Genetics最新文献

The Caenorhabditis Genetics Center is launching a new website feature-"Curated Special Collections"-designed to help researchers navigate the ever-evolving lists of strains harboring specialized genetic tools. Each collection will be assembled by experts who provide an overview of the system and curate the strains and their associated information as the collection expands. A companion review article will provide an in-depth analysis of each tool collection, including comparisons of different methods and modifications, discussion of their advantages and limitations, and practical guidance for getting started. The first collection in this series, Protein Degradation Systems, focuses on 2 protein depletion methods: (i) the auxin-inducible and (ii) ZIF-1/ZF1 degradation systems. Both methods are increasingly popular in Caenorhabditis elegans research because they allow rapid and precise temporal and spatial control over protein depletion. The inaugural collection and this companion review, together with additional collections forthcoming, will help researchers identify the most suitable approaches and strains for their experiments. Importantly, these collections will also lower the barrier for investigators primarily working in other model organisms to gain entry to the worm as a system for testing their ideas.

Meiotic drive is a phenomenon that violates Mendel's Law of Equal Segregation, leading to biased transmission of the meiotic driver to the offspring. D. melanogaster Stellate (Ste) is an X-linked meiotic driver that preferentially harms Y-chromosome-bearing spermatids, thereby favoring the transmission of the X chromosome to the next generation. We have recently shown that Ste protein segregates asymmetrically during meiosis I with a strong bias toward the Y-chromosome-inheriting side, leading to the eventual demise of the Y-chromosome-containing spermatids. However, the cellular mechanisms by which Ste protein interferes with spermatid development remain unknown. Here, we show that Ste-containing spermatids are delayed in the process of nuclear envelope remodeling, an essential process during sperm DNA compaction. We show that components of the nuclear lamina (such as Lamin Dm0, and the LEM domain proteins Otefin and Bocks) are rapidly removed during nuclear envelope remodeling during the early stages of normal spermatid development. However, Ste-containing spermatids retained these nuclear lamina proteins for a prolonged time. Their delayed removal is associated with defective formation of the dense complex, which is composed of a bundle of microtubules and serves as a structural support for sperm nuclear morphogenesis. Defective dense complex formation in Ste-containing spermatids led to defective sperm DNA compaction. Together, the present study reveals an unexpected cellular mechanism by which a meiotic driver, Ste, sabotages sperm development.

Here, we describe a collection of genomic database portals, SoyBase (https://soybase.org), Legume Information System (https://legumeinfo.org), and PeanutBase (https://peanutbase.org), that support breeding and research work in the legume plant family. The legume family includes important crops such as soybean, peanut, common bean, lentils, chickpeas, as well as approximately 20,000 other species that are important in all terrestrial ecosystems. Beyond the value of the portals for species in this large clade (as well as for plant biology more generally), the database and site architecture of these portals will be of interest to developers of similar genomic sites, as the data management and software solutions are generic and should be applicable to a wide variety of organisms. The architecture for these sites has been designed for rapid, modular, flexible development well suited to genomic data and to rapid incorporation of new data. Website content is handled with a static site generator (Jekyll). Interactive applications are developed using javascript encapsulated as Web Components that access back-end data via APIs for stability and flexibility. This architecture allows for both code portability and for customization to serve the unique needs of each research community.

Multiple tissue stem cells depend on glycolysis or β-oxidation for cell fate decisions. However, how universal these requirements are and how they change as stem cell daughters undergo differentiation remains unclear. The Drosophila ovary is a powerful stem cell model with two distinct stem cell populations: germline stem cells (GSCs), which produce oocytes to perpetuate the species, and follicle stem cells (FSCs), a somatic lineage. Several studies have begun addressing the roles of metabolism within the Drosophila female GSC lineage, but direct systematic analyses of glycolysis and/or mitochondrial fatty acid β-oxidation requirements across these lineages have been lacking. Here, using genetic mosaic analysis with null alleles, we found that genes encoding key regulatory glycolytic enzymes-Phosphofructokinase (Pfk) and Pyruvate kinase (Pyk)-are not cell autonomously required for GSC maintenance, proliferation, or early differentiation through 16-cell germline cyst formation and oocyte specification. Although germline cysts lacking Pfk or Pyk function can develop through early vitellogenesis, they grow slowly and display impaired nurse cell chromatin dispersal. By contrast, FSCs and their early daughters require Pfk (but not Pyk) for normal survival, while later follicle cells need both Pfk and Pyk for survival and only Pfk for proliferation, suggesting that follicle cells predominantly require glycolytic intermediates upstream of Pyk. Surprisingly, mitochondrial β-oxidation was dispensable in both lineages. These findings uncover an unusual metabolic state in GSCs and their early daughters, with marked differences from the neighboring FSC lineage and other somatic stem cells.

