Science Advances

The bodies of pterosaurs, the first flying vertebrates, are covered with integumentary filaments (pycnofibres) thought to be homologous to feathers in dinosaurs, but their coloration remains unknown. Here, we report a layered internal arrangement of melanosomes containing a photonic nanostructure within the monofilaments in a previously undescribed specimen of tapejarid pterosaur Sinopterus dongi from the Early Cretaceous Jehol Biota. Optical simulations showed that this structure reflects green to magenta iridescent coloration, confirming the presence of melanosome-based iridescent coloration previously thought to be unique to birds. This finding deepens our understanding of structure/color gamut relationships in amniotes, while supporting further shared characteristics associated with derived genetic and regulatory shifts in archosaurs.

AbstractBears exhibit an unusual form of hibernation in which core body temperature remains relatively high despite profound suppression of whole-body metabolism. How such a warm yet hypometabolic state is achieved remains poorly understood. Here, through integrative analysis of 238 RNA-seq datasets spanning seven species, we identify transmembrane protein 41B (TMEM41B) as an evolutionarily conserved factor associated with thermogenic capacity. Loss of Tmem41b in mice and Drosophila results in severe cold intolerance, whereas its overexpression enhances thermogenic performance, supporting a conserved role in heat production. Comparative genomic analyses reveal a bear-specific 51-amino acid N-terminal extension in TMEM41B, arising from a 5' untranslated region mutation that converts a premature stop codon into coding sequence. Interactome profiling indicates that this bear-specific isoform differs from the canonical TMEM41B in its protein interaction landscape, including reduced association with components of mitochondria-associated endoplasmic reticulum membranes such as voltage-dependent anion-selective channel protein 1 (VDAC1). Consistent with this altered interaction profile, the extended isoform is associated with reduced mitochondrial oxidative activity. Functional analyses further suggest that the 51- amino acid extension modulates multiple cellular programs, including suppression of oxidative phosphorylation and myogenic differentiation alongside activation of osteogenic pathways, collectively biasing cells toward a hypometabolic state. Notably, expression of the polar bear TMEM41B isoform in mice induces a torpor-like phenotype under fasting conditions. Together, these findings identify TMEM41B as a conserved regulator of thermogenic capacity and suggest that evolutionary modification of its N terminus may contribute to metabolic suppression and energy conservation during bear hibernation.

The brain relies on a range of nutrients for optimal functioning. However, the causal nature between dietary components and human intelligence are still unclear. This study integrates Mendelian randomization (MR) and genome-wide associations analyses to investigate the relationships. The results show that cheese exerts the most remarkable genetic correlation and causal association with cognition-related traits. We conduct a large-scale meta-analysis of genome-wide associations studies (GWAS) consisting of over 800,000 participants and discover 71 genetic determinants for cheese consumption. Additional MR using the GWAS results recovers the causal effects of cheese on all the cognition-related traits, and also reveals its effects on education, psychological states and gene expressions in multiple brain tissues. Additionally, knockout mouse models and pathway enrichment analysis indicate that the loci mapped genes are involved in cognitive functions and brain characteristics. In conclusion, our comprehensive analysis supports the potential benefits of cheese consumption on human intelligence.

AO_SCPLOWBSTRACTC_SCPLOWThe iridescent colors of birds originate in nanoscale feather structures that interact with light. Although the physical principles governing avian iridescence are well-established, the molecular mechanisms assembling these nanostructures into photonic materials remain unknown. Here, we investigate the genetic and developmental basis of iridescence by analyzing mutations from peafowl domestication and color variation in wild birds. We show that melanogenesis governs diverse geometric aspects of feather photonic nanostructures, enabling gains, shifts, and losses in iridescence. Mutations altering melanin composition collapse multilayered photonic systems and yield non-iridescent tissues, while alterations to melanosome abundance, elongation, or deposition timing generate multilayer architectures of variable periodicity and striking color differences. Notably, transitions from non-iridescent to iridescent plumage can arise from single-nucleotide mutations in melanogenic genes, revealing that minimal genetic change can prompt feathers to organize photonic structures. These results demonstrate that the nanoscale order underlying iridescence is developmentally plastic, emerging from physicochemical self-assembly responsive to the biochemical environment rather than from genetically encoded spatial cues. Single-cell transcriptomes from wild species further uncovered extensive melanocyte-centered regulatory rewiring associated with iridescence. Our findings identify melanogenesis as a key pathway for evolving structural coloration and illustrate how genetic programs harness self-organizing processes to generate biological diversity.

