Genetics最新文献

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.

Genomic mating uses genome-wide information to design crosses that maximize genetic gain while managing diversity. Expected gain is often predicted through the usefulness criterion, which depends on family means and variances. However, existing equations mix incompatible parameterizations when considering dominance effects. Furthermore, diversity control is often tuned with metrics that lack a direct link to the loss of additive variation and long-term gain. We derived equations that compute family mean and within-family variance consistently under breeding and genotypic parameterizations by computing locus-specific values using genotypic frequencies and propagating them to the entire genome through linkage disequilibrium covariances. We also developed a diversity metric that estimates the proportion of additive standard deviation lost and integrated both advances into the MateR software. We evaluated performance in simulated diploid and autotetraploid crop populations across multiple breeding schemes and against existing tools. The new equations predicted family means and variances with near-perfect accuracy when true QTL effects were known. With estimated marker effects, correlations were roughly 0.55-0.90 for family mean and about 0.25 for within-family standard deviation. The diversity metric matched the expected loss of additive standard deviation under random sampling and tracked loss of genic variance under selection. This framework unifies prediction of cross usefulness under dominance and supplies an interpretable diversity control directly tied to long-term gain. Implemented in MateR, it applies to diploids and autopolyploids and accommodates common breeding program constraints, including hybrid schemes and testers.

The nuclear pore complex (NPC) is a major component of the nuclear envelope (NE), which mediates nucleocytoplasmic transport and is involved in a variety of transport-independent processes, including genome organization and cell division. In plants, several NPC subunits are species-specific, and their roles in meiosis remain poorly understood. Here, we characterize the function of the plant-specific nuclear basket nucleoporin NUP1/NUP136 during meiosis in Arabidopsis thaliana. Loss of NUP136 leads to a marked reduction in chiasma frequency, resulting in univalents, and the persistence of chromosome interlocks at metaphase I. This phenotype is consistent with defects in early chromosome interactions and crossover (CO) formation, as evidenced by a reduced number of MLH1 foci. In the mutant there is also an altered spatial distribution of centromeres, telomeres, and nucleolar organizing regions (NORs), pointing to changes in the dynamics of these chromosomal domains during meiotic prophase I. Meiotic defects in nup136-2 mutants are modestly aggravated by the loss of the related paralog NUP82. Our results demonstrate that NUP1/NUP136 is important for proper homologous chromosome pairing and for ensuring the formation of the obligatory CO, likely by contributing to NE organization and facilitating the chromosomal contacts that support recombination during prophase I.

The proper coordination of transcription factors, ATP dependent chromatin remodelers and histone modifications is essential for tissue specific gene expression, but how gene expression is regulated at these different levels is not well understood. In C. elegans, H3K4 methylation that is acquired in the germline is reprorgammed at fertilization by the H3K4me1/2 demethlyase SPR-5/LSD1/KDM1A and the H3K9 methyltransferase MET-2/SETDB1/KMT2E. SPR-5/MET-2 maternal reprogramming is required to help establish the germline-soma distinction and prevent developmental delay by preventing inherited H3K4 methylation from inappropriately maintaining germline gene expression in somatic tissues. To determine if the DREAM transcriptional repressor complex and the MEC NuRD ATP dependent nucleosome remodeling and histone deacetylase complex function to reinforce SPR-5/MET-2 maternal reprogamming, we asked if loss of these complexes affects the ectopic germline transcription and developmental delay in spr-5; met-2 double mutants. We find that knocking down the DREAM or MEC NuRD complexes specifically exacerbates the developmental delay and the ectopic expression of germline genes in the soma caused by loss of SPR-5 and MET-2. In addition, the DREAM and MEC NuRD complexes bind together at SPR-5/MET-2 reprogramming targets. These data suggest that the transcriptional repression of DREAM and the ATP dependent chromatin remodeling and deactylation activities of the MEC NuRD complex are required somatically to reinforce maternal histone reporgamming by SPR-5/MET-2. Thus, these data provide a novel example of how gene regulation is coordinated at multiple levels to maintain the germline-soma distinction and ensure proper development.