PLoS Biology最新文献

{"title":"Plasmodium NEK1 coordinates MTOC organisation and kinetochore attachment during rapid mitosis in male gamete formation","authors":"Mohammad Zeeshan, Ravish Rashpa, David J. Ferguson, George Mckeown, Raushan Nugmanova, Amit K. Subudhi, Raphael Beyeler, Sarah L. Pashley, Robert Markus, Declan Brady, Magali Roques, Andrew R. Bottrill, Andrew M. Fry, Arnab Pain, Sue Vaughan, Anthony A. Holder, Eelco C. Tromer, Mathieu Brochet, Rita Tewari","doi":"10.1371/journal.pbio.3002802","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002802","url":null,"abstract":"Mitosis is an important process in the cell cycle required for cells to divide. Never in mitosis (NIMA)-like kinases (NEKs) are regulators of mitotic functions in diverse organisms. <jats:italic>Plasmodium</jats:italic> spp., the causative agent of malaria is a divergent unicellular haploid eukaryote with some unusual features in terms of its mitotic and nuclear division cycle that presumably facilitate proliferation in varied environments. For example, during the sexual stage of male gametogenesis that occurs within the mosquito host, an atypical rapid closed endomitosis is observed. Three rounds of genome replication from 1N to 8N and successive cycles of multiple spindle formation and chromosome segregation occur within 8 min followed by karyokinesis to generate haploid gametes. Our previous <jats:italic>Plasmodium berghei</jats:italic> kinome screen identified 4 <jats:italic>Nek</jats:italic> genes, of which 2, NEK2 and NEK4, are required for meiosis. NEK1 is likely to be essential for mitosis in asexual blood stage schizogony in the vertebrate host, but its function during male gametogenesis is unknown. Here, we study NEK1 location and function, using live cell imaging, ultrastructure expansion microscopy (U-ExM), and electron microscopy, together with conditional gene knockdown and proteomic approaches. We report spatiotemporal NEK1 location in real-time, coordinated with microtubule organising centre (MTOC) dynamics during the unusual mitoses at various stages of the <jats:italic>Plasmodium</jats:italic> spp. life cycle. Knockdown studies reveal NEK1 to be an essential component of the MTOC in male cell differentiation, associated with rapid mitosis, spindle formation, and kinetochore attachment. These data suggest that <jats:italic>P</jats:italic>. <jats:italic>berghei</jats:italic> NEK1 kinase is an important component of MTOC organisation and essential regulator of chromosome segregation during male gamete formation.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142195499","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":"The genetic basis of the kākāpō structural color polymorphism suggests balancing selection by an extinct apex predator.","authors":"Lara Urban,Anna W Santure,Lydia Uddstrom,Andrew Digby,Deidre Vercoe,Daryl Eason,Jodie Crane,,Matthew J Wylie,Tāne Davis,Marissa F LeLec,Joseph Guhlin,Simon Poulton,Jon Slate,Alana Alexander,Patricia Fuentes-Cross,Peter K Dearden,Neil J Gemmell,Farhan Azeem,Marvin Weyland,Harald G L Schwefel,Cock van Oosterhout,Hernán E Morales","doi":"10.1371/journal.pbio.3002755","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002755","url":null,"abstract":"The information contained in population genomic data can tell us much about the past ecology and evolution of species. We leveraged detailed phenotypic and genomic data of nearly all living kākāpō to understand the evolution of its feather color polymorphism. The kākāpō is an endangered and culturally significant parrot endemic to Aotearoa New Zealand, and the green and olive feather colorations are present at similar frequencies in the population. The presence of such a neatly balanced color polymorphism is remarkable because the entire population currently numbers less than 250 birds, which means it has been exposed to severe genetic drift. We dissected the color phenotype, demonstrating that the two colors differ in their light reflectance patterns due to differential feather structure. We used quantitative genomics methods to identify two genetic variants whose epistatic interaction can fully explain the species' color phenotype. Our genomic forward simulations show that balancing selection might have been pivotal to establish the polymorphism in the ancestrally large population, and to maintain it during population declines that involved a severe bottleneck. We hypothesize that an extinct apex predator was the likely agent of balancing selection, making the color polymorphism in the kākāpō a \"ghost of selection past.\"","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142195495","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":"Fixing science means an end to gaming the system","authors":"Nicholas J. L. Brown","doi":"10.1371/journal.pbio.3002816","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002816","url":null,"abstract":"During the last decade, there has been a substantial acceleration in the open science movement. Most people would probably hope to have seen signs of positive change in that time, yet it seems that the process of improving the practice of science is moving at a glacial pace.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142195502","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":"To transfer mitochondria or not to transfer mitochondria: ADP does the trick","authors":"Jaromir Novak, Jiri Neuzil","doi":"10.1371/journal.pbio.3002754","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002754","url":null,"abstract":"Horizontal mitochondrial transfer (HMT) has emerged as a novel phenomenon in cell biology, but it is unclear how this process of intercellular movement of mitochondria is regulated. A new study in <jats:italic>PLOS Biology</jats:italic> reports that ADP released by stressed cells is a signal that triggers HMT.