Natural light is severely affected by human impact on Earth, yet little is known about the roles light receptors have outside vision and rhythmic processes. Here we show that loss-of-function of the light-receptive cryptochrome (l-cry) in marine bristleworms significantly increases lifespan and adult size, similarly to wild-types reared in constant darkness. Quantitative transcriptomics revealed hormonal players crucial for invertebrate and vertebrate sexual development and reproduction affected in l-cry mutants. These include nr0b1/2, ortholog of dax-1 (nr0b1) and shp (nr0b2), long considered vertebrate novelties. Depending on moon-phase, nr0b1/2 is up- or down-regulated in l-cry mutants. Matching the complex regulation, loss of nr0b1/2 function partially recapitulates l-cry phenotypes. Molecularly, Platynereis Nr0b1/2 affects steroidogenic and other endocrine pathways, nuclear receptor signaling, and transcription factor orthologs, involved in sexual developmental, reproductive, and timing processes in other organisms. Thus, our study reveals profound effects of light on adult animal life-time, likely at least in part by conserved endocrine pathways involved in sexual maturation and reproduction in annelids and vertebrates.

Sponges (phylum Porifera) have been essential to marine ecosystems for over 600 million years, contributing to nutrient cycling, reef building, and ecological stability. Despite their evolutionary importance, the drivers of their diversity dynamics remain poorly understood. This study investigates the diversification patterns of Demospongiae, the largest class of sponges with a well-documented fossil record throughout the Phanerozoic Eon (541-0 Ma). Using fossil occurrence data and a Bayesian framework, we modeled origination and extinction rates to understand their evolutionary history. Our findings reveal key extinction events, including three previously unrecognized events in the Cambrian, Late Silurian, and Late Jurassic, alongside known events such as the Permian-Triassic and Triassic-Jurassic extinctions. Notably, there was no statistical evidence for mass extinction during the Late Ordovician or Late Devonian. Additionally, Demosponges underwent a significant decline prior to the Cretaceous-Paleogene extinction. To explore abiotic influences, we applied the Multivariate Birth-Death (MBD) model across all extinction events. This analysis identified correlations between major speciation and extinction events and key variables, including temperature, continental fragmentation, oxygen levels, and sea level, as well as geochemical proxies such as sulfur and strontium, which may reflect underlying drivers like anoxia, weathering, or tectonic activity. Temperature and oxygen levels, in particular, correlated with speciation and extinction during the Permian-Triassic extinction. These findings underscore the role of environmental fluctuations in shaping demosponge diversity and highlight the complex interplay between changes in abiotic factors and sponge evolution. Our work provides critical insights into the factors driving sponge biodiversity and offers perspectives on how modern sponges might respond to ongoing climate change. Significance StatementSponges are ancient and ecologically pivotal marine organisms that have persisted through Earths major environmental upheavals. Despite their resilience, the mechanisms driving their evolutionary responses to past climate shifts remain unclear. By leveraging the fossil record of Demospongiae, this study identifies previously unrecognized extinction events and elucidates how abiotic factors, including temperature and oxygen levels, shaped their diversity during these crises. These findings enhance our understanding of sponge evolutionary dynamics and resilience, offering critical insights into the vulnerability of marine ecosystems under current and future climate change scenarios.

