PLOS Genetics: New Articles

Recurrent evolution of cryptic triploids in cultivated enset increases yield

2026-07-24T14:00:00Z

by Yann Dussert, James S. Borrell, Jonathan Stocks, Harriet V. Hunt, Oliver W. White, Paul Wilkin, Richard Buggs, Lucie Büchi, Sebsebe Demissew, Feleke Woldeyes, Ilia J. Leitch, Wendawek M. Abebe, Richard A. Nichols

The high incidence of polyploidy in crops could be explained if domestication involved the selection of polyploids (cytotypes with more than two sets of chromosomes). Ancestral horticulture could have targeted desirable traits including yield, robustness to stress or disease, rather than requiring knowledge of polyploidy itself. We find evidence for this process underway in enset (Ensete ventricosum, Musaceae), a highly resilient crop constituting the main staple for over 20 million people in Ethiopia, which is clonally propagated and cultivated for its starch-rich corm and pseudostem. Prior to this study, enset was thought to be exclusively diploid (2n = 2x = 18). Using a newly-assembled chromosome-scale reference genome, and sequence data from 723 wild and domesticated enset individuals from southwestern Ethiopia, we demonstrate that around 20% of cultivated enset clones are triploid. We show that triploidy has arisen multiple times independently, that the triploid lineages have been given distinct landrace names, and planted disproportionately frequently. Enset triploid clones also have a higher pseudostem volume than diploids on average. As well as providing evidence for enduring selection on triploids, our results reveal valuable genetic diversity captured by these triploid lines. They represent key resources for scientifically directed breeding of this major crop in the Ethiopian agrosystem, and could improve food security in Sub-Saharan Africa.

Partitioning of the truncated insulin receptor DAF-2B between homodimers and heterodimers influences insulin signaling in C. elegans

2026-07-23T14:00:00Z

by Bryan A. Martinez, Anne M. Stene, Jonathan I. Hauser, Karla J. Opperman, Jonathan N. Sachs, Anthony R. Braun, Matthew S. Gill

Insulin / insulin-like growth factor signaling (IIS) in C. elegans is mediated by the DAF-2 receptor and insulin-like peptides (ILP) that can act as agonists or antagonists. DAF-2 signaling is also affected by DAF-2B, a truncated, non-signaling, secreted isoform of DAF-2 that acts as a decoy receptor by sequestering ILPs. In this study, we performed a forward genetic screen for modifiers of DAF-2B protein expression and identified a mutation in unc-31 that increased DAF-2B. UNC-31 is involved in dense core vesicle docking and is required for neuropeptide secretion, including ILPs. As a result, unc-31 mutants constitutively enter the dauer larval stage and are long-lived due to reduced IIS. We find that increased nervous system DAF-2B accumulation is associated with reduced agonist ILP availability, in both unc-31 mutants and wild type worms. Using auxin-induced degradation (AID) and fluorescence lifetime imaging microscopy-Förster resonance energy transfer (FLIM-FRET), we find that a significant fraction of nervous system DAF-2B is in the form of a heterodimeric complex with a full-length DAF-2 receptor isoform, representing a new class of DAF-2 hybrid receptor. In unc-31 mutants, DAF-2B also undergoes endocytosis in neurons in an AP2-dependent manner and genetic manipulation of daf-2b in the unc-31 mutant suggests that DAF-2B homodimers may function to reinforce a reduced insulin signaling state by clearing agonist ILPs from the extracellular space. These findings indicate that DAF-2B not only forms homodimers, but also hybrid receptors with full-length DAF-2, to regulate the activity of the large and diverse family of ILPs in C. elegans.

Photoperiodic patterns in miRNA-mRNA pairs and tRNA fragments revealed by time-course co-sequencing in Arabidopsis

2026-07-22T14:00:00Z

by Chun Chung Leung, Daniel A. Tarté, Joshua M. Gendron

In plants, the response to photoperiod is marked by global reprogramming of gene expression that drives extensive developmental changes. Small RNAs (sRNAs) play important roles in this process, but a comprehensive characterization of micro RNAs (miRNAs) and the more recently recognized transfer RNA fragments (tRFs) within this context is lacking. Herein, we characterize the patterns of miRNAs and tRFs in Arabidopsis by performing time-course sRNA-sequencing across three photoperiods. By comparing with our previous messenger RNA (mRNA) sequencing time-courses, we identified positively- or inversely-correlated miRNA-mRNA pairs between the two co-sequenced datasets that suggest photoperiodic sRNA regulations. Furthermore, we revealed 20 patterns of photoperiodic tRFs. These patterns are linked to the transfer RNA (tRNA) isotypes and positions they derive from, suggesting that tRFs are subjected to photoperiodic regulation. Finally, we present a major update to our web-app “Photo-Graph,” (http://gendron-lab.shinyapps.io/PhotoGraph) featuring new visualizations of this mRNA-sRNA co-sequencing dataset. In summary, our findings indicate that plants regulate sRNAs within a diel cycle in a photoperiodic manner and form highly-correlated pairs with mRNAs.

Multi-ancestry colocalization approaches

2026-07-21T14:00:00Z

by Cathy Shen, Josée Dupuis, Qihuang Zhang

Genome-wide association studies (GWAS) have identified thousands of variants associated with complex traits, but many are non-causal. Statistical fine-mapping methods aim to pinpoint the most likely causal variants among the many associated ones. While most fine-mapping methods were originally limited to single ancestry analysis, multi-ancestry fine-mapping methods are now available, leveraging differences in linkage disequilibrium (LD) and minor allele frequencies (MAFs) across ancestries to improve fine-mapping resolution. However, the biological relevance of the putative causal variants identified through fine-mapping often remains unclear. Colocalization methods improve interpretability by integrating GWAS data with other functional genomics datasets to assess whether two traits share the same causal variants. Despite the growing availability of multi-ancestry data, there are currently no established methods for multi-ancestry colocalization. In this study, we propose multi-ancestry colocalization approaches through the integration of multi-ancestry fine-mapping methods, SuSiEx and MsCAVIAR, with single ancestry colocalization methods, coloc and eCAVIAR. We introduce coloc_SuSiEx, eCAVIAR_SuSiEx, eMsCAVIAR and coloc_MsCAVIAR. The performance of the proposed approaches is evaluated and compared through simulation studies. In loci with a single causal variant, credible set sizes across the four approaches were comparable, as was the prioritization of the true causal variant. MsCAVIAR-based approaches were more computationally expensive compared to SuSiEx-based approaches, which is an important consideration for the analysis of regions with multiple causal variants. Compared to the coloc-based approaches, the eCAVIAR-based approaches tended to report lower loci level colocalization posterior probabilities. For the analysis of loci with multiple causal variants, coloc_SuSiEx is the preferred approach. We apply the proposed approaches to perform a colocalization analysis of multi-ancestry T2D GWAS data from the DIAMANTE Consortium and European pQTL data from the INTERVAL study. This work addresses the increasing need for multi-ancestry approaches to colocalization analysis as more multi-ancestry data become available.

