PLoS Biology最新文献

{"title":"Targeted DamID detects cell-type-specific histone modifications in intact tissues or organisms.","authors":"Jelle van den Ameele, Manuel Trauner, Eva Hörmanseder, Alex P A Donovan, Oriol Llorà-Batlle, Seth W Cheetham, Robert Krautz, Rebecca Yakob, Anna Malkowska, John B Gurdon, Andrea H Brand","doi":"10.1371/journal.pbio.3002944","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002944","url":null,"abstract":"<p><p>Histone modifications play a key role in regulating gene expression and cell fate during development and disease. Current methods for cell-type-specific genome-wide profiling of histone modifications require dissociation and isolation of cells and are not compatible with all tissue types. Here we adapt Targeted DamID (TaDa) to recognize specific histone marks, by fusing chromatin-binding proteins or single-chain antibodies to Dam, an Escherichia coli DNA adenine methylase. When combined with TaDa, this enables cell-type-specific chromatin profiling in intact tissues or organisms. We first profiled H3K4me3, H3K9ac, H3K27me3 and H4K20me1 in vivo in neural stem cells of the developing Drosophila brain. Next, we mapped cell-type-specific H3K4me3, H3K9ac and H4K20me1 distributions in the developing mouse brain. Finally, we injected RNA encoding DamID constructs into 1-cell stage Xenopus embryos to profile H3K4me3 distribution during gastrulation and neurulation. These results illustrate the versatility of TaDa to profile cell-type-specific histone marks throughout the genome in diverse model systems.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3002944"},"PeriodicalIF":9.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606153","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}

{"title":"Genetic, developmental, and neural changes underlying the evolution of butterfly mate preference.","authors":"Nicholas W VanKuren, Nathan P Buerkle, Wei Lu, Erica L Westerman, Alexandria K Im, Darli Massardo, Laura Southcott, Stephanie E Palmer, Marcus R Kronforst","doi":"10.1371/journal.pbio.3002989","DOIUrl":"10.1371/journal.pbio.3002989","url":null,"abstract":"<p><p>Many studies have linked genetic variation to behavior, but few connect to the intervening neural circuits that underlie the arc from sensation to action. Here, we used a combination of genome-wide association (GWA), developmental gene expression, and photoreceptor electrophysiology to investigate the architecture of mate choice behavior in Heliconius cydno butterflies, a clade where males identify preferred mates based on wing color patterns. We first found that the GWA variants most strongly associated with male mate choice were tightly linked to the gene controlling wing color in the K locus, consistent with previous mapping efforts. RNA-seq across developmental time points then showed that seven genes near the top GWA peaks were differentially expressed in the eyes, optic lobes, or central brain of white and yellow H. cydno males, many of which have known functions in the development and maintenance of synaptic connections. In the visual system of these butterflies, we identified a striking physiological difference between yellow and white males that could provide an evolutionarily labile circuit motif in the eye to rapidly switch behavioral preference. Using single-cell electrophysiology recordings, we found that some ultraviolet (UV)-sensitive photoreceptors receive inhibition from long-wavelength photoreceptors in the male eye. Surprisingly, the proportion of inhibited UV photoreceptors was strongly correlated with male wing color, suggesting a difference in the early stages of visual processing that could plausibly influence courtship decisions. We discuss potential links between candidate genes and this physiological signature, and suggest future avenues for experimental work. Taken together, our results support the idea that alterations to the evolutionarily labile peripheral nervous system, driven by genetic and gene expression differences, can significantly and rapidly alter essential behaviors.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3002989"},"PeriodicalIF":9.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606953","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}