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142225120","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":"The kinase Rio1 and a ribosome collision-dependent decay pathway survey the integrity of 18S rRNA cleavage","authors":"Melissa D. Parker, Elise S. Brunk, Adam J. Getzler, Katrin Karbstein","doi":"10.1371/journal.pbio.3001767","DOIUrl":"https://doi.org/10.1371/journal.pbio.3001767","url":null,"abstract":"The 18S rRNA sequence is highly conserved, particularly at its 3′-end, which is formed by the endonuclease Nob1. How Nob1 identifies its target sequence is not known, and in vitro experiments have shown Nob1 to be error-prone. Moreover, the sequence around the 3′-end is degenerate with similar sites nearby. Here, we used yeast genetics, biochemistry, and next-generation sequencing to investigate a role for the ATPase Rio1 in monitoring the accuracy of the 18S rRNA 3′-end. We demonstrate that Nob1 can miscleave its rRNA substrate and that miscleaved rRNA accumulates upon bypassing the Rio1-mediated quality control (QC) step, but not in healthy cells with intact QC mechanisms. Mechanistically, we show that Rio1 binding to miscleaved rRNA is weaker than its binding to accurately processed 18S rRNA. Accordingly, excess Rio1 results in accumulation of miscleaved rRNA. Ribosomes containing miscleaved rRNA can translate, albeit more slowly, thereby inviting collisions with trailing ribosomes. These collisions result in degradation of the defective ribosomes utilizing parts of the machinery for mRNA QC. Altogether, the data support a model in which Rio1 inspects the 3′-end of the nascent 18S rRNA to prevent miscleaved 18S rRNA-containing ribosomes from erroneously engaging in translation, where they induce ribosome collisions. The data also demonstrate how ribosome collisions purify cells of altered ribosomes with different functionalities, with important implications for the concept of ribosome heterogeneity.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141195096","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":"Cas9 degradation in human cells using phage anti-CRISPR proteins","authors":"Zuriah Meacham, Luisa Arake de Tacca, Joseph Bondy-Denomy, David Rabuka, Michael Schelle","doi":"10.1371/journal.pbio.3002431","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002431","url":null,"abstract":"Bacteriophages encode anti-CRISPR (Acr) proteins that inactivate CRISPR-Cas bacterial immune systems, allowing successful invasion, replication, and prophage integration. Acr proteins inhibit CRISPR-Cas systems using a wide variety of mechanisms. AcrIIA1 is encoded by numerous phages and plasmids, binds specifically to the Cas9 HNH domain, and was the first Acr discovered to inhibit SpyCas9. Here, we report the observation of AcrIIA1-induced degradation of SpyCas9 and SauCas9 in human cell culture, the first example of Acr-induced degradation of CRISPR-Cas nucleases in human cells. AcrIIA1-induced degradation of SpyCas9 is abolished by mutations in AcrIIA1 that break a direct physical interaction between the 2 proteins. Targeted Cas9 protein degradation by AcrIIA1 could modulate Cas9 nuclease activity in human therapies. The small size and specificity of AcrIIA1 could be used in a CRISPR-Cas proteolysis-targeting chimera (PROTAC), providing a tool for developing safe and precise gene editing applications.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138586035","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":"Sensory processing in humans and mice fluctuates between external and internal modes","authors":"V. Weilnhammer, Heiner Stuke, K. Standvoss, Philipp Sterzer","doi":"10.1371/journal.pbio.3002410","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002410","url":null,"abstract":"Perception is known to cycle through periods of enhanced and reduced sensitivity to external information. Here, we asked whether such slow fluctuations arise as a noise-related epiphenomenon of limited processing capacity or, alternatively, represent a structured mechanism of perceptual inference. Using 2 large-scale datasets, we found that humans and mice alternate between externally and internally oriented modes of sensory analysis. During external mode, perception aligns more closely with the external sensory information, whereas internal mode is characterized by enhanced biases toward perceptual history. Computational modeling indicated that dynamic changes in mode are enabled by 2 interlinked factors: (i) the integration of subsequent inputs over time and (ii) slow antiphase oscillations in the perceptual impact of external sensory information versus internal predictions that are provided by perceptual history. We propose that between-mode fluctuations generate unambiguous error signals that enable optimal inference in volatile environments.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138586272","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":"Eukaryotic CD-NTase, STING, and viperin proteins evolved via domain shuffling, horizontal transfer, and ancient inheritance from prokaryotes","authors":"Edward M. Culbertson, T. C. Levin","doi":"10.1371/journal.pbio.3002436","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002436","url":null,"abstract":"Animals use a variety of cell-autonomous innate immune proteins to detect viral infections and prevent replication. Recent studies have discovered that a subset of mammalian antiviral proteins have homology to antiphage defense proteins in bacteria, implying that there are aspects of innate immunity that are shared across the Tree of Life. While the majority of these studies have focused on characterizing the diversity and biochemical functions of the bacterial proteins, the evolutionary relationships between animal and bacterial proteins are less clear. This ambiguity is partly due to the long evolutionary