Cross-family and phage-specific gene requirements for Klebsiella infection revealed by scalable RB-TnSeq genetic screens

2026-07-20T14:00:00Z

by Marissa R. Gittrich, Courtney M. Sanderson, Cara M. Noel, Erica Babusci, Sumeyra C. Selbes, Madeline Svab, Isabella Murray, Collis Bousliman, Ami Fofana, Aghiad Daboul, Jonathan Leopold, Alessandra Gonçalves de Melo, Marion Urvoy, Sylvain Moineau, Vivek K. Mutalik, Matthew B. Sullivan

Bacteriophages are being cataloged at an accelerating pace and are recognized as key players in nutrient and energy cycling across ecosystems. Yet the bacterial genetic determinants that govern phage-host specificity and infection success remain poorly understood, particularly in clinically and ecologically important genera such as Klebsiella where prior receptor characterization has been almost entirely limited to capsulated strains. Here we used a randomly barcoded, genome-wide, loss-of-function transposon mutant library (RB-TnSeq) of Klebsiella sp. M5al, a naturally acapsular, nitrogen-fixing rhizobacterium, to generate the first systematic, cross-family map of phage receptor gene dependencies in Klebsiella. Challenging the library against 25 double-stranded DNA phages spanning five families in 213 parallel assays, we identified 42 bacterial genes associated with phage infection, of which 15 had no prior association with phage infection in any bacterial system. Disruption of surface receptor biosynthesis genes conferred cross-resistance across multiple phage families, while intracellular gene disruptions had predominantly phage-specific effects. Clonal validation of eight genes confirmed LPS outer core biosynthesis genes as primary receptor determinants alongside additional host factors spanning outer membrane transport, cofactor biosynthesis, and two-component signaling. Comparative analysis across all 25 phages revealed that phage genus rather than family is the stronger predictor of host gene dependency profiles, a finding with direct implications for the functional annotation of uncharacterized phage isolates and rational phage cocktail design. Together, these findings provide a community resource for linking phage genomic diversity to functional host interaction space in this ecologically and clinically important genus.

A tumor-suppressive role of the PRC1 Polycomb epigenetic complex in the maintenance of adult Drosophila intestinal stem cell identity

2026-07-17T14:00:00Z

by Aurélia Joly, Ana-Maria Popmihaylova, Corinne Rancurel, Julie Soltys, Rihab Loudhaief, Armel Gallet, Edan Foley, Anne-Marie Martinez, Raphaël Rousset

Chromatin modulators, like Polycomb group proteins, are key epigenetic regulators of gene expression and are frequently mutated in cancers. In adult stem cells, epigenetic regulation maintains their identity and controls their differentiation during homeostasis or aging, but its direct role in tumorigenesis remains unclear. Here we developed a novel tumor model in Drosophila by exploring the function of Polycomb Repressive Complex 1 (PRC1) in adult intestinal stem cells (ISCs). Disrupting core PRC1 components in ISCs induces the formation of small cell clusters devoid of intestinal markers, a novel phenotype linked to premature mortality under stress. These clusters exhibit neoplastic characteristics such as overproliferation and continuous growth in serial transplantations, leading to their designation as tumor-initiating intestinal cells (TIICs). While JAK/STAT signaling contributes to TIIC growth, the NF-κB-related Toll/Imd immune pathways restrict their expansion independently of cell death. Altogether, our results highlight PRC1 as an epigenetic tumor suppressor in adult stem cells.

Identifying severe COVID-19 risk variants modulating enhancer reporter activity in lung cells

2026-07-17T14:00:00Z

by Giovanna Weykopf, Wendy A. Bickmore, Simon C. Biddie, Elias T. Friman

Common genetic variants contribute to risk for complex human diseases. However, despite thousands of associations, variants modulating disease risk and their functional impact remain largely unknown. This includes SARS-CoV-2 infection, where outcomes range from asymptomatic to fatal. Most genetic risk variants associated with COVID-19 disease, identified through genome wide association studies, are located in the non-coding genome and may function by altering gene expression in disease-relevant cells and tissues. To address this at scale, we tested >4800 severe COVID-19-associated variants to determine the impact of individual variants and variant combinations on regulatory activity using Self-Transcribing Active Regulatory Region sequencing, a massively-parallel reporter assay. Focusing on variants that may have their impact in the lung, in a lung epithelial cell line (A549) we identify 166 variants within active sequences, of which 29 modulate activity allele-specifically. Evaluating variant combinations, we observe both additive and non-additive effects on regulatory activity. We employ state-of-the-art deep learning models to interpret allele-specific variant effects on regulatory activity and endogenous genomic features. Our work provides a set of prioritised severe COVID-19-associated variants that modulate regulatory activity in lung epithelial cells, candidate transcription factors, and candidate target genes with potential to be disease modifying.

Contrasting evolutionary patterns of helper and sensor NRC NLRs in lettuce reflect functional divergence following subfunctionalization

2026-07-16T14:00:00Z

by Hsuan Pai, Toshiyuki Sakai, Andres Posbeyikian, Raoul Frijters, Yu Sugihara, Mauricio P. Contreras, Jiorgos Kourelis, Hiroaki Adachi, Sophien Kamoun, AmirAli Toghani

Nucleotide-binding domain and leucine-rich repeat immune receptors (NLRs) are known for their rapid evolution, even at the intraspecific level, yet the rates of evolution differ significantly across NLRs. However, the degree to which evolutionary patterns reflect functional divergence remains poorly understood, notably in important crop species. Within the NRC (NLR Required for Cell Death) network in Asterids, sensor NLRs detect pathogen presence but require NRC helpers for signaling and to confer immunity. We conducted a comparative analysis of NLRs across 40 Solanales and 29 Asterales genomes to explore NRC network expansion and diversification within the less-studied Asterales order. Our findings reveal that the NRC network has expanded less in Asterales compared to Solanales. We functionally validated an Asterales NRC network with 2 helpers and 9 sensors in common lettuce (Lactuca sativa). Through selection analysis and structural modeling of NRC gene family in the Lactuca genus, we found distinct evolutionary trajectories between NRC helpers and sensors. Sensors reliant on the phylogenetically conserved helper NRC0 experience limited diversification, whereas sensors dependent on other NRC helpers show higher rates of positive selection and gene duplication. Our results highlight the lineage- and function-specific evolution of the NRC network, offering insights into the evolutionary pressures shaping plant immune receptor networks.