{"title":"Signals from the niche promote distinct modes of translation initiation to control stem cell differentiation and renewal in the Drosophila testis.","authors":"Ruoxu Wang, Mykola Roiuk, Freya Storer, Aurelio A Teleman, Marc Amoyel","doi":"10.1371/journal.pbio.3003049","DOIUrl":"10.1371/journal.pbio.3003049","url":null,"abstract":"<p><p>Stem cells have the unique ability among adult cells to give rise to cells of different identities. To do so, they must change gene expression in response to environmental signals. Much work has focused on how transcription is regulated to achieve these changes; however, in many cell types, transcripts and proteins correlate poorly, indicating that post-transcriptional regulation is important. To assess how translational control can influence stem cell fate, we use the Drosophila testis as a model. The testis niche secretes a ligand to activate the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway in two stem cell populations, germline stem cells (GSCs) and somatic cyst stem cells (CySCs). We find that global translation rates are high in CySCs and decrease during differentiation, and that JAK/STAT signaling regulates translation. To determine how translation was regulated, we knocked down translation initiation factors and found that the cap binding complex, eIF4F, is dispensable in differentiating cells, but is specifically required in CySCs for self-renewal, acting downstream of JAK/STAT activity. Moreover, we identify eIF3d1 as a key regulator of CySC fate, and show that two eIF3d1 residues subject to regulation by phosphorylation are critical to maintain CySC self-renewal. We further show that Casein Kinase II (CkII), which controls eIF3d1 phosphorylation, influences the binding of eIF3d and eIF4F in mammalian cells, and that CkII expression is sufficient to restore CySC function in the absence of JAK/STAT. We propose a model in which niche signals regulate a specific translation programme in which only some mRNAs are translated. The mechanism we identify allows stem cells to switch between modes of translation, adding a layer of regulation on top of transcription and providing cells with the ability to rapidly change gene expression upon receiving external stimuli.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3003049"},"PeriodicalIF":9.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606123","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}

{"title":"Structural characterization of the ABC transporter DppABCDF in Escherichia coli reveals insights into dipeptide acquisition.","authors":"Panpan Li, Manfeng Zhang, Yihua Huang","doi":"10.1371/journal.pbio.3003026","DOIUrl":"10.1371/journal.pbio.3003026","url":null,"abstract":"<p><p>The prokaryote-specific ATP-binding cassette (ABC) peptide transporters are involved in various physiological processes and plays an important role in transporting naturally occurring antibiotics across the membrane to their intracellular targets. The dipeptide transporter DppABCDF in Gram-negative bacteria is composed of five distinct subunits, yet its assembly and underlying peptide import mechanism remain elusive. Here, we report the cryo-EM structures of the DppBCDF translocator from Escherichia coli in both its apo form and in complexes bound to nonhydrolyzable or slowly hydrolyzable ATP analogs (AMPPNP and ATPγS), as well as the ATPγS-bound DppABCDF full transporter. Unlike the reported heterotrimeric Mycobacterium tuberculosis DppBCD translocator, the E. coli DppBCDF translocator is a heterotetramer, with a [4Fe-4S] cluster at the C-terminus of each ATPase subunit. Structural studies reveal that ATPγS/AMPPNP-bound DppBCDF adopts an inward-facing conformation, similar to that of apo-DppBCDF, with only one ATPγS or AMPPNP molecule bound to DppF. By contrast, ATPγS-bound DppABCDF adopts an outward-facing conformation, with two ATPγS molecules glueing DppD and DppF at the interface. Consistent with structural observations, ATPase activity assays show that the DppBCDF translocator itself is inactive and its activation requires concurrent binding of DppA and ATP. In addition, bacterial complementation experiments imply that a unique periplasmic scoop motif in DppB may play important roles in ensuring dipeptide substrates import across the membrane, presumably by preventing dipeptide back-and-forth binding to DppA and avoiding dipeptides escaping into the periplasm upon being released from DppA.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3003026"},"PeriodicalIF":9.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575754","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}

