Summary of Nature publications, focusing on contents relevant to AI and life sciences
Nucleosomes, Animals, Mice, DNA, Histones, Hepatocyte Nuclear Factor 3-beta, Promoter Regions, Genetic, Transcription Factors, Chromatin Assembly and Disassembly, Chromatin, Mouse Embryonic Stem Cells, DNA Footprinting, Humans
Researchers developed a computational method called IDLI that maps structural variations in nucleosomes along individual DNA fibers using long-read single-molecule footprinting. Applying it to mouse embryonic stem cells, they found over 85% of nucleosomes have accessible DNA within their structure, termed 'distortion.' These distortion patterns varied by genomic region and gene expression, correlated with transcription factor binding motifs, and were regulated by transcription factors in experiments. IDLI also detected distortion at pioneer transcription factor FOXA2 binding sites during cell differentiation in human cells and mouse liver, and mouse genetics confirmed FOXA2's direct role in shaping nucleosome structure. The work reveals widespread, regulated nucleosome variability at the single-molecule level and provides a tool for studying transcription factor binding and chromatin regulation.
Humans, Alleles, Asia, DNA, Ancient, Europe, Evolution, Molecular, Gene Frequency, History, Ancient, Phenotype, Selection, Genetic
Researchers developed a new computational method to detect directional selection in ancient DNA time series by testing for consistent allele frequency trends over time, rather than relying on signals of classic hard sweeps. Applying it to nearly 16,000 West Eurasian ancient genomes, they found hundreds of alleles under strong directional selection over the past ten millennia, despite the rarity of full sweeps. Notably, polygenic combinations of alleles linked to complex traits shifted by roughly one standard deviation, including decreased predicted body fat and schizophrenia risk, alongside increased cognitive performance scores, though these were measured in modern industrialized populations and may not reflect past adaptive phenotypes. The approach also yielded selection coefficient estimates for 9.7 million variants, offering a tool to explore how Darwinian selection connects allele effects to the genetic architecture of complex traits.
Animals, Female, Mice, Cryoelectron Microscopy, Cytoplasm, Embryonic Development, Models, Molecular, Multiprotein Complexes, Oocytes, Protein-Arginine Deiminase Type 6, Tubulin, Ubiquitin-Protein Ligases, Ubiquitination
Using cryo-electron microscopy and AI-based modeling, researchers resolved the molecular architecture of native cytoplasmic lattices (CPLs) in mouse oocytes. These storage structures are built from at least 13 proteins forming a megadalton complex, including maternal effect factors like PADI6 and the subcortical maternal complex. Crucially, the lattices incorporate proteins essential for early embryogenesis: unpolymerized α- and β-tubulin dimers, plus a suite of ubiquitination machinery—the E3 ligase UHRF1, E2 enzymes, and substrate adapters—thereby stably stockpiling them. This shows oocytes safeguard vital proteins by assembling them into highly stable supramolecular complexes. The work provides a structural basis for understanding how disruptions to stored maternal factors cause infertility and developmental disorders, and illuminates a general storage mechanism in mammalian eggs.
Animals, Female, Humans, Mice, Pregnancy, Brain, Dopamine, Hippocampus, Histones, Neuronal Plasticity, Postpartum Period, Protein Processing, Post-Translational, Transcription, Genetic
The study investigates how pregnancy and postpartum experiences cause lasting changes in the maternal brain. Using brain-wide transcriptomic profiling in mice, the researchers identified the dorsal hippocampal formation as a key site of gene expression remodeling. Single-cell RNA sequencing combined with a maternal-pup separation model showed that chronic postpartum stress disrupts these adaptations by altering dopamine signaling, which affects a specific histone modification called H3 dopaminylation. This modification drives downstream changes in gene expression and behavior. In human dorsal subiculum samples, they found similar parity-related patterns of H3 dopaminylation and transcription. Chemogenetically suppressing dopamine release into the dorsal hippocampus in virgin female mice replicated key epigenomic and behavioral features of reproductive experience, confirming dopamine's sufficiency. The findings establish dopamine as a central regulator of parity-induced neuroadaptations in mice and humans, revealing a fundamental mechanism by which reproductive experience remodels the brain for long-term behavioral changes.