Wiz regulates clustered protocadherin genes by restricting CTCF/cohesin loop extrusion in a genomic-distance biased manner

2026-07-16T14:00:00Z

by Tianjie Li, Jingwei Li, Leyang Wang, Haiyan Huang, Qiang Wu

Zinc finger proteins (ZFPs or ZNFs) constitute the largest family of transcription factors in mammals; however, their regulatory mechanism remains largely elusive. Here we propose COP (C2H2-ZFP occupancy predictor), a deep learning-based heuristic screening tool that integrates DNA sequence with protein primary and secondary features to assess ZFP genomic enrichments. Applying COP to the mouse clustered protocadherin (cPcdh) gene locus, we identified dozens of C2H2-ZFPs potentially involved in CTCF-mediated gene regulation with Wiz (widely interspaced zinc finger-containing protein) having the highest number of 12 ZFs. We confirmed Wiz enrichments at all of the CTCF-binding site (CBS) elements across the three Pcdh clusters by Myc-tagging the endogenous Wiz gene. Genetic experiments revealed significant increases of expression levels of the cPcdh genes upon Wiz deletion in both neuronal cells in vitro and in mouse brain in vivo. Finally, integrated ChIP-seq, RNA-seq, and 4C-seq analyses demonstrated that Wiz regulates CTCF/cohesin occupancy and long-range enhancer-promoter contacts in a genomic-distance biased manner. Together, these findings reveal a key role for Wiz in coupling cohesin occupancy to long-range cPcdh regulation and highlight important functions of C2H2-ZFPs in enhancer-promoter interactions.

Apical spectrin organizes cortical actin filament bundles to pattern C. elegans cuticle ridges

2026-07-16T14:00:00Z

by Prioty Ferheen Sarwar, Trevor James Barker, Ken Nguyen, Fung-Yi Chan, David H. Hall, Ana Xavier Carvalho, Meera Vedavalli Sundaram

The apical extracellular matrix can form elaborate three-dimensional structures on animal surfaces. To better understand the mechanisms that pattern and shape these structures, we focus on development of collagen-rich cuticle ridges (alae) in adult C. elegans. Previous studies suggested that longitudinal actin filament bundles (AFBs) in the lateral seam epidermis specify alae position through a mechanism that involves post-secretory matrix delamination. Here we identify additional components of this highly organized cortical actin network and show that loss of the apical βH-spectrin SMA-1 specifically disrupts organization of the two AFBs that would normally flank the site where the middle alae ridge forms. Correspondingly, sma-1 loss, or mutation of its actin binding domains, also disrupts formation of the middle alae ridge. Ultrastructurally, sma-1 mutants have expanded regions of matrix delamination that can explain middle ridge loss. Together, these data highlight the importance of apical spectrin for organizing a patterned actin network within epithelia and show that, via its effects on actin organization, spectrin can also change the extracellular matrix and its patterns on animal surfaces.

A genomic-led strategy to anticipate drug safety effects

2026-07-16T14:00:00Z

by Brian R. Ferolito, Andrea R. V. R. Horimoto, Kai Gravel-Pucillo, Daniel J. Golden, Hesam Dashti, Claudia Giambartolomei, Danielle Rasooly, Rachael Matty, Liam Gaziano, Yakov Tsepilov, Lauren Costa, Nicole Kosik, Harris Ioannidis, Mohd Karim, Giovanna Winicki, Fiona Hunter, Claudia Langenberg, John C. Whittaker, Million Veteran Program , Tianxi Cai, Gina M. Peloso, Barbara Zdrazil, Maya Ghoussaini, Andrew R. Leach, Sumitra Muralidhar, Ines A. Smit, Juan P. Casas, J. Michael Gaziano, Kelly Cho, Alexandre C. Pereira

Safety-related issues account for approximately 25% of failures in new drug discovery programs. On top of that, many are discovered during post-marketing surveillance, significantly limiting drug utility and application. To proactively address these concerns, we developed a genetics-led strategy leveraging Mendelian Randomization (MR) across large-scale genetic datasets from the Million Veteran Program, FinnGen, and UK Biobank. By mapping genetic variants associated with gene expression and protein abundance to 1,449 harmonized human phenotypes, we systematically identified potential adverse drug reactions (ADR). Our extensive MR analysis, encompassing 16,915 protein-coding genes, demonstrated the capacity to predict hundreds of known ADR for approved medications, with approximately 40% corroborated by FDA Adverse Event Reporting System (FAERS) data. Additionally, we found significant enrichment of identified gene-mechanism pairs in clinical trials terminated early due to safety concerns, highlighting the clinical utility of genetics-informed safety prediction. Notably, immune-related pathways were prominently associated with ADR, indicating particular sensitivity within immune modulation targets. Our comprehensive atlas, integrating genetic evidence with pharmacological mechanisms, provides a robust predictive framework for anticipating drug safety, potentially enhancing decision-making in drug development and pharmacovigilance. An interactive web interface allowing filtering by gene, phenotype, drug phase, and mechanism of action is available at https://shiny.parse-health.org/safety/.

A generalized test of genotype–phenotype causality in population-sampled nuclear families

2026-07-15T14:00:00Z

by Yushi Tang, John D. Storey

We recently developed a causal inference framework and test—the Transmission Mean Test (TMT)—to identify causal genotype–phenotype relationships in population-sampled parent–child trios, where one child per family is observed. Here, we establish the generalized TMT (gTMT) for population-sampled nuclear families, allowing multiple offspring per family. This extension focuses on detecting genetic loci with non-zero average causal effects (ACE) on child phenotypes, taking into account that siblings share similar random family-specific effects. We construct a potential outcomes trait model that considers both individual-level and family-level heterogeneity, captures additive and non-additive genetic effects, and accommodates both quantitative (continuous or count) and dichotomous traits. We design an unbiased estimate dgTMT of the ACE and develop a sampling variance estimate σ^gTMT2 to form a statistic testing the null hypothesis of no causal effect. We provide both theory and empirical evidence demonstrating that gTMT is robust to confounding factors such as the population structure and family-specific effects. We analyze nuclear families in the UK Biobank as an illustrative example of the gTMT in action. When parental genotypes are missing, we propose to further extend gTMT by using Bayesian calculations on child genotypes to model parental genotypes as intermediate random variables.