{"title":"Members of the DIP and Dpr adhesion protein families use cis inhibition to shape neural development in Drosophila.","authors":"Nicholas C Morano, Davys H Lopez, Hagar Meltzer, Alina P Sergeeva, Phinikoula S Katsamba, Kevin D Rostam, Himanshu Pawankumar Gupta, Jordan E Becker, Bavat Bornstein, Filip Cosmanescu, Oren Schuldiner, Barry Honig, Richard S Mann, Lawrence Shapiro","doi":"10.1371/journal.pbio.3003030","DOIUrl":"10.1371/journal.pbio.3003030","url":null,"abstract":"<p><p>In Drosophila, two interacting adhesion protein families, Defective proboscis responses (Dprs) and Dpr interacting proteins (DIPs), coordinate the assembly of neural networks. While intercellular DIP::Dpr interactions have been well characterized, DIPs and Dprs are often co-expressed within the same cells, raising the question as to whether they also interact in cis. We show, in cultured cells and in vivo, that DIP-α and DIP-δ can interact in cis with their ligands, Dpr6/10 and Dpr12, respectively. When co-expressed in cis with their cognate partners, these Dprs regulate the extent of trans binding, presumably through competitive cis interactions. We demonstrate the neurodevelopmental effects of cis inhibition in fly motor neurons and in the mushroom body. We further show that a long disordered region of DIP-α at the C-terminus is required for cis but not trans interactions, likely because it alleviates geometric constraints on cis binding. Thus, the balance between cis and trans interactions plays a role in controlling neural development.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3003030"},"PeriodicalIF":9.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605558","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}

{"title":"Mucilage produced by aerial roots hosts diazotrophs that provide nitrogen in Sorghum bicolor.","authors":"Rafael E Venado, Jennifer Wilker, Vânia C S Pankievicz, Valentina Infante, April MacIntyre, Emily S A Wolf, Saddie Vela, Fletcher Robbins, Paulo Ivan Fernandes-Júnior, Wilfred Vermerris, Jean-Michel Ané","doi":"10.1371/journal.pbio.3003037","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003037","url":null,"abstract":"<p><p>Sorghum (Sorghum bicolor) is an important food, feed, and fodder crop worldwide and is gaining popularity as an energy crop due to its high potential for biomass production. Some sorghum accessions develop many aerial roots and produce an abundant carbohydrate-rich mucilage after rain. This aerial root mucilage is similar to that observed in landraces of maize (Zea mays) from southern Mexico, which have been previously shown to host diazotrophs. In this study, we characterized the aerial root development of several sorghum accessions and the impact of humidity on this trait. We conducted a microbiome study of the aerial root mucilage of maize and sorghum and isolated numerous diazotrophs from field sorghum mucilage. We observed that the prevailing phyla in the mucilage were Pseudomonadota, Bacteroidota, and Bacillota. However, bacterial abundances varied based on the genotype and the location. Using acetylene reduction, 15N2 gas feeding, and 15N isotope dilution assays, we confirmed that these sorghum accessions can acquire about 40% of their nitrogen from the atmosphere through these associations on aerial roots. Nitrogen fixation in sorghum aerial root mucilage offers a promising avenue to reduce reliance on synthetic fertilizers and promote sustainable agricultural practices for food, feed, fodder, and bioenergy production.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3003037"},"PeriodicalIF":9.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597731","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}

{"title":"New solutions for antibiotic discovery: Prioritizing microbial biosynthetic space using ecology and machine learning.","authors":"Marnix H Medema, Gilles P van Wezel","doi":"10.1371/journal.pbio.3003058","DOIUrl":"10.1371/journal.pbio.3003058","url":null,"abstract":"<p><p>With the explosive increase in genome sequence data, perhaps the major challenge in natural-product-based drug discovery is the identification of gene clusters most likely to specify new chemistry and bioactivities. We discuss the challenges and state-of-the-art of antibiotic discovery based on ecological principles, genome mining and artificial intelligence.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 2","pages":"e3003058"},"PeriodicalIF":9.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527981","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}

