High planting density boosts crop yields but also heightens pest and pathogen risks. How plants adapt their defenses under these conditions remains unclear. In this study, we reveal that maize enhances its defense in hig...High planting density boosts crop yields but also heightens pest and pathogen risks. How plants adapt their defenses under these conditions remains unclear. In this study, we reveal that maize enhances its defense in high-density conditions through a plant-soil feedback mechanism triggered by the leaf volatile linalool. Linalool activates jasmonate signaling in neighboring plants and promotes root exudation of benzoxazinoids, especially 2-(2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one)-β-d-glucopyranose (HDMBOA-Glc). These exudates in turn reshape the rhizosphere microbiome composition to favor growth of specific bacterial taxa that trigger broad-spectrum resistance, albeit at the cost of maize growth. This microbiome-driven feedback loop is governed by salicylic acid signaling. Our findings uncover intricate chemical signaling in high-density cropping, which is instrumental for improving soil health and designing sustainable strategies that balance the trade-off between plant growth and defense.
Extreme metabolic adaptations can elucidate genetic programs that govern mammalian metabolism. Here, we used convergent evolutionary changes in hibernating lineages to define conserved cis-regulatory elements (CREs) and...Extreme metabolic adaptations can elucidate genetic programs that govern mammalian metabolism. Here, we used convergent evolutionary changes in hibernating lineages to define conserved cis-regulatory elements (CREs) and metabolic programs. We characterized mouse hypothalamus gene expression and chromatin dynamics across fed, fasted, and refed states and then used comparative genomics of hibernating versus nonhibernating lineages to identify cis elements with convergent changes in hibernators. Multi-omics approaches pinpointed CREs, hub genes, regulatory programs, and cell types underlying lineage divergence. Hibernators accumulated loss-of-function effects for CREs regulating hypothalamic responses, and the refeeding period after fasting served as a key phase for molecular processes with convergent evolutionary changes. This work provides a genetic framework for harnessing hibernator adaptations to understand human metabolic control.
The challenge of producing food at low monetary cost comes with high environmental impacts as yield maximization by excessive fertilization and chemical pest control drive farmers away from using the natural multifunctio...The challenge of producing food at low monetary cost comes with high environmental impacts as yield maximization by excessive fertilization and chemical pest control drive farmers away from using the natural multifunctional potential of soils. We show how the ecological concept of plant-soil feedback can be used to restore the capacity of agricultural soils to provide nutrients, suppress pathogens, and enhance crop resilience sustainably. We review how recent advances in molecular and multiomic methods, soil management, and crop diversification reduce negative and promote positive plant-soil feedback, emphasizing the need for rhizosphere microbiome engineering and soil restoration strategies. Applying nature-based plant-soil feedback principles would enhance transformation to more sustainable agricultural practices that secure food production by restoring natural soil functions, while simultaneously mitigating climate change.
Structural foundation models help to elucidate and reprogram molecular biology.Structural foundation models help to elucidate and reprogram molecular biology.
Matriarchs and foragers emerge as important players in early farming villages.Matriarchs and foragers emerge as important players in early farming villages.
is a morphologically well-documented Early Pleistocene hominin species from southern Africa with no genetic evidence reported so far. In this work, we describe the mass spectrometric sequencing of enamel peptides from fo...is a morphologically well-documented Early Pleistocene hominin species from southern Africa with no genetic evidence reported so far. In this work, we describe the mass spectrometric sequencing of enamel peptides from four ~2 million-year-old dental specimens attributed morphologically to from the site of Swartkrans in South Africa. The identification of AMELY-specific peptides enabled us to assign two specimens to male individuals, whereas semiquantitative mass spectrometric data analysis attributed the other two to females. A single amino acid polymorphism and the enamel-dentine junction shape variation indicated potential subgroups present within southern African . This study demonstrates how palaeoproteomics can help distinguish sexual dimorphism from other sources of variation in African Early Pleistocene hominins.
Heterotrophic bacteria and archaea ("heteroprokaryotes") drive global carbon cycling, but how to quantitatively organize their functional complexity remains unclear. We generated a global-scale understanding of marine he...Heterotrophic bacteria and archaea ("heteroprokaryotes") drive global carbon cycling, but how to quantitatively organize their functional complexity remains unclear. We generated a global-scale understanding of marine heteroprokaryotic functional biogeography by synthesizing genetic sequencing data with a mechanistic marine ecosystem model. We incorporated heteroprokaryotic diversity into the trait-based model along two axes: substrate lability and growth strategy. Using genetic sequences along three ocean transects, we compiled 21 heteroprokaryotic guilds and estimated their degree of optimization for rapid growth (copiotrophy). Data and model consistency indicated that gradients in grazing and substrate lability predominantly set biogeographical patterns, and we identified deep-ocean "slow copiotrophs" whose ecological interactions control the surface accumulation of dissolved organic carbon.