C. elegans is a powerful model for dissecting biological processes in vivo. In particular, the ease of generating targeted knock-in alleles makes it possible to visualize and functionally modify endogenous proteins to gain fundamental insights into biological mechanisms. Methods for C. elegans genome engineering typically utilize selectable markers, visual screening for fluorescence, or PCR genotyping to identify successfully edited animals. A common genetic tool known as the Self-Excising Cassette (SEC) combines drug and phenotypic selection, which makes it possible to screen large numbers of progeny rapidly and with minimal hands-on effort. However, N-terminal and internal knock-ins using the SEC cause loss of function until the selectable marker cassette is excised, which makes it impossible to isolate homozygous lines for essential genes prior to SEC excision. To simplify generating knock-ins for essential genes, we developed a Nested, Self-Excising selection Cassette (NSEC) that is located entirely within a synthetic intron and does not interfere with the expression of endogenously tagged NSEC-fusion proteins. This innovation makes it possible to isolate homozygous lines for N-terminally and internally tagged genes prior to selectable marker excision while preserving endogenous protein function. This method allows for a standardized workflow to generate N-terminal and internal tags in any background and without the need for genetic balancers. We designed versions of NSEC that include an optional auxin-inducible degron tag and mTurquoise2, GFP, mStayGold, mNeonGreen, or mScarlet-I fluorescent proteins for experimental flexibility. The NSEC expands our molecular toolbox and enhances the scalability, efficiency, and versatility of C. elegans genome engineering.

CottonGen (https://www.cottongen.org) serves as an integrated genomics platform for the cotton research community, combining comprehensive data storage with sophisticated analysis tools built on the Tripal framework. Since its establishment in 2012, CottonGen has consolidated and expanded resources previously scattered across CottonDB and the Cotton Marker Database while developing advanced analytical capabilities. The platform has expanded substantially between 2021 and 2025, with tetraploid genome assemblies and gene annotations increasing 3-fold, genotype datasets doubling, and phenotype records growing 1.8-fold. Recent developments include enhanced search and visualization capabilities through updated Map Viewer and Breeding Information Management System tools, integration of genome-wide association studies and gene expression analysis via new Tripal modules, and implementation of Genotype Investigator for Genome-Wide Analyses for interactive large-scale genotyping data exploration. Beyond data storage, CottonGen provides integrated analysis workflows spanning sequence similarity searches, synteny analysis, expression profiling, marker-trait association studies, and breeding data management. These capabilities support diverse research applications from comparative genomics and gene discovery to marker-assisted selection and cultivar development. As the official platform for the International Cotton Genome Initiative, CottonGen helps coordinate global cotton research efforts and maintains a comprehensive, actively curated resource that evolves with community research priorities.

The conserved Ess1 prolyl isomerase (PIN1 in human) binds the carboxy-terminal domain (CTD) of RNA Pol II, and plays multiple roles in transcription regulation. Consistent with an essential role of the human PIN1 in telomere maintenance, previous screenings have identified the yeast Ess1 as a telomere length maintenance gene. Here, we provide evidence that Ess1 is involved in regulating both telomere transcription and replication. We find that depletion of Ess1 leads to a failure in transcription termination, explaining the essential role of Ess1 in maintaining a low level of telomere repeat containing RNA (TERRA). Furthermore, we show that Ess1 depletion promotes telomere shortening and accelerates senescence in telomerase-deficient cells. Notably, the depletion of Ess1 causes synthetic growth defects and telomere shortening in mre11Δ cells, and compromises rif2Δ-induced telomere elongation. Additionally, Ess1 depletion also accelerates senescence and eliminates type II telomere recombination in rad50Δ tlc1Δ cells. Lastly, Ess1 depletion decreases the accumulation of single-stranded DNA at telomere ends. These results support the model that Ess1 positively regulates both telomerase- and recombination-dependent telomere replication by promoting telomere-end resection. Taken together, this study reveals the yeast Ess1 as a new regulator of telomere transcription and replication via a distinct mechanism from the human PIN1.