An ancestral transmembrane transcription factor couples cell envelope regulation and the SOS response in Caulobacter crescentus

2026-07-15T14:00:00Z

by Kamilla Ankær Brejndal, Nikolaj Vestergaard Hansen, Koyel Ghosh, Sebastian Nielsen, Isabella Thorud, Lykke Haastrup Hansen, Lene Andrup Jakobsen, Martin Røssel Larsen, Clare Louise Kirkpatrick

The DNA damage (SOS) response in bacteria involves derepression of a set of genes in order to activate mechanisms to tolerate stress, repair DNA and slow down cell division. While some of these genes are well characterized, many genes exist which are clearly induced by DNA damage but for which the function is unclear. In Caulobacter crescentus, the toxin-antitoxin (TA) system higBA and a closely associated downstream transcription factor (higX) are strongly induced as part of the SOS response, but the role of higX is unknown. We show that, unexpectedly, HigX functions independently of HigBA as a cell membrane-associated regulator and is toxic when overexpressed in filamentous cells. ChIP-Seq indicated that it binds to several promoters associated with cell envelope regulation. In cells with the SOS response constitutively activated, HigX was overproduced, but at the same time was unable to bind the majority of its target promoters. higX was conserved among many alpha-proteobacteria, while higBA was only found upstream of it in a small number of Caulobacter genomes, including the universal laboratory strain C. crescentus NA1000. Compositional analysis suggested that higBA originated from a foreign source, while higX is likely ancestral to the alpha-proteobacteria. Our data support a model where dysregulation of HigX production and activity in filamentous cells contributes to cell envelope instability and antibiotic sensitivity. Thus, the protective effect of inhibiting cell division during the SOS response in order to repair the DNA, carries the hidden cost of interference with HigX-mediated cell envelope maintenance.

The B. subtilis translesion polymerase Pol Y1 is not strongly recruited to sites of replication upon different types of DNA damage

2026-07-14T14:00:00Z

by Sophia R. Martinez-Whitman, Chloe M. Santana, Alyssa P. Campbell, Denholm T. Feldman, Isaac E.Z. Jabaley, Luke G. O’Neal, McKayla E. Marrin, Elizabeth S. Thrall

One challenge to DNA replication is the presence of unrepaired damage on the template strand, which can stall the replication machinery. This stall can be resolved by the translesion synthesis (TLS) pathway, in which specialized translesion polymerases are recruited to copy damaged DNA. Because TLS polymerases are error-prone, their activity is regulated at multiple levels to minimize unnecessary mutagenesis. Although the molecular mechanisms of bacterial TLS have been extensively studied in Escherichia coli, less is known about this pathway in other species. In E. coli, the TLS polymerase Pol IV is minimally enriched at replication forks in the absence of DNA damage but is strongly recruited upon replication stalling, enabling TLS while minimizing mutagenesis. However, we recently showed that the Bacillus subtilis TLS polymerase Pol Y1, the homolog of Pol IV, is moderately enriched near replication sites even during normal growth and is not further enriched upon treatment with the DNA damaging agent 4-nitroquinoline 1-oxide (4-NQO). It is unknown whether this behavior is unique to 4-NQO or general to other types of DNA damage. In this study, we investigate the effects of four different DNA damaging agents (ultraviolet light, methyl methanesulfonate, nitrofurazone, and mitomycin C) in B. subtilis. We first characterize the contributions of the two TLS polymerases, Pol Y1 and Pol Y2, to DNA damage survival and damage-induced mutagenesis after treatment with these agents. We then use single-molecule fluorescence microscopy to measure the localization and dynamics of individual Pol Y1 molecules in live B. subtilis cells. We find that Pol Y1 and Pol Y2 have differing effects on survival and mutagenesis, but that under no circumstances is Pol Y1 strongly recruited to sites of replication upon DNA damage. This study broadens our understanding of TLS in B. subtilis, indicating that there are notable differences in TLS mechanisms across bacteria.

High-resolution global recombination mapping in C. elegans reveals sexual dimorphisms shaped by meiotic chromosomal features and structures

2026-07-14T14:00:00Z

by Zachary D. Bush, John S. Conery, Hannah R. Wilson, Alice F. S. Naftaly, Devin Dinwiddie, Kenneth J. Hillers, Diana E. Libuda

Crossover recombination events during meiosis repair DNA double-strand breaks and ensure accurate chromosome segregation in most organisms. For many species, the genomic distribution of crossovers is nonrandom and sexually dimorphic. While many species evolved kilobase-scale “hotspots” for crossover formation, the Caenorhabditis elegans genome lacks hotspots, and crossovers are enriched across megabase-scale domains. Further, genetic and cytological studies indicate the crossover frequency in C. elegans spermatogenesis is higher relative to oogenesis in many but not all genetic intervals. To determine the genomic features that contribute to the sexually dimorphic recombination landscape in the absence of hotspots, we defined and analyzed the recombination landscape across the whole genome in C. elegans using whole-genome sequencing and high-resolution recombination mapping in single worms bearing recombinant chromosomes from individual sperm and oocytes. We find that the spatial distribution of crossovers is sexually dimorphic on chromosomes I, II, and III, and that the global rate of double-crossover events is 4.7-fold higher in spermatocytes. Additionally, we find that pairing and synapsis may contribute to the sexually dimorphic crossover landscape. In comparison to the spermatocyte crossover landscape, a higher proportion of oocyte crossovers are formed in the domains directly adjacent to the pairing centers of each chromosome. Further, reducing the genetic dosage of the synaptonemal complex central region protein SYP-2, which is a meiotic chromosome structural protein required for homologous chromosome synapsis, reshapes the oocyte crossover landscape to resemble observations in wild-type spermatocytes. Finally, we found that spermatocyte crossovers are partially enriched in H3K36me3-marked euchromatic regions, while many oocyte crossovers are enriched in H3K27me3-marked heterochromatic regions. Taken together, our studies reveal how synaptonemal complex component dosage and local chromatin states influence crossover placement and the sex-specific regulation of meiotic recombination.

Age-based risk estimates for C9orf72^RE-related diseases: Theoretical developments and added value for genetic counseling

2026-07-13T14:00:00Z

by Dominique de Vienne, Damien M. de Vienne

The C9orf72 hexanucleotide repeat expansion is the most common genetic cause of amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD). In genetic counseling, children of mutation carriers are often told that they have a 50% risk of carrying the mutation, but this figure does not take into account the fact that penetrance is age-related, with a unimodal distribution of disease onset around 58 years of age. Using a Bayesian approach, we developed a theory to calculate the probability of carrying the mutation for asymptomatic relatives (children/siblings and grandchildren/niblings) as well as the probability of developing ALS/FDT within a given time frame, based on their age. Using published data on age-related penetrance, we then calculated these probabilities and developed an online simulator that makes it easy to calculate them on a case-by-case basis. The conditional probabilities obtained can be very different from Mendelian values. For example, a 70-year-old asymptomatic child born to a carrier has approximately a 6% risk of being a carrier, which is far from 50%. For grandchildren, taking into account both their age and that of their parents also leads to figures that are much lower than those obtained if only their age were considered. For consultands, the decision to undergo testing is based in part on risk estimates. In this regard, the refined estimates and simulator we propose may prove to be valuable tools for genetic counseling for families affected by ALS/FTD linked to the C9orf72^RE mutation. In addition, the formulas used in this study could also be used to calculate risk estimates for other diseases caused by autosomal dominant mutations with age-dependent penetrance.