{"title":"Incomplete recombination suppression fuels extensive haplotype diversity in a butterfly colour pattern supergene.","authors":"Rishi De-Kayne, Ian J Gordon, Reinier F Terblanche, Steve Collins, Kennedy Saitoti Omufwoko, Dino J Martins, Simon H Martin","doi":"10.1371/journal.pbio.3003043","DOIUrl":"10.1371/journal.pbio.3003043","url":null,"abstract":"<p><p>Supergenes can evolve when recombination-suppressing mechanisms like inversions promote co-inheritance of alleles at two or more polymorphic loci that affect a complex trait. Theory shows that such genetic architectures can be favoured under balancing selection or local adaptation in the face of gene flow, but they can also bring costs associated with reduced opportunities for recombination. These costs may in turn be offset by rare 'gene flux' between inverted and ancestral haplotypes, with a range of possible outcomes. We aimed to shed light on these processes by investigating the 'BC supergene', a large genomic region comprising multiple rearrangements associated with three distinct wing colour morphs in Danaus chrysippus, a butterfly known as the African monarch, African queen and plain tiger. Using whole-genome resequencing data from 174 individuals, we first confirm the effects of BC on wing colour pattern: background melanism is associated with SNPs in the promoter region of yellow, within an inverted subregion of the supergene, while forewing tip pattern is most likely associated with copy-number variation in a separate subregion of the supergene. We then show that haplotype diversity within the supergene is surprisingly extensive: there are at least six divergent haplotype groups that experience suppressed recombination with respect to each other. Despite high divergence between these haplotype groups, we identify an unexpectedly large number of natural recombinant haplotypes. Several of the inferred crossovers occurred between adjacent inversion 'modules', while others occurred within inversions. Furthermore, we show that new haplotype groups have arisen through recombination between two pre-existing ones. Specifically, an allele for dark colouration in the promoter of yellow has recombined into distinct haplotype backgrounds on at least two separate occasions. Overall, our findings paint a picture of dynamic evolution of supergene haplotypes, fuelled by incomplete recombination suppression.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 2","pages":"e3003043"},"PeriodicalIF":9.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11918383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528143","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}

{"title":"Innovations in noninvasive sensory stimulation treatments to combat Alzheimer's disease.","authors":"Jung M Park, Li-Huei Tsai","doi":"10.1371/journal.pbio.3003046","DOIUrl":"10.1371/journal.pbio.3003046","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting millions worldwide. There is no known cure for AD, highlighting an urgent need for new, innovative treatments. Recent studies have shed light on a promising, noninvasive approach using sensory stimulation as a potential therapy for AD. Exposing patients to light and sound pulses at a frequency of 40 hertz induces brain rhythms in the gamma frequency range that are important for healthy brain activity. Using this treatment in animal models, we are now beginning to understand the molecular, cellular, and circuit-level changes that underlie improvements in disease pathology, cognition, and behavior. A mechanistic understanding of the basic biology that underlies the 40-hertz treatment will inform ongoing clinical trials that offer a promising avenue of treatment without the side effects and high costs typically associated with pharmacological interventions. Concurrent advancements in neurotechnology that can also noninvasively stimulate healthy brain rhythms are illuminating new possibilities for alternative therapies. Altogether, these noninvasive approaches could herald a new era in treating AD, making them a beacon of hope for patients, families, and caregivers facing the challenges of this debilitating condition.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 2","pages":"e3003046"},"PeriodicalIF":9.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528145","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}

{"title":"Evolutionary origin of lubricated joints at the dawn of jawed vertebrates.","authors":"J Gage Crump","doi":"10.1371/journal.pbio.3003044","DOIUrl":"10.1371/journal.pbio.3003044","url":null,"abstract":"<p><p>The evolutionary origin of the lubricated joints that allow our interconnected skeleton to swivel, rotate, and bend has remained a mystery. A new comparative study of joints in PLOS Biology points to lubricated joints arising in the earliest jawed vertebrates.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 2","pages":"e3003044"},"PeriodicalIF":9.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517162","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}