjkar, Timothy Y Lai, Nasima Akhter, James H Miller, John Q Bettinger, Erin Marcus, Eric M Phizicky, Sina Ghaemmaghami, Justin C Fay","doi":"10.1093/molbev/msaf137","DOIUrl":"https://doi.org/10.1093/molbev/msaf137","url":null,"abstract":"<p><p>Temperature is a universal environmental constraint and organisms have evolved diverse mechanisms of thermotolerance. A central feature of thermophiles relative to mesophiles is a universal shift in protein stability, implying that it is a major constituent of thermotolerance. However, organisms have also evolved extensive buffering systems, such as those that disaggregate and refold denatured proteins and enable survival of heat shock. Here, we show that both cellular and protein structural changes contribute to divergence in protein thermostability between two closely related Saccharomyces species that differ by 8°C in their thermotolerance. Using thermal proteomic profiling we find that 85% of S. cerevisiae proteins are more stable than their S. uvarum homologs and there is a 1.6°C shift in average protein melting temperature. In an interspecific hybrid of the two species, S. cerevisiae proteins retain their thermostability, while the thermostability of their S. uvarum homologs is enhanced, indicating that cellular context contributes to protein stability differences. By purifying orthologous proteins, we show that amino acid substitutions underlie melting temperature differences for two proteins, Guk1 and Aha1. Amino acid substitutions are also computationally predicted to contribute to stability differences for most of the proteome. Our results imply that widespread changes in protein thermostability accompany the evolution of thermotolerance between closely related species.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Connectivity and adaptation patterns of the deep-sea ground-forming sponge Geodia hentscheli across its entire distribution. 深海成地海绵全分布的连通性与适应模式
IF 11 1区 生物学
Molecular biology and evolution Pub Date : 2025-06-06 DOI: 10.1093/molbev/msaf145
Sergi Taboada, Cristina Díez-Vives, Marta Turon, María Belén Arias, Carles Galià-Camps, Paco Cárdenas, Vasiliki Koutsouveli, Francisca Correia de Carvalho, Ellen Kenchington, Andrew J Davies, Shuangqiang Wang, Marta Martín-Huete, Emyr Martyn Roberts, Joana R Xavier, David Combosch, Ana Riesgo
{"title":"Connectivity and adaptation patterns of the deep-sea ground-forming sponge Geodia hentscheli across its entire distribution.","authors":"Sergi Taboada, Cristina Díez-Vives, Marta Turon, María Belén Arias, Carles Galià-Camps, Paco Cárdenas, Vasiliki Koutsouveli, Francisca Correia de Carvalho, Ellen Kenchington, Andrew J Davies, Shuangqiang Wang, Marta Martín-Huete, Emyr Martyn Roberts, Joana R Xavier, David Combosch, Ana Riesgo","doi":"10.1093/molbev/msaf145","DOIUrl":"https://doi.org/10.1093/molbev/msaf145","url":null,"abstract":"<p><p>Geodia hentscheli, a species forming sponge grounds in the North Atlantic and Arctic Oceans, is a common deep-sea organism, playing a fundamental role forming biogenic habitats. However, there is little information about gene flow and adaptation patterns of this species, which is crucial to develop effective management/conservation plans under current global change scenarios. Here, we generated ddRADseq data from 110 specimens of G. hentscheli, together with microbial profiling, transcriptomics and metatranscriptomics for a selection of specimens to investigate their genetic diversity, molecular connectivity and local adaptations. Sampling covered the species' entire distribution within a wide bathymetric range. We obtained 1,115 neutral SNPs and identified long distance genetic connectivity among regions separated 1,000s of km, but strong genetic structure segregating populations by depth at ca. 1,300 m, in line with our microbial analyses. Coalescent analyses inferred the split of these depth-related genetic entities ∼10 KYA, coincident with the last post-glacial maximum. Analyses of SNPs under selection, combined with transcriptomic and metatranscriptomic data highlight the presence of several sponge genes and microbial metabolic pathways involved in adaptation to depth, including heat shock proteins and fatty acids, amongst others. The physiological plasticity of the sponge and its microbiome as a function of depth suggest the existence of a host-microbiome metabolic compensation for G. hentscheli. This study provides a multiscale paradigmatic example of the Depth Differentiation Hypothesis, a phenomenon mainly caused by changes in environmental conditions at different depths, mainly related to the presence of water masses with different characteristics, that drive local adaptations.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Spatio-temporal tracking of three novel transposable element invasions in Drosophila melanogaster over the last 30 years. 近30年来黑胃果蝇三种新型转座因子入侵的时空追踪
IF 11 1区 生物学
Molecular biology and evolution Pub Date : 2025-06-06 DOI: 10.1093/molbev/msaf143
Riccardo Pianezza, Almorò Scarpa, Anna Haider, Sarah Signor, Robert Kofler
{"title":"Spatio-temporal tracking of three novel transposable element invasions in Drosophila melanogaster over the last 30 years.","authors":"Riccardo Pianezza, Almorò Scarpa, Anna Haider, Sarah Signor, Robert Kofler","doi":"10.1093/molbev/msaf143","DOIUrl":"https://doi.org/10.1093/molbev/msaf143","url":null,"abstract":"<p><p>Transposable elements (TEs) are repetitive sequences capable of mobilizing within genomes, exerting a sigfinificant influence on evolution throughout the tree of life. Using a novel approach that does not require prior knowledge of the sequence of repeats, we identified three novel TE invasions in D. melanogaster: McLE spread between 1990-2000, Souslik between 2009-2012, and Transib1 between 2013-2016. We recapitulate previous findings, revealing that a total of 11 TEs invaded D. melanogaster over the past two centuries. These 11 invasions increased the fly genome by ∼1 Mbp. Using data from over 1400 arthropod genomes, we provide evidence that these TE invasions were triggered by horizontal transfers, with D. simulans and species of the D. willistoni group acting as putative donors. Through the analysis of ∼600 short-read datasets spanning diverse geographic regions, we reveal the rapidity of TE invasions: Transib1 swiftly multiplied from three isolated epicenters in 2014 to all investigated populations in just two years. Our findings suggest that anthropogenic activities, which facilitate the range and population expansions of D. melanogaster, could have accelerated the rate of horizontal transposon transfer as well as the spread of the TEs into the worldwide population. Given the significant impact of TEs on evolution and the potential involvement of humans in their dispersal, our research has crucial implications for both evolution and ecology.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Accelerated Pseudogenization in the Ancient Endosymbionts of Giant Scale Insects. 巨型蚧虫古代内共生体的加速假原化。
IF 11 1区 生物学
Molecular biology and evolution Pub Date : 2025-06-04 DOI: 10.1093/molbev/msaf125
Jinyeong Choi, Pradeep Palanichamy, Hirotaka Tanaka, Takumasa Kondo, Matthew E Gruwell, Filip Husnik
{"title":"Accelerated Pseudogenization in the Ancient Endosymbionts of Giant Scale Insects.","authors":"Jinyeong Choi, Pradeep Palanichamy, Hirotaka Tanaka, Takumasa Kondo, Matthew E Gruwell, Filip Husnik","doi":"10.1093/molbev/msaf125","DOIUrl":"10.1093/molbev/msaf125","url":null,"abstract":"<p><p>Symbiotic microorganisms are subject to a complex interplay of environmental and population-genetic pressures that drive their gene loss. Despite the widely held perception that ancient symbionts have stable genomes, even tiny genomes experience ongoing pseudogenization. Whether these tiny genomes also experience bursts of rapid gene loss is, however, less understood. Giant scale insects (Monophlebidae) feed on plant sap and rely on the symbiotic bacterium Walczuchella, which provides them with essential nutrients. When compared with other ancient symbionts with similar genome sizes, such as Karelsulcia, Walczuchella's genome was previously reported as unusually pseudogene-rich (10% of coding sequences). However, this result was based on only one genome assembly, raising questions about the assembly quality or a recent ecological shift such as co-symbiont acquisition driving the gene loss. Here, we generated six complete genomes of Walczuchella from three genera of giant scales, each with distinct co-symbiotic partners. We show that all the genomes are highly degraded, and particularly genes related to the cellular envelope and energy metabolism seem to be undergoing pseudogenization. Apart from general mechanisms driving genome reduction, such as the long-term intracellular lifestyle with transmission bottlenecks, we hypothesize that a more profound loss of DNA replication and repair genes, together with recent co-obligate symbiont acquisitions, likely contribute to the accelerated degradation of Walczuchella genomes. Our results highlight that even ancient symbionts with small genomes can experience significant bursts of gene loss when stochastic processes erase a gene that accelerates gene loss or when the selection pressure changes such as after co-symbiont acquisition.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structural Changes in Gene Ontology Reveal Modular and Complex Representations of Biological Function. 基因本体的结构变化揭示了生物功能的模块化和复杂表征。
IF 11 1区 生物学
Molecular biology and evolution Pub Date : 2025-06-04 DOI: 10.1093/molbev/msaf148
Sergi Valverde, Blai Vidiella, Gemma I Martínez-Redondo, Salva Duran-Nebreda, Rosa Fernández, Aureliano Bombarely, Ana M Rojas, R Alexander Bentley