Brazil, the largest Latin American country, is underrepresented in genomic research despite boasting the world's largest recently admixed population. In this study, we generated 2723 high-coverage whole-genome sequences...Brazil, the largest Latin American country, is underrepresented in genomic research despite boasting the world's largest recently admixed population. In this study, we generated 2723 high-coverage whole-genome sequences from the Brazilian population, including urban, rural, and riverine communities representing diverse ethnic backgrounds. We reveal the impressive genomic diversity of Brazilians, identifying >8 million previously unknown variants, including 36,637 predicted deleterious and potentially affecting population health. We found a positive correlation between these deleterious variants and ancestry. Brazilian genomes are a global haplotype mosaic shaped by nonrandom mating, with peak admixture in the 18th and 19th centuries. Within this diversity, ancestry-specific haplotypes exhibit an uneven spatiotemporal distribution. We also identified putatively selected genes in this diverse population, primarily linked to fertility, immune response, and metabolic traits.
Gusareva ES, Ghosh AG, Kharkov VN
… +45 more, Khor SS, Zarubin A, Moshkov N, Kalsi N, Ratan A, Heinle CE, Cooke N, Bravi CM, Smolnikova MV, Tereshchenko SY, Kasparov EW, Khitrinskaya I, Marusin A, Razhabov MO, Golubenko MV, Swarovskaya M, Kolesnikov NA, Vagaitseva KV, Eremina ER, Sukhomyasova A, Shtygasheva O, Panicker D, Ang PN, Lee CF, Koh Y, Leong ST, Park C, Lohar SR, Yap ZH, Ng SG, Dacanay J, Drautz-Moses DI, Ramli NAB, Tokunaga K, McGonigle I, Danjoh I, Moreno-Estrada A, Tajima A, Tanabe H, Nakamura Y, Nakagome S, Tatarinova TV, Stepanov VA, Schuster SC, Kim HL
Genome sequencing of 1537 individuals from 139 ethnic groups reveals the genetic characteristics of understudied populations in North Asia and South America. Our analysis demonstrates that West Siberian ancestry, represe...Genome sequencing of 1537 individuals from 139 ethnic groups reveals the genetic characteristics of understudied populations in North Asia and South America. Our analysis demonstrates that West Siberian ancestry, represented by the Kets and Nenets, contributed to the genetic ancestry of most Siberian populations. West Beringians, including the Koryaks, Inuit, and Luoravetlans, exhibit genetic adaptation to Arctic climate, including medically relevant variants. In South America, early migrants split into four groups-Amazonians, Andeans, Chaco Amerindians, and Patagonians-~13,900 years ago. Their longest migration led to population decline, whereas settlement in South America's diverse environments caused instant spatial isolation, reducing genetic and immunogenic diversity. These findings highlight how population history and environmental pressures shaped the genetic architecture of human populations across North Asia and South America.
Sanguankiattichai N, Chandrasekar B, Sheng Y
… +17 more, Hardenbrook N, Tabak WWA, Drapal M, Kaschani F, Grünwald-Gruber C, Krahn D, Buscaill P, Yamamoto S, Kato A, Nash R, Fleet G, Strasser R, Fraser PD, Kaiser M, Zhang P, Preston GM, van der Hoorn RAL
The extracellular space (apoplast) in plants is a key battleground during microbial infections. To avoid recognition, the bacterial model phytopathogen pv. DC3000 produces glycosyrin. Glycosyrin inhibits the plant-secr...The extracellular space (apoplast) in plants is a key battleground during microbial infections. To avoid recognition, the bacterial model phytopathogen pv. DC3000 produces glycosyrin. Glycosyrin inhibits the plant-secreted β-galactosidase BGAL1, which would otherwise initiate the release of immunogenic peptides from bacterial flagellin. Here, we report the structure, biosynthesis, and multifunctional roles of glycosyrin. High-resolution cryo-electron microscopy and chemical synthesis revealed that glycosyrin is an iminosugar with a five-membered pyrrolidine ring and a hydrated aldehyde that mimics monosaccharides. Glycosyrin biosynthesis was controlled by virulence regulators, and its production is common in bacteria and prevents flagellin recognition and alters the extracellular glycoproteome and metabolome of infected plants. These findings highlight a potentially wider role for glycobiology manipulation by plant pathogens across the plant kingdom.
