PLoS Biology最新文献

{"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}

{"title":"Synovial joints were present in the common ancestor of jawed fish but lacking in jawless fish.","authors":"Neelima Sharma, Yara Haridy, Neil Shubin","doi":"10.1371/journal.pbio.3002990","DOIUrl":"10.1371/journal.pbio.3002990","url":null,"abstract":"<p><p>Synovial joints, characterized by reciprocally congruent and lubricated articular surfaces separated by a cavity, can simultaneously provide mobility and load bearing. Here, we study the early evolution of synovial joints by examining the morphological, genetic, and molecular features required for the development and function of the joints in elasmobranchs and cyclostomes. We show the presence of cavitated and articulated joints in the skeleton of elasmobranchs, such as the little skate (Leucoraja erinacea) and bamboo shark (Chiloscyllium plagiosum). However, our results do not support the presence of articular cavities between cartilaginous elements in cyclostomes such as sea lampreys (Petromyozon marinus) and hagfish (Myxine glutinosa). Immunostaining reveals the expression of lubrication-related proteoglycans like aggrecan and glycoproteins such as hyaluronic acid receptor (CD44) at the articular surfaces in little skates. Analysis of joint development in little skate embryos shows the expression of growth differentiation factor-5 (Gdf5) and β-catenin at the joint interzones like tetrapods. Muscle paralysis in little skate embryos leads to joint fusion, suggesting that muscle activity is necessary for the formation of synovial cavity and development of normal articular surfaces, in a manner similar to zebrafish and tetrapods. Together, these data suggest that synovial joints originated in the common ancestor of extant gnathostomes. A review of fossils from the extinct clades along the gnathostome stem suggests that joints with reciprocally articulating surfaces arose in the dermal skeleton of the common ancestor of all jawed vertebrates. Synovial joints in cartilaginous tissue were a subsequent gnathostome innovation.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 2","pages":"e3002990"},"PeriodicalIF":9.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11856278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143504979","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":"RIPK1 is required for ZBP1-driven necroptosis in human cells.","authors":"Oluwamuyiwa T Amusan, Shuqi Wang, Chaoran Yin, Heather S Koehler, Yixun Li, Tencho Tenev, Rebecca Wilson, Benjamin Bellenie, Ting Zhang, Jian Wang, Chang Liu, Kim Seong, Seyedeh L Poorbaghi, Joseph Yates, Yuchen Shen, Jason W Upton, Pascal Meier, Siddharth Balachandran, Hongyan Guo","doi":"10.1371/journal.pbio.3002845","DOIUrl":"10.1371/journal.pbio.3002845","url":null,"abstract":"<p><p>Necroptosis initiated by the host sensor Z-NA binding protein 1 (ZBP1) is essential for host defense against a growing number of viruses, including herpes simplex virus 1 (HSV-1). Studies with HSV-1 and other necroptogenic stimuli in murine settings have suggested that ZBP1 triggers necroptosis by directly complexing with the kinase RIPK3. Whether this is also the case in human cells, or whether additional co-factors are needed for ZBP1-mediated necroptosis, is unclear. Here, we show that ZBP1-induced necroptosis in human cells requires RIPK1. We have found that RIPK1 is essential for forming a stable and functional ZBP1-RIPK3 complex in human cells, but is dispensable for the formation of the equivalent murine complex. The receptor-interacting protein (RIP) homology interaction motif (RHIM) in RIPK3 is responsible for this difference between the 2 species, because replacing the RHIM in human RIPK3 with the RHIM from murine RIPK3 is sufficient to overcome the requirement for RIPK1 in human cells. These observations describe a critical mechanistic difference between mice and humans in how ZBP1 engages in necroptosis, with important implications for treating human diseases.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 2","pages":"e3002845"},"PeriodicalIF":9.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473034","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":"Caspase 3 and caspase 7 promote cytoprotective autophagy and the DNA damage response during non-lethal stress conditions in human breast cancer cells.","authors":"Gayathri Samarasekera, Nancy E Go, Courtney Choutka, Jing Xu, Yuka Takemon, Jennifer Chan, Michelle Chan, Shivani Perera, Samuel Aparicio, Gregg B Morin, Marco A Marra, Suganthi Chittaranjan, Sharon M Gorski","doi":"10.1371/journal.pbio.3003034","DOIUrl":"10.1371/journal.pbio.3003034","url":null,"abstract":"<p><p>Cell stress adaptation plays a key role in normal development and in various diseases including cancer. Caspases are activated in response to cell stress, and growing evidence supports their function in non-apoptotic cellular processes. A role for effector caspases in promoting stress-induced cytoprotective autophagy was demonstrated in Drosophila, but has not been explored in the context of human cells. We found a functionally conserved role for effector caspase 3 (CASP3) and caspase 7 (CASP7) in promoting starvation or proteasome inhibition-induced cytoprotective autophagy in human breast cancer cells. The loss of CASP3 and CASP7 resulted in an increase in PARP1 cleavage, reduction in LC3B and ATG7 transcript levels, and a reduction in H2AX phosphorylation, consistent with a block in autophagy and DNA damage-induced stress response pathways. Surprisingly, in non-lethal cell stress conditions, CASP7 underwent non-canonical processing at two calpain cleavage sites flanking a PARP1 exosite, resulting in stable CASP7-p29/p30 fragments. Expression of CASP7-p29/p30 fragment(s) could rescue H2AX phosphorylation in the CASP3 and CASP7 double knockout background. Strikingly, yet consistent with these phenotypes, the loss of CASP3 and CASP7 exhibited synthetic lethality with BRCA1 loss. These findings support a role for human caspases in stress adaptation through PARP1 modulation and reveal new therapeutic avenues for investigation.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 2","pages":"e3003034"},"PeriodicalIF":9.