In male heterogametic species, the difference in ploidy of the X chromosome between females (XX) and males (XY) has led to the evolution of sex chromosome-specific regulatory mechanisms. In Drosophila melanogaster, expression of the single X chromosome is upregulated in male somatic cells by the well-known process of dosage compensation. In contrast, expression of the X chromosome in the male germline is suppressed by an as yet unknown mechanism that has similarities to mammalian meiotic sex chromosome inactivation. To gain insight into this suppression, we carried out a forward mutagenesis screen for males exhibiting increased expression of a testis-specific, X-linked reporter gene. Two independent mutants were recovered that showed global upregulation of the X chromosome in the male germline and male-specific sterility. Expression of the gene-poor Y chromosome was also upregulated in the mutants. Despite the use of chemical mutagenesis to induce point mutations, both mutants were found to have large, reciprocal translocations between the X chromosome and chromosome arm 3R. Genes on the translocated regions of the X chromosome, encompassing approximately 20 Mb, showed uniform upregulation in testis, which is consistent with a regulatory interaction between the centromeric heterochromatin and the euchromatin. Our observations lend support to classical genetic studies that posited the functional significance of X chromosome suppression in the male germline and its link to male fertility.

Centralizing valuable community data and resources into a user-friendly interface and accessible repository has become essential for agricultural science; embracing Findable Accessible, Interoperable, and Reusable (FAIR) principles is now standard for effective databases. SorghumBase (https://www.sorghumbase.org) is a knowledgebase designed for the sorghum research community. The SorghumBase team curates genomic, transcriptomic, variation, and phenotypic information and aggregates community events, providing rich visualizations and bulk data access. The modular framework of the database is built with open-access software to yield a robust, modifiable, and sustainable data infrastructure. Release 9 of SorghumBase includes: (i) 88 sorghum reference genomes and an updated pan-gene index, (ii) over 100 million variants have been mapped onto the 2 genomes, BTx623 and Tx2783, (iii) assignment of 41 million Reference Cluster SNP identifiers (rsIDs) from BTx623 across the pan-genome, (iv) updated gene search homology, gene expression, and germplasm visualizations and features, (v) added and standardized 234 phenotypic data from 40 community-generated GWAS studies and 148 traits from the Sorghum QTL Atlas (Oz Sorghum), (vi) improved news, funding, and a research content management system for community access and interaction, (vii) outreach materials including training documents and videos, and (viii) community engagement initiatives through training and working groups. SorghumBase serves as a hub for sorghum data and stakeholder engagement while promoting community standards to drive research and multi-omics breeding approaches.

Cytoplasmic aggregation of nuclear proteins such as TDP-43 (TAR DNA-binding protein 43) and FUS (fused in sarcoma) is associated with several neurodegenerative diseases. Studies in higher cells suggest that aggregates of TDP-43 and FUS sequester polysomes by binding RACK1 (receptor for activated C kinase 1), a ribosomal protein, thereby inhibiting global translation and contributing to toxicity. However, RACK1 is also a scaffold protein with a role in many other cellular processes including autophagy. Using yeast, we find that deletion of the RACK1 ortholog, ribosomal protein ASC1, reduces TDP-43 toxicity, but not FUS toxicity. TDP-43 foci remain liquid like in the absence of ASC1 but they become smaller. This is consistent with findings in mammalian cells. However, using double label fluorescent tags and co-immunoprecipitation we establish that ASC1 does not co-localize with TDP-43 foci, challenging the polysome sequestration hypothesis. Instead, ASC1 appears to influence toxicity through regulation of autophagy. We previously showed that TDP-43 expression inhibits autophagy and TOROID (TORC1 Organized in Inhibited Domains) formation and that genetic modifiers that rescue yeast from TDP-43 toxicity reverse these effects. Here we show that FUS does not inhibit autophagy. Deletion of ASC1 enhances a non-canonical form of autophagy that effectively counteracts TDP-43 induced autophagy inhibition despite reduced TOROID formation. Our findings highlight autophagy-not polysome sequestration-as a key mechanism underlying ASC1-mediated modulation of TDP-43 toxicity and suggest autophagy as a promising therapeutic target.