Tracking the geographic origins of genetic ancestors reveals past human migrations.Tracking the geographic origins of genetic ancestors reveals past human migrations.
Describing the distribution of genetic variation across individuals is a fundamental goal of population genetics. We present a method that capitalizes on the rich genealogical information encoded in genomic tree sequence...Describing the distribution of genetic variation across individuals is a fundamental goal of population genetics. We present a method that capitalizes on the rich genealogical information encoded in genomic tree sequences to infer the geographic locations of the shared ancestors of a sample of sequenced individuals. We used this method to infer the geographic history of genetic ancestry of a set of human genomes sampled from Europe, Asia, and Africa, accurately recovering major population movements on those continents. Our findings demonstrate the importance of defining the spatiotemporal context of genetic ancestry when describing human genetic variation and caution against the oversimplified interpretations of genetic data prevalent in contemporary discussions of race and ancestry.
Functional genomics in malaria unlocks comparative biology across the family tree.Functional genomics in malaria unlocks comparative biology across the family tree.
The origins and prehistory of domestic sheep () are incompletely understood; to address this, we generated data from 118 ancient genomes spanning 12,000 years sampled from across Eurasia. Genomes from Central Türkiye ~80...The origins and prehistory of domestic sheep () are incompletely understood; to address this, we generated data from 118 ancient genomes spanning 12,000 years sampled from across Eurasia. Genomes from Central Türkiye ~8000 BCE are genetically proximal to the domestic origins of sheep but do not fully explain the ancestry of later populations, suggesting a mosaic of wild ancestries. Genomic signatures indicate selection by ancient herders for pigmentation patterns, hornedness, and growth rate. Although the first European sheep flocks derive from Türkiye, in a notable parallel with ancient human genome discoveries, we detected a major influx of Western steppe-related ancestry in the Bronze Age.
Genomes contain mosaics of discordant evolutionary histories, challenging the accurate inference of the tree of life. Although genome-wide data are routinely used for discordance-aware phylogenomic analyses, because of m...Genomes contain mosaics of discordant evolutionary histories, challenging the accurate inference of the tree of life. Although genome-wide data are routinely used for discordance-aware phylogenomic analyses, because of modeling and scalability limitations, the current practice leaves out large chunks of genomes. As more high-quality genomes become available, we urgently need discordance-aware methods to infer the tree directly from a multiple genome alignment. In this study, we introduce Coalescence-Aware Alignment-Based Species Tree Estimator (CASTER), a theoretically justified site-based method that eliminates the need to predefine recombination-free loci. CASTER is scalable to hundreds of mammalian whole genomes. We demonstrate the accuracy and scalability of CASTER in simulations that include recombination and apply CASTER to several biological datasets, showing that its per-site scores can reveal both biological and artifactual patterns of discordance across the genome.
Climate change may be driving an expansion of Valley fever, a deadly fungal infection spread by airborne spores.Climate change may be driving an expansion of Valley fever, a deadly fungal infection spread by airborne spores.
Protein phosphorylation signaling networks have a central role in how cells sense and respond to their environment. We engineered artificial phosphorylation networks in which reversible enzymatic phosphorylation cycles w...Protein phosphorylation signaling networks have a central role in how cells sense and respond to their environment. We engineered artificial phosphorylation networks in which reversible enzymatic phosphorylation cycles were assembled from modular protein domain parts and wired together to create synthetic phosphorylation circuits in human cells. Our design scheme enabled model-guided tuning of circuit function and the ability to make diverse network connections; synthetic phosphorylation circuits can be coupled to upstream cell surface receptors to enable fast-timescale sensing of extracellular ligands, and downstream connections can regulate gene expression. We engineered cell-based cytokine controllers that dynamically sense and suppress activated T cells. Our work introduces a generalizable approach that allows the design of signaling circuits that enable user-defined sense-and-respond function for diverse biosensing and therapeutic applications.
Adamala KP, Agashe D, Belkaid Y
… +35 more, Bittencourt DMC, Cai Y, Chang MW, Chen IA, Church GM, Cooper VS, Davis MM, Devaraj NK, Endy D, Esvelt KM, Glass JI, Hand TW, Inglesby TV, Isaacs FJ, James WG, Jones JDG, Kay MS, Lenski RE, Liu C, Medzhitov R, Nicotra ML, Oehm SB, Pannu J, Relman DA, Schwille P, Smith JA, Suga H, Szostak JW, Talbot NJ, Tiedje JM, Venter JC, Winter G, Zhang W, Zhu X, Zuber MT