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473029","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":"Macrophage invasion into the Drosophila brain requires JAK/STAT-dependent MMP activation in the blood-brain barrier.","authors":"Bente Winkler, Dominik Funke, Christian Klämbt","doi":"10.1371/journal.pbio.3003035","DOIUrl":"10.1371/journal.pbio.3003035","url":null,"abstract":"<p><p>The central nervous system is well-separated from external influences by the blood-brain barrier. Upon surveillance, infection or neuroinflammation, however, peripheral immune cells can enter the brain where they often cause detrimental effects. To invade the brain, immune cells not only have to breach cellular barriers, but they also need to traverse associated extracellular matrix barriers. Neither in vertebrates nor in invertebrates is it fully understood how these processes are molecularly controlled. We recently established Drosophila melanogaster as a model to elucidate peripheral immune cell invasion into the brain. Here, we show that neuroinflammation leads to the expression of Unpaired cytokines that activate the JAK/STAT signaling pathway in glial cells of the blood-brain barrier. This in turn triggers the expression of matrix metalloproteinases enabling remodeling of the extracellular matrix enclosing the fly brain and a subsequent invasion of immune cells into the brain. Our study demonstrates conserved mechanisms underlying immune cell invasion of the nervous system in invertebrates and vertebrates and could, thus, further contribute to understanding of JAK/STAT signaling during neuroinflammation.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 2","pages":"e3003035"},"PeriodicalIF":9.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469685","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":"Neural development goes retro: Gags as essential modulators of synapse formation.","authors":"Yung-Heng Chang, Josh Dubnau","doi":"10.1371/journal.pbio.3003032","DOIUrl":"10.1371/journal.pbio.3003032","url":null,"abstract":"<p><p>Neurodevelopment requires dynamic control of synapse number. A new study in PLOS Biology reveals that the gag protein of Copia, an active retrotransposon, forms virus-like capsids that transfer its own RNA across the Drosophila neuromuscular junction. Here, Copia acts antagonistically with Arc, another retrotransposon gag protein, to regulate synapse formation.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 2","pages":"e3003032"},"PeriodicalIF":9.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11838888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460202","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":"Capsid transfer of the retrotransposon Copia controls structural synaptic plasticity in Drosophila.","authors":"P Githure M'Angale, Adrienne Lemieux, Yumeng Liu, Shuhao Wang, Max Zinter, Gimena Alegre, Alfred Simkin, Vivian Budnik, Brian A Kelch, Travis Thomson","doi":"10.1371/journal.pbio.3002983","DOIUrl":"10.1371/journal.pbio.3002983","url":null,"abstract":"<p><p>Transposons are parasitic genome elements that can also serve as raw material for the evolution of new cellular functions. However, how retrotransposons are selected and domesticated by host organisms to modulate synaptic plasticity remains largely unknown. Here, we show that the Ty1 retrotransposon Copia forms virus-like capsids in vivo and transfers between cells. Copia is enriched at the Drosophila neuromuscular junction (NMJ) and transported across synapses, and disrupting its expression promotes both synapse development and structural synaptic plasticity. We show that proper synaptic plasticity is maintained in Drosophila by the balance of Copia and the Arc1 (activity-regulated cytoskeleton-associated protein) homolog. High-resolution cryogenic-electron microscopy imaging shows that the structure of the Copia capsid has a large capacity and pores like retroviruses but is distinct from domesticated capsids such as dArc1. Our results suggest a fully functional transposon mediates synaptic plasticity, possibly representing an early stage of domestication of a retrotransposon.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 2","pages":"e3002983"},"PeriodicalIF":9.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450740","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":"The cholesterol 24-hydroxylase CYP46A1 promotes α-synuclein pathology in Parkinson's disease.","authors":"Lijun Dai, Jiannan Wang, Lanxia Meng, Xingyu Zhang, Tingting Xiao, Min Deng, Guiqin Chen, Jing Xiong, Wei Ke, Zhengyuan Hong, Lihong Bu, Zhentao Zhang","doi":"10.1371/journal.pbio.3002974","DOIUrl":"10.1371/journal.pbio.3002974","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative disease characterized by the death of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies that are composed of aggregated α-synuclein (α-Syn). However, the factors that regulate α-Syn pathology and nigrostriatal dopaminergic degeneration remain poorly understood. Previous studies demonstrate cholesterol 24-hydroxylase (CYP46A1) increases the risk for PD. Moreover, 24-hydroxycholesterol (24-OHC), a brain-specific oxysterol that is catalyzed by CYP46A1, is elevated in the cerebrospinal fluid of PD patients. Herein, we show that the levels of CYP46A1 and 24-OHC are elevated in PD patients and increase with age in a mouse model. Overexpression of CYP46A1 intensifies α-Syn pathology, whereas genetic removal of CYP46A1 attenuates α-Syn neurotoxicity and nigrostriatal dopaminergic degeneration in the brain. Moreover, supplementation with exogenous 24-OHC exacerbates the mitochondrial dysfunction induced by α-Syn fibrils. Intracerebral injection of 24-OHC enhances the spread of α-Syn pathology and dopaminergic neurodegeneration via elevated X-box binding protein 1 (XBP1) and lymphocyte-activation gene 3 (LAG3) levels. Thus, elevated CYP46A1 and 24-OHC promote neurotoxicity and the spread of α-Syn via the XBP1-LAG3 axis. Strategies aimed at inhibiting the CYP46A1-24-OHC axis and LAG3 could hold promise as disease-modifying therapies for PD.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 2","pages":"e3002974"},"PeriodicalIF":9.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450745","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}