distances separating animal and bacterial proteins, which obscures their relationships. Here, we tackle this problem for 3 innate immune families (CD-NTases [including cGAS], STINGs, and viperins) by deeply sampling protein diversity across eukaryotes. We find that viperins and OAS family CD-NTases are ancient immune proteins, likely inherited since the earliest eukaryotes first arose. In contrast, we find other immune proteins that were acquired via at least 4 independent events of horizontal gene transfer (HGT) from bacteria. Two of these events allowed algae to acquire new bacterial viperins, while 2 more HGT events gave rise to distinct superfamilies of eukaryotic CD-NTases: the cGLR superfamily (containing cGAS) that has diversified via a series of animal-specific duplications and a previously undefined eSMODS superfamily, which more closely resembles bacterial CD-NTases. Finally, we found that cGAS and STING proteins have substantially different histories, with STING protein domains undergoing convergent domain shuffling in bacteria and eukaryotes. Overall, our findings paint a picture of eukaryotic innate immunity as highly dynamic, where eukaryotes build upon their ancient antiviral repertoires through the reuse of protein domains and by repeatedly sampling a rich reservoir of bacterial antiphage genes.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138588034","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":"Collective production of hydrogen sulfide gas enables budding yeast lacking MET17 to overcome their metabolic defect","authors":"Sonal, Alex E. Yuan, Xueqin Yang, Wenying Shou","doi":"10.1371/journal.pbio.3002439","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002439","url":null,"abstract":"Assimilation of sulfur is vital to all organisms. In S. cerevisiae, inorganic sulfate is first reduced to sulfide, which is then affixed to an organic carbon backbone by the Met17 enzyme. The resulting homocysteine can then be converted to all other essential organosulfurs such as methionine, cysteine, and glutathione. This pathway has been known for nearly half a century, and met17 mutants have long been classified as organosulfur auxotrophs, which are unable to grow on sulfate as their sole sulfur source. Surprisingly, we found that met17Δ could grow on sulfate, albeit only at sufficiently high cell densities. We show that the accumulation of hydrogen sulfide gas underpins this density-dependent growth of met17Δ on sulfate and that the locus YLL058W (HSU1) enables met17Δ cells to assimilate hydrogen sulfide. Hsu1 protein is induced during sulfur starvation and under exposure to high sulfide concentrations in wild-type cells, and the gene has a pleiotropic role in sulfur assimilation. In a mathematical model, the low efficiency of sulfide assimilation in met17Δ can explain the observed density-dependent growth of met17Δ on sulfate. Thus, having uncovered and explained the paradoxical growth of a commonly used “auxotroph,” our findings may impact the design of future studies in yeast genetics, metabolism, and volatile-mediated microbial interactions.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138592223","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":"Changes in sea floor productivity are crucial to understanding the impact of climate change in temperate coastal ecosystems according to a new size-based model","authors":"A. Audzijonyte, Gustav W. Delius, R. Stuart‐Smith, C. Novaglio, G. Edgar, Neville S. Barrett, Julia L. Blanchard","doi":"10.1371/journal.pbio.3002392","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002392","url":null,"abstract":"The multifaceted effects of climate change on physical and biogeochemical processes are rapidly altering marine ecosystems but often are considered in isolation, leaving our understanding of interactions between these drivers of ecosystem change relatively poor. This is particularly true for shallow coastal ecosystems, which are fuelled by a combination of distinct pelagic and benthic energy pathways that may respond to climate change in fundamentally distinct ways. The fish production supported by these systems is likely to be impacted by climate change differently to those of offshore and shelf ecosystems, which have relatively simpler food webs and mostly lack benthic primary production sources. We developed a novel, multispecies size spectrum model for shallow coastal reefs, specifically designed to simulate potential interactive outcomes of changing benthic and pelagic energy inputs and temperatures and calculate the relative importance of these variables for the fish community. Our model, calibrated using field data from an extensive temperate reef monitoring program, predicts that changes in resource levels will have much stronger impacts on fish biomass and yields than changes driven by physiological responses to temperature. Under increased plankton abundance, species in all fish trophic groups were predicted to increase in biomass, average size, and yields. By contrast, changes in benthic resources produced variable responses across fish trophic groups. Increased benthic resources led to increasing benthivorous and piscivorous fish biomasses, yields, and mean body sizes, but biomass decreases among herbivore and planktivore species. When resource changes were combined with warming seas, physiological responses generally decreased species’ biomass and yields. Our results suggest that understanding changes in benthic production and its implications for coastal fisheries should be a priority research area. Our modified size spectrum model provides a framework for further study of benthic and pelagic energy pathways that can be easily adapted to other ecosystems.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138616183","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}