Genome-wide cline analysis identifies new locus contributing to a barrier to gene flow across an Antirrhinum hybrid zone

2026-07-13T14:00:00Z

by David L. Field, Sean Stankowski, Taylor Reiter, Jitka Polechova, Desmond Bradley, Daniel M. Richardson, Annabel Whibley, Arka Pal, Daria Shipilina, Louis Boell, Melinda Pickup, Yongbiao Xue, Enrico Coen, Nicholas Barton

Identification of the genomic regions that contribute to reproductive isolation and how they interact is a major goal of evolutionary genetics. Much effort has focused on locating candidate genes and potential barrier loci by scanning genomes for regions of excess differentiation (F_ST). An alternative, and perhaps more robust approach, is to scan for genomic regions exhibiting steep clines in allele frequency across a hybrid zone. We develop a computationally efficient method for approximating cline parameters for large number of loci, and apply it to genomic data from across a hybrid zone between flower colour varieties of Antirrhinum majus (A. m. m var. pseudomajus and A. m. m var. striatum). Most steep clines are clustered in seven genomic regions, only four of which were present from F_ST scans between all pair-wise comparisons. Six of these regions carry previously identified loci that influence flower colour in the hybrid zone. The seventh region harbours a novel locus, RUBIA, modifying magenta intensity. Clines at RUBIA approached fixation on the magenta side of the hybrid zone, whilst remaining polymorphic on the yellow side. This polymorphism on the yellow side may reflect a smaller phenotypic effect of RUBIA in yellow compared to magenta genetic backgrounds. Our findings illustrate how whole-genome cline scans in hybrid zones can robustly detect genomic regions contributing to phenotypic differences and highlight how different reproductive barrier loci interact across the genome.

Local ancestry inference with poorly-matched reference panels

2026-07-13T14:00:00Z

by Sharon R. Browning, Seth D. Temple, Brian L. Browning

The original FLARE method provides computationally efficient and highly accurate local ancestry inference in cases where a closely-matched reference panel is available for each ancestry. In this work, we extend FLARE to incorporate a haplotype clustering algorithm that enables accurate local ancestry inference in scenarios where one or more ancestries do not have a closely-matched reference. This method retains the computational efficiency and accuracy of the original FLARE method while greatly extending its applicability. We apply the new method to data from the Mozabite population from the Human Genome Diversity Project. On the autosomes, we find that the Mozabite samples derive 67% of their ancestry from a population related to European and Middle Eastern populations, with the other 33% of their ancestry coming from a population related to West African populations, with an admixture time 48 generations ago. In contrast, on the X chromosome, we find that the individuals have 76% of their ancestry from a population related to European and Middle Eastern populations.

Sex differences in the regulation and function of cellular immunity in Drosophila

2026-07-10T14:00:00Z

by Alexandra Dvoskin, Kevin Y. L. Ho, Michael Allara, Nicola Janz, Elizabeth Rideout, Juliet R. Girard, Guy Tanentzapf

Sex differences in development and physiology are prevalent in animals. One physiological system with pronounced differences between the sexes is the immune system: the immune response in humans differs between sexes and results in differential susceptibility of males and females to autoimmune diseases, malignancies, and infectious diseases. However, much remains to be discovered about the mechanisms underlying these sex-based differences in immunity. Here, we use the Drosophila hematopoietic organ, the lymph gland, as a model to investigate sex differences in cellular immunity and determine the underlying mechanisms. We find that, in line with their smaller body size, males have smaller lymph glands than females that contain fewer blood progenitors and produce less immune cells. Single cell RNA-seq analysis of the lymph gland showed that they expressed sex determination genes and identified substantial sex-specific differences in gene expression. By manipulating the sexual identity of different cell types in the lymph gland we show that a subset of these sex differences are controlled by organ-intrinsic mechanisms involving the hematopoietic niche. Importantly, we find a differential response between males and females to changes in insulin signaling, an important regulator of the immune response in the niche. Finally, we provide evidence for differences in the cellular immune response following infection between males and females. Overall, our results provide mechanistic insight into how sex differences in immunity are established.

Retraction: The PU.1-Modulated MicroRNA-22 Is a Regulator of Monocyte/Macrophage Differentiation and Acute Myeloid Leukemia

2026-07-09T14:00:00Z

by The PLOS Genetics Editors

Highly frequent undesired insertional mutagenesis during Drosophila genome editing

2026-07-09T14:00:00Z

by Emma Källstig, Evelyne Ruchti, Medha Raman, Jamshid Asadzadeh, Bernard L. Schneider, Brian D. McCabe

CRISPR/Cas9 based genome editing employing Homology Directed Repair (HDR) from template vector sequences is a widely used technique to enable precise insertions, deletions or modifications to genes. Here, we describe an undesired and highly frequent editing event when using conventional CRISPR/Cas9 plus HDR methods for Drosophila melanogaster germline genome editing. We find that the template vector employed for HDR repair unwantedly and commonly inserts into the genome. We observe this deviation from the desired edit at multiple genomic locations, with different HDR vectors and with multiple genome editing designs. To avoid these events, we have generated a novel HDR template vector that enables animals with these undesired insertions to be identified and excluded. Our results suggest that HDR based genome edited animals must be carefully screened for unwanted vector template genomic integration in order to avoid misleading interpretations of genome editing outcomes.