Here we reveal an unanticipated role of the blood-brain-barrier (BBB) in regulating complex social behavior in ants. Using scRNA-seq we find localization in the BBB of a key hormone-degrading enzyme called Juvenile hormone esterase (Jhe), and we show that this localization governs the level of Juvenile Hormone (JH3) entering the brain. Manipulation of the Jhe level reprograms the brain transcriptome between ant castes. While ant Jhe is retained and functions intracellularly within the BBB, we show that Drosophila Jhe is naturally extracellular. Heterologous expression of ant Jhe into the Drosophila BBB alters behavior in fly to mimic what is seen in ant. Most strikingly, manipulation of Jhe levels in ant reprograms complex behavior between worker castes. Our study thus uncovers a novel, potentially conserved role of the BBB serving as a molecular gatekeeper for a neurohormonal pathway that regulates social behavior.

An animal adapts its motor behavior to navigate the external environment. This adaptation depends on proprioception, which provides feedback on an animals body postures. How proprioception mechanisms interact with motor circuits and contribute to locomotor adaptation remains unclear. Here we describe and characterize proprioception-mediated homeostatic control of undulatory movement in the roundworm Caenorhabditis elegans. We found the worm responds to optogenetically or mechanically induced decreases in midbody bending amplitude by increasing its anterior amplitude. Conversely, it responds to increased midbody amplitude by decreasing the anterior amplitude. Using genetics, microfluidic and optogenetic perturbation response analyses, and optical neurophysiology, we elucidated the neural circuit underlying this compensatory postural response. The dopaminergic PDE neurons proprioceptively sense midbody bending and signal to AVK interneurons via the D2-like dopamine receptor DOP-3. The FMRFamide-like neuropeptide FLP-1, released by AVK, regulates SMB head motor neurons to modulate anterior bending. We propose that this homeostatic behavioral control optimizes locomotor efficiency. Our findings demonstrate a mechanism in which proprioception works with dopamine and neuropeptide signaling to mediate motor control, a motif that may be conserved in other animals.

The hypothesis of the Great Evolutionary Faunas is a foundational concept of macroevolutionary research postulating that three global mega-assemblages have dominated Phanerozoic oceans following abrupt biotic transitions. Empirical estimates of this large-scale pattern depend on several methodological decisions and are based on approaches unable to capture multiscale dynamics of the underlying Earth-Life System. Combining a multilayer network representation of fossil data with a multilevel clustering that eliminates the subjectivity inherent to distance-based approaches, we demonstrate that Phanerozoic oceans sequentially harbored four global benthic mega-assemblages. Shifts in dominance patterns among these global marine mega-assemblages are abrupt (end-Cambrian 494 Ma; end-Permian 252 Ma) or protracted (mid-Cretaceous 129 Ma), and represent the three major biotic transitions in Earths history. This finding suggests that the mid-Cretaceous radiation of the so-called Modern evolutionary Fauna, concurrent with gradual ecological changes associated with the Mesozoic Marine Revolution, triggered a biotic transition comparably to the transition following the largest extinction event in the Phanerozoic. Overall, our study supports the notion that both long-term ecological changes and major geological events have played crucial roles in shaping mega-assemblages that dominated Phanerozoic oceans.

Transcription factors (TFs) are traditionally depicted as monomeric, or oligomeric, units that recognize and bind specific DNA sequences to regulate transcription. Emerging evidence suggests that many TFs can undergo liquid phase separation, resulting in condensates that bind DNA through a different mechanism. For the Auxin Response Factors (ARFs), canonical plant TFs, evidence for both scenarios exists. But which of these scenarios is operational in the plant nucleus is unclear. Here, we demonstrate using MpARF2 of Marchantia polymorpha that a third scenario is operational: MpARF2 forms nanoscopic clusters under physiological conditions. Nanoclusters combine DNA-binding features that cannot be accessed by the other two scenarios: high-affinity, switch-like, and sequence-specific. Our results suggest nanoclustering as a mechanism that equips TFs with the DNA-binding properties necessary for transcriptional regulation. TeaserTranscription factor nanoclusters balance the DNA-binding trade-off between weakly binding oligomers and nonspecific condensates.