Actinobacteria, Anti-Bacterial Agents, Bacteria, Drug Resistance, Bacterial, Drug Resistance, Microbial, Gene Transfer, Horizontal, Genes, Bacterial, Global Warming, Grassland, Selection, Genetic, Soil, Soil Microbiology, Time Factors
A decade-long field experiment in grassland soils shows that climate warming significantly amplifies antibiotic resistance. The study found that warming raised overall resistance gene abundance by nearly a quarter, with specific increases in genes conferring resistance to glycopeptides and rifamycin. The effect was linked to the enrichment of Actinomycetota bacteria, including potential plant pathogens, alongside enhanced gene mobility. Phenotypic tests on bacterial isolates confirmed heightened resistance to multiple antibiotics under warming. Mechanistically, the rise appears driven by co-selection: resistance genes often sit physically near genes for adaptive traits like thermal tolerance and nitrogen assimilation, and warming favors these traits, inadvertently promoting the linked resistance genes—a process amplified by horizontal gene transfer. The work highlights climate change as a hidden driver of antimicrobial resistance across genomic, ecological, and evolutionary scales, with consequences for health and environmental management.
Humans, RNA, Small Nuclear, Genes, Recessive, Spliceosomes, Genes, Dominant, Microcephaly, Gene Editing, Phenotype, RNA Splicing, Dwarfism, Fetal Growth Retardation, Osteochondrodysplasias
Researchers used saturation genome editing to test the functional impact of nearly all possible genetic variants in RNU4-2, a non-protein-coding gene that produces a component of the spliceosome. The resulting fitness-based scores successfully distinguished variants that cause ReNU syndrome—a neurodevelopmental disorder—from harmless population variants, outperforming computational predictors. The scores pinpointed the disorder's critical region at single-nucleotide resolution, clarified the pathogenicity of uncertain variants, and correlated with symptom severity and splicing disruption. Beyond ReNU syndrome, the researchers identified damaging variants in regions important for spliceosome interactions, which were found to cause a separate, newly recognized recessive neurodevelopmental disorder. This work provides a comprehensive functional map of the gene, improving diagnostic accuracy and informing future therapeutic strategies.
Animals, Female, Mice, Cryoelectron Microscopy, Cytoplasm, Models, Molecular, Oocytes, Protein Multimerization, Protein Subunits, Protein-Arginine Deiminase Type 6, Antigens, Egg Proteins
Mammalian eggs rely on fibrous structures known as cytoplasmic lattices (CPLs) for maturation and early embryo development, yet their architecture was largely unknown. Using cryo-electron microscopy on CPLs isolated from mouse oocytes, researchers resolved the full molecular structure of these filaments. They identified 14 protein subunits arranged into repeating modules, each combining a U-shaped basket and an adapter ring. The basket is built around PADI6, which forms a ten-dimer ring, while the adapter ring is a symmetric circular assembly of NLRP4F, SCMC, and ZBED3 proteins. The two adjacent baskets are physically linked by SCMC dimers through extensive interactions, providing the repetitive connection that forms the long CPL filament. This high-resolution blueprint explains how the lattice is assembled and provides a foundation for investigating how defects in CPL contribute to female infertility and early embryonic failure in mammals.
Animals, Female, Male, Aging, Longevity, Mice, Life Expectancy, Epistasis, Genetic, Sex Characteristics, Body Weight, Quantitative Trait Loci, Body Size
Researchers tracked genetic effects on lifespan and body-mass-related mortality in a large mouse cohort, following 6,438 pubescent animals down to 559 that survived past 1,100 days. They identified 29 lifespan-associated loci with age- and sex-specific effects, often flipping their influence from harmful to beneficial depending on life stage. Separately, 30 loci tied to body mass and survival showed that being larger raises mortality risk in young mice but lowers it in older ones. These effects were consistently stronger in males, and the loci formed genetic interaction networks that were entirely sex-specific. The work links evolutionary theories of aging to concrete molecular pathways and could help guide future interventions for extending healthy lifespan.
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