{"title":"Structural Changes in Gene Ontology Reveal Modular and Complex Representations of Biological Function.","authors":"Sergi Valverde, Blai Vidiella, Gemma I Martínez-Redondo, Salva Duran-Nebreda, Rosa Fernández, Aureliano Bombarely, Ana M Rojas, R Alexander Bentley","doi":"10.1093/molbev/msaf148","DOIUrl":"10.1093/molbev/msaf148","url":null,"abstract":"<p><p>The Gene Ontology is a central resource for representing biological knowledge, yet its internal structure is often treated as static-or as a black box-in computational analyses. Here, we examine 15 years of Gene Ontology evolution using network-based methods, revealing that Gene Ontology changes not only through incremental growth but also through punctuated, curator-driven restructuring. In particular, we document a major reorganization of the Cellular Component branch in 2019, where broad \"part\" terms were removed and the ontology was modularized into distinct domains for anatomical entities and protein-containing complexes. Semantic modularity aligns Gene Ontology with emerging frameworks such as the Common Anatomy Reference Ontology and Gene Ontology-Causal Activity Modeling, but also disrupts similarity metrics that rely solely on hierarchical proximity. More broadly, the restructuring of the cellular components branch consolidates a shift toward treating Gene Ontology as a multi-layer semantic network-a transformation rooted in a decade-long process of scientific and social consensus across institutions. These findings underscore the need for version-aware, multi-layer models to ensure reproducibility and interpretability-and to better represent biological function across compositional, spatial, and regulatory dimensions as ontologies continue to evolve.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A General Substitution Matrix for Structural Phylogenetics. 结构系统发育的一般替换矩阵。
IF 11 1区 生物学
Molecular biology and evolution Pub Date : 2025-06-04 DOI: 10.1093/molbev/msaf124
Sriram G Garg, Georg K A Hochberg
{"title":"A General Substitution Matrix for Structural Phylogenetics.","authors":"Sriram G Garg, Georg K A Hochberg","doi":"10.1093/molbev/msaf124","DOIUrl":"10.1093/molbev/msaf124","url":null,"abstract":"<p><p>Sequence-based maximum likelihood phylogenetics is a widely used method for inferring evolutionary relationships, which has illuminated the evolutionary histories of proteins and the organisms that harbor them. However, modern implementations with sophisticated models of sequence evolution struggle to resolve deep evolutionary relationships, which can be obscured by excessive sequence divergence and substitution saturation. Structural phylogenetics has emerged as a promising alternative because protein structure evolves much more slowly than protein sequences. Recent developments in protein structure prediction using AI have made it possible to predict protein structures for entire protein families and then to translate these structures into a sequence representation-the 3Di structural alphabet-that can in theory be directly fed into existing sequence-based phylogenetic software. To unlock the full potential of this idea, however, requires the inference of a general substitution matrix for structural phylogenetics, which has so far been missing. Here, we infer this matrix from large datasets of protein structures and show that it results in a better fit to empirical datasets than previous approaches. We then use this matrix to re-visit the question of the root of the tree of life. Using structural phylogenies of universal paralogs, we provide the first unambiguous evidence for a root between archaea and bacteria. Finally, we discuss some practical and conceptual limitations of structural phylogenetics. Our 3Di substitution matrix provides a starting point for revisiting many deep phylogenetic problems that have so far been extremely difficult to solve.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tripartite Loops Reverse Antibiotic Resistance. 三环逆转抗生素耐药性。
IF 11 1区 生物学
Molecular biology and evolution Pub Date : 2025-06-04 DOI: 10.1093/molbev/msaf115
Farhan R Chowdhury, Brandon L Findlay
{"title":"Tripartite Loops Reverse Antibiotic Resistance.","authors":"Farhan R Chowdhury, Brandon L Findlay","doi":"10.1093/molbev/msaf115","DOIUrl":"10.1093/molbev/msaf115","url":null,"abstract":"<p><p>Antibiotic resistance threatens to undo many of the advancements of modern medicine. A slow antibiotic development pipeline makes it impossible to outpace bacterial evolution, making alternative strategies essential to combat resistance. In this study, we introduce cyclic antibiotic regimens composed of 3 drugs or \"tripartite loops\" to contain resistance within a closed drug cycle. Through 424 discrete adaptive laboratory evolution experiments we show that as bacteria sequentially evolve resistance to the drugs in a loop, they continually trade their past resistance for fitness gains, reverting back to sensitivity. Through fitness and genomic analyses, we find that tripartite loops guide bacterial strains toward evolutionary paths that mitigate fitness costs and reverse resistance to component drugs in the loops and drive levels of resensitization not achievable through previously suggested pairwise regimens. We then apply this strategy to reproducibly resensitize or eradicate 4 drug-resistant clinical isolates over the course of 216 evolutionary experiments. Resensitization occurrs even when bacteria adapted through plasmid-bound mutations instead of chromosomal changes. Combined, these findings outline a sequential antibiotic regimen with high resensitization frequencies, which may improve the clinical longevity of existing antibiotics even in the face of antibiotic resistance.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信