Despite the accumulating evidence that increased consumption of ultra-processed food has adverse health implications, it remains difficult to decide what constitutes processed food. Indeed, the current processing-based classification of food has limited coverage and does not differentiate between degrees of processing, hindering consumer choices and slowing research on the health implications of processed food. Here we introduce a machine learning algorithm that accurately predicts the degree of processing for any food, indicating that over 73% of the U.S. food supply is ultra-processed. We show that the increased reliance of an individuals diet on ultra-processed food correlates with higher risk of metabolic syndrome, diabetes, angina, elevated blood pressure and biological age, and reduces the bio-availability of vitamins. Finally, we find that replacing foods with less processed alternatives can significantly reduce the health implications of ultra-processed food, suggesting that access to information on the degree of processing, currently unavailable to consumers, could improve population health.

Grass pollen is largely overlooked in investigating grassland evolution because the pollen of most species cannot be differentiated using traditional optical microscopy. However, deep learning can quantify small variations in pollen morphology visible under superresolution microscopy. We use the abstract features output by deep learning to estimate the taxonomic diversity and physiology of fossil grass pollen assemblages. Using a semi-supervised learning strategy, we trained convolutional neural networks (CNNs) on superresolution pollen images of modern grasses and unlabeled fossil Poaceae. Our models captured features that reflected both the taxonomic diversity of grass communities along an elevational gradient and morphological differences between C3 and C4 species. We applied our trained models to fossil grass pollen assemblages from a 25,000-year lake-sediment record from eastern equatorial Africa (Mt. Kenya) and correlated past shifts in grass diversity with atmospheric CO2 concentration and proxy records of local temperature, precipitation, and fire occurrence. We quantified changes in grass diversity using morphological variability of fossil pollen assemblages, approximated by the Shannon entropy of CNN features. Our data show that grassland species diversity was strongly reduced between 21,500 and 16,000 years ago, coincident with most severe regional cooling during the last ice age. C3:C4 ratios reconstructed using a gradient-boosted decision tree classifier infer a gradual decrease in C4 grasses since the late-glacial to Holocene transition, associated with decreasing fire activity and elevated temperatures. Our results demonstrate that CNN features of pollen morphology can advance palynological analysis, enabling robust estimation of grass diversity and C3:C4 ratio in ancient grassland ecosystems. SignificanceAlthough the pollen of most grass species are morphologically indistinguishable using traditional optical microscopy, we show that they can be differentiated through deep learning analyses of superresolution images. Abstracted morphological features derived from convolutional neural networks can be used to quantify the biological and physiological diversity of grass pollen assemblages, without a priori knowledge of the species present, and used to reconstruct past changes in the taxonomic diversity and relative abundance of C4 grasses in ancient grasslands. This approach unlocks ecological information previously unattainable from the fossil pollen record and demonstrates that deep learning can solve some of the most intractable identification problems in the reconstruction of past vegetation dynamics.

The electric excitability of muscle, heart and brain tissue relies on the precise interplay of Na+- and K+-selective ion channels. The involved ion fluxes are controlled in optogenetic studies using light-gated channelrhodopsins (ChRs). While non-selective cation-conducting ChRs are well-established for excitation, K+-selective ChRs (KCRs) for efficient inhibition have only recently come into reach. Here, we report the molecular analysis of recently discovered KCRs from the stramenopile Hyphochytrium catenoides and identify a novel type of hydrophobic K+-selectivity filter. Next, we demonstrate that the KCR signature motif is conserved in related stramenopile ChRs. Among them, WiChR from Wobblia lunata features an unmatched 80-fold preference for K+ over Na+, stable photocurrents under continuous illumination and a prolonged open state lifetime. Well expressed in neurons, WiChR allows two-photon inhibition at low irradiance and reduced tissue heating,_recommending WiChR as the long-awaited efficient and versatile optogenetic inhibitor.

The kidney develops through branching of progressively crowded ureteric bud (UB) tubules at the organ surface. The elongating tubule tips are surrounded by traveling cap mesenchyme niches consisting of nephron progenitors and separated by stromal boundaries. Dynamic interactions between these tissues coordinate a balance between UB tip branching, elongation, and nephron induction that sets nephron numbers for life, impacting the likelihood of adult disease. Such a crowded tissue environment could place geometric limits on the number of niches that can be formed while maintaining mechanical integrity