Multi-regional transcriptomic profiling reveals divergent molecular mechanisms in ALS-related neurodegeneration

2026-07-08T14:00:00Z

by Yu-Wen Hsu, Yu-Ning Lu, Mingming Liu, Jiou Wang

Neurodegenerative disorders including amyotrophic lateral sclerosis (ALS) remain largely unsolved, with complex etiology yet to be fully elucidated. The most common genetic cause of ALS in both familial and sporadic cases is the expansion of a hexanucleotide repeat in the C9orf72 gene. To systematically dissect the molecular landscape of ALS, we performed integrative transcriptomic analyses across multiple central nervous system regions from ALS patients carrying pathological C9orf72 repeat expansions (ALS-C9) and those without the mutation (ALS-non-C9). In parallel, we performed transcriptome-wide cell-type deconvolution to assess the cellular composition of neuronal and non-neuronal populations. We identified a set of dysregulated molecular pathways that were consistently altered in both ALS-C9 and ALS-non-C9 patients, suggesting shared pathogenic mechanisms. Distinct gene-specific alterations also pointed to divergent subtype-dependent molecular trajectories. Gene-specific alterations were also associated with short clinical duration in ALS-non-C9, highlighting a sex-dependent immunological contribution to disease outcome. Our cross-regional integrative transcriptomic analyses reveal both convergent and divergent molecular and cellular features between ALS-C9 and ALS-non-C9 subgroups, underscoring the clinical heterogeneity of ALS and providing a framework for subtype- and sex-specific therapeutic stratifications.

Genetic survey of biomarkers at early and mid-pregnancy identifies pregnancy-specialized immune regulation

2026-06-30T14:00:00Z

by Merve Cakir, Michela Traglia, Stacey Alexeeff, Jennifer L. Ames, Paul Ashwood, Luke P. Grosvenor, Erica P. Gunderson, Danielle H. J. Kim, Jane W. Liang, Yinge Qian, Elizabeth Sahagun, Robert Yolken, Judy Van de Water, Lisa A. Croen, Lauren A. Weiss

Much remains unknown about the genetics of immune system changes during pregnancy. We used SNP data in a pregnancy cohort to genetically investigate 47 immune biomarkers at two timepoints, along with change between timepoints (Δ). We identified 19 biomarkers with significant SNP-based heritability and 34 with genome-wide significant signals, demonstrating genetic regulation. The same biomarkers measured in early- and mid-pregnancy shared about half of significant associations across timepoints, with enrichment for immune pathways. In contrast, Δ showed enrichment in transcription factors and developmental processes. About half of suggestive associations overlapped with non-pregnancy associations. However, these data leave a substantial fraction of potentially timepoint-specific and pregnancy-unique findings. Nearby genes were enriched for high expression in decidual cells at the maternal-fetal interface, reinforcing the novelty of our results. We additionally explored the relationship between immune genetic associations and prior GWAS of pregnancy complications. Overall, we present the first two-timepoint genetic study of immune profile in pregnancy.

Argonaute proteins orchestrate Meiotic Sex Chromosome Inactivation and timing of the spermatogenic transcriptional program

2026-06-29T14:00:00Z

by Maria de las Mercedes Carro, Alexis Dziubek, Amanda Touey-May, Elizabeth A. Popkowski, Mark Abdelmassih, Leah E. Simon, Stephanie L. Tanis, Faraz Ahmed, Jennifer K. Grenier, Andrew Grimson, Paula E. Cohen

Argonaute proteins (AGO) are best known for their role in microRNA-mediated post-transcriptional gene silencing. Here, we demonstrate that AGO3 and AGO4, but not AGO2, localize to the sex chromatin of pachytene spermatocytes, where they are required for the transcriptional silencing of XY-linked genes that characterizes Meiotic Sex Chromosome Inactivation (MSCI). Previous findings showed that deletion of Ago4 (Ago4^-/-) mildly impairs MSCI and normal spermatozoa production. By contrast, loss of Ago3 (Ago3^-/-) does not produce these defects, while combined deletion of Ago1, Ago3, and Ago4 (Ago413^-/-) leads to severely reduced fertility, accompanied by disrupted autosomal and sex chromosome gene regulation and altered chromatin accessibility in spermatocytes. In Ago413^-/- mice, premature overexpression of spermiogenesis genes during prophase I results in reduced sperm production, abnormal sperm morphology, and impaired fertilization capacity. Together, AGO3 and AGO4 act during prophase I to ensure the timely expression of meiosis-related genes during prophase I while maintaining repression of spermiogenesis-associated genes. These results indicate that AGO3 and AGO4 act in a coordinated fashion in the male germline to orchestrate cell progression in spermatogenesis through temporal regulation of autosomal and sex chromosome genes.

Multiple instance fine-mapping: Predicting causal regulatory variants with a deep sequence model

2026-06-29T14:00:00Z

by Alexander Rakowski, Christoph Lippert

Identifying causal genetic variants in a computational manner remains an open problem. Training end-to-end prediction models is not possible without large ground-truth datasets, while results of genome-wide association studies (GWAS) are entangled by linkage disequilibrium (LD), and gene expression datasets do not contain genetic variation at individual-level. Here, we propose Multiple Instance Fine-mapping (MIFM) – a multiple instance learning (MIL) objective to overcome the lack of strong labels by grouping putatively causal variants together based on their LD scores. Using MIFM, we trained a deep classifier on a dataset aggregating over 13,000 GWAS to predict causal variants based on their underlying DNA sequences. We validated variants prioritized by MIFM by constructing polygenic risk scores which transferred better to different target ancestries. Furthermore, we demonstrated how MIFM can be used to disentangle effect sizes of highly-correlated variants to better fine-map GWAS results.

Microtubule stiffening by the doublecortin-domain protein ZYG-8 contributes to mitotic spindle orientation during zygote division in Caenorhabditis elegans

2026-06-29T14:00:00Z

by Louis Cueff, Loïc Schmitt, Ewen Huet, Sylvain Pastezeur, Méline Coquil, Talia Savary, Anouk Sénard, Jacques Pécréaux, Hélène Bouvrais

In the Caenorhabditis elegans zygote, mutations in zyg-8^DCLK1, the sole Doublecortin-family member, disrupt mitotic spindle positioning, as seen by immunofluorescence. Doublecortin proteins bind microtubules and are thought to stabilise or rigidify them. In the zygote, ZYG-8 only modestly affects microtubule growth and nucleation. We thus investigated whether these moderate dynamic perturbations alone could explain the spindle mispositioning observed in zyg-8 mutants. Using three complementary genetic perturbations—RNAi-mediated depletion of ZYG-8, its overexpression, and the thermosensitive zyg-8(or484ts) mutant (that disrupts microtubule binding)—we observed altered spindle pole oscillations and changes in microtubule cortical-contact behaviour, indicative of impaired cortical forces. Importantly, these phenotypes could not be fully explained by previously reported alterations in microtubule dynamics, suggesting an additional mechanism. Our findings indicate that ZYG-8 increases microtubule rigidity: ZYG-8 depletion or mutation led to more frequent microtubule bending and higher curvature and tortuosity. Simulations confirmed that reduced rigidity prolongs cortical contact lifetimes, an effect we experimentally observed in zyg-8(RNAi) embryos. Using custom biophysical assays, we showed that microtubule softening in zyg-8(RNAi) embryos and zyg-8 mutants reduced the efficiency of centring forces, leading to exaggerated spindle-pole oscillations. In mutants, the largest oscillations caused spindle poles to move closer to the cell periphery, preventing re-centring and resulting in spindle mispositioning and misorientation during late anaphase. Importantly, reducing cortical pulling forces rescued orientation defects, highlighting the importance of balanced pulling-pushing forces for proper spindle positioning. We propose that sufficient microtubule rigidity is essential for generating effective cortical pushing forces, potentially in synergy with other microtubule properties, which contribute to centring mechanisms that ensure accurate spindle orientation in late mitosis. Given that DCLK1 is frequently deregulated in human cancers and that accurate spindle positioning is essential for maintaining cell proliferation-differentiation balance, these findings may have implications for understanding how disruptions in microtubule mechanics contribute to carcinogenesis.

Genome wide association study meta-analysis of neuropathologic lesions of Alzheimer’s disease and related dementias in a multi-site autopsy cohort

2026-06-29T14:00:00Z

by Brenna Cholerton, Dana Godrich, Jeremy Pasteris, Joe Rivero, Eden R. Martin, Brian W. Kunkle, Adam C. Naj, Kara L. Hamilton-Nelson, Hui Wang, Wan-Ping Lee, Logan Dumitrescu, Timothy J. Hohman, Richard Mayeux, Eric B. Larson, Paul K. Crane, C. Dirk Keene, Caitlin S. Latimer, Shubhabrata Mukherjee, Julia K. Kofler, M. Ilyas Kamboh, David A. Bennett, Laura Molina-Porcel, Michael Cuccaro, Margaret A. Pericak-Vance, Tatjana Rundek, William K. Scott, Walter Kukull, Gerard Schellenberg, Alzheimer’s Disease Genetics Consortium , Gary W. Beecham, Thomas J. Montine

Understanding the genetic foundations of dementia is critical to unraveling its complex molecular basis. Given that a clinical diagnosis of Alzheimer’s disease (AD) dementia often results from interplay between multiple underlying neuropathologic co-morbidities, previous genome-wide association studies (GWAS) of clinically diagnosed AD are restricted in their ability to translate genetic associations to potential targeted therapeutics. The current study seeks to address these limitations by presenting the largest GWAS to date (n = 12,509) of neuropathologic hallmarks of AD and AD related dementias (ADRDs). We further performed a candidate-variant analysis using loci previously identified in GWAS of clinically diagnosed AD dementia and Parkinson’s disease (PD). Finally, we conducted heritability and genetic correlation analyses using linkage disequilibrium (LD) score regression. We found broad genome-wide significant associations with APOE across AD and ADRDs but not cerebrovascular disease and vascular brain injury. We further identified 12 significant loci across 10 neuropathologic phenotypes, including 5 loci previously implicated in GWAS of clinical AD and ADRDs (variants on BIN1, PICALM/ EED, TMEM106B, GRN, and SNCA/ SNCA-AS1) and 7 novel genome-wide associations (variants on EPHA5, PSMG1, LINC00276, VAPA, LINC00290, DOCK4 and SLAIN2/ SLC10A4). Our analysis of AD and PD clinical candidate variants demonstrated several that were associated with AD neuropathologic change and Lewy body disease, as well as substantial overlap with neuropathologic lesions other than the primary neuropathologic hallmarks of these diseases. Heritability analyses demonstrated heritability that was high for amyloid plaques (78%) relative to prior clinical AD heritability analyses, intermediate for TDP-43 inclusions (41%), and low for remaining AD and ADRD pathologic features. This study underscores the importance of investigating the underlying neuropathologic hallmarks of AD and ADRDs as a step toward refining the translation of genetic associations to biomarker interpretation and development of targeted therapeutics.

Nuclear ubiquitin-conjugating enzyme TrUbc4 and F-box protein TrFwd1-mediated modification of Cre1 in Trichoderma reesei establishes a regulatory mechanism for carbon catabolite repression

2026-06-26T14:00:00Z

by Gen Xu, Yanli Cao, Yuxiao Xia, Shanshan Jiang, Weixin Zhang, Xiangfeng Meng, Weifeng Liu

Carbon catabolite repression (CCR) mediated by the transcriptional repressor Cre1 represents a major mechanism ensuring the energy-efficient cellulase production in the model cellulolytic fungus Trichoderma reesei. However, largely unknown is the regulatory pathway governing CCR. In this study, we identified a nuclear ubiquitination system targeting Cre1 to facilitate the induced cellulase gene expression. Either repression of Trubc4 encoding an E2 (ubiquitin-conjugating enzyme) or deletion of Trfwd1 encoding an F-box protein significantly compromised the induced cellulase biosynthesis. However, combinatorial repression of cre1 suppressed the phenotypic defects resultant from mutations of Trubc4 or Trfwd1. Further analyses demonstrated that TrUbc4 and TrFwd1 collaboratively mediated the ubiquitination of Cre1. Impaired ubiquitination of Cre1 at K361 resulted in its enhanced binding to cellulase gene promoters even under cellulose inducing conditions. This persistent Cre1 binding in turn competitively excluded the functional promoter occupancy of the transcriptional activator Xyr1 required for full cellulase gene expression. These results thus support that Cre1 ubiquitination constitutes a primary mechanism to relieve CCR to ensure the efficient cellulase induction. The present work also highlights the importance of protein ubiquitination for control of carbohydrate utilization and biotechnologically relevant enzyme production in industrial filamentous fungi including Trichoderma reesei.

Cold-responsive interaction between MdRAD23D1 and MdMYB15 confers cold stress tolerance via the CBF pathway in apple (Malus domestica)

2026-06-25T14:00:00Z

by Xiaoli Zhang, Benzhou Zhao, Xiaoyan Li, Hui Xia, Fengwang Ma, Dong Liang, Xiaoqing Gong

Low temperature is a major environmental factor that impairs plant growth and development, posing a significant threat to crop yield and quality. RAD23 (RADIATION SENSITIVE23) proteins belong to the UBL-UBA (Uiquitin-like-ubiquitin associated) family and function as shuttle factors in the UPS (ubiquitin proteasome system). Although UBL-UBA proteins are known regulators of plant stress responses, the function and mechanism of RAD23 in apple under cold stress are poorly understood. Here, we demonstrated that MdRAD23D1 is induced by 4 °C and positively regulates cold tolerance. Silencing MdRAD23D1 impaired cold tolerance in both apple plants and calli. Conversely, its overexpression enhanced cold tolerance in transgenic tobacco, and apple calli and plants. We further demonstrated that MdRAD23D1 interacted with MdMYB15 protein via in vivo and in vitro assays. MdMYB15 functions as a negative regulator of cold stress tolerance. This is evidenced by the enhanced cold tolerance in apple calli and plants in which MdMYB15 expression was silenced, contrasted with the reduced tolerance in materials of overexpressing MdMYB15. Furthermore, yeast one-hybrid (Y1H), dual-luciferase (Dual-LUC), and electrophoretic mobility shift assays (EMSA) showed that MdMYB15 could bind to the promoters of CBF1, CBF2, and CBF3 and inhibit the expressions of the corresponding genes. In addition, MdRAD23D1 promoted MdMYB15 degradation under cold stress, thus enhancing the cold tolerance of apple. In summary, we proposed a mechanism for the response of apple to cold stress that is mediated by the ‘MdRAD23D1-MdMYB15-MdCBFs’ modula, which enhances our understanding of the regulation of cold tolerance in apple by UBL-UBA protein.

Exploring mechanisms of scar-free skin wound healing in adult zebrafish in comparison to mouse

2026-06-24T14:00:00Z

by İsmail Küçükaylak, Kai Halwas, Francisco Javier Martínez Morcillo, Nils Reiche, Manuel Metzger, Petra Comelli, Birgit Voigt, Jürgen Brinckmann, Sabine Eming, Matthias Hammerschmidt

Adult zebrafish have the ability to perfectly regenerate their skin after injury without leaving a scar behind. Yet, they intermediately form a collagen-rich granulation tissue that later fully regresses. In contrast, adult mammals lose this ability, resulting in persistent tissue fibrosis and scarring. We performed single-cell RNA sequencing and first HCR-based spatial transcriptomics to characterize the dynamics and heterogeneity of involved cell types during different stages of zebrafish cutaneous wound healing, focusing on macrophages and fibroblasts. Macrophage subclusters display pro-inflammatory and/or anti-inflammatory/pro-repair characteristics, and fibroblast subclusters characteristics of extracellular matrix formation and degradation, which largely co-exist during all stages of wound healing. Some wound-specific cells have a signature similar to that of myofibroblasts implicated in fibrotic healing in mammals. However, in contrast to mammalian myofibroblasts, they lack collagen expression, suggesting that they might only share the beneficial, but not the detrimental roles of their mammalian counterparts. Strikingly, zebrafish fibroblasts, in addition to expressing anti-fibrotic genes, express multiple genes with described pro-fibrotic effects in mammalian models. One of them is plod2, which encodes lysylhydroxylase 2. In cutaneous mouse wounds, Plod2 is induced in fibroblasts by the macrophage-released Resistin-like molecule RELMα encoded by the Retlna gene, promoting the formation of DHLNL collagen crosslinks and thereby less resolvable fibrotic tissue. retln genes are absent from the zebrafish genome; nevertheless, plod2 expression is initiated in zebrafish dermal fibroblasts upon wounding, in this case via TGFβ signaling, accompanied by increased collagen DHLNL crosslinking. Yet, both transgenic overexpression and genetic knock-out of plod2 do not interfere with granulation tissue formation and regression, pointing to additional pathways assuring the resolution of temporary fibrosis in zebrafish skin wounds even in the presence of strong collagen crosslinking.

PLOS Genetics: New Articles

Recurrent evolution of cryptic triploids in cultivated enset increases yield

Partitioning of the truncated insulin receptor DAF-2B between homodimers and heterodimers influences insulin signaling in C. elegans

Photoperiodic patterns in miRNA-mRNA pairs and tRNA fragments revealed by time-course co-sequencing in Arabidopsis

Multi-ancestry colocalization approaches

Cross-family and phage-specific gene requirements for Klebsiella infection revealed by scalable RB-TnSeq genetic screens

A tumor-suppressive role of the PRC1 Polycomb epigenetic complex in the maintenance of adult Drosophila intestinal stem cell identity

Identifying severe COVID-19 risk variants modulating enhancer reporter activity in lung cells

Contrasting evolutionary patterns of helper and sensor NRC NLRs in lettuce reflect functional divergence following subfunctionalization

Wiz regulates clustered protocadherin genes by restricting CTCF/cohesin loop extrusion in a genomic-distance biased manner

Apical spectrin organizes cortical actin filament bundles to pattern C. elegans cuticle ridges

A genomic-led strategy to anticipate drug safety effects

A generalized test of genotype–phenotype causality in population-sampled nuclear families

An ancestral transmembrane transcription factor couples cell envelope regulation and the SOS response in Caulobacter crescentus

The B. subtilis translesion polymerase Pol Y1 is not strongly recruited to sites of replication upon different types of DNA damage

High-resolution global recombination mapping in C. elegans reveals sexual dimorphisms shaped by meiotic chromosomal features and structures

Age-based risk estimates for C9orf72RE-related diseases: Theoretical developments and added value for genetic counseling

Genome-wide cline analysis identifies new locus contributing to a barrier to gene flow across an Antirrhinum hybrid zone

Local ancestry inference with poorly-matched reference panels

Sex differences in the regulation and function of cellular immunity in Drosophila

Retraction: The PU.1-Modulated MicroRNA-22 Is a Regulator of Monocyte/Macrophage Differentiation and Acute Myeloid Leukemia

Highly frequent undesired insertional mutagenesis during Drosophila genome editing

Multi-regional transcriptomic profiling reveals divergent molecular mechanisms in ALS-related neurodegeneration

Genetic survey of biomarkers at early and mid-pregnancy identifies pregnancy-specialized immune regulation

Argonaute proteins orchestrate Meiotic Sex Chromosome Inactivation and timing of the spermatogenic transcriptional program

Multiple instance fine-mapping: Predicting causal regulatory variants with a deep sequence model

Microtubule stiffening by the doublecortin-domain protein ZYG-8 contributes to mitotic spindle orientation during zygote division in Caenorhabditis elegans

Genome wide association study meta-analysis of neuropathologic lesions of Alzheimer’s disease and related dementias in a multi-site autopsy cohort

Nuclear ubiquitin-conjugating enzyme TrUbc4 and F-box protein TrFwd1-mediated modification of Cre1 in Trichoderma reesei establishes a regulatory mechanism for carbon catabolite repression

Cold-responsive interaction between MdRAD23D1 and MdMYB15 confers cold stress tolerance via the CBF pathway in apple (Malus domestica)

Exploring mechanisms of scar-free skin wound healing in adult zebrafish in comparison to mouse

Age-based risk estimates for C9orf72^RE-related diseases: Theoretical developments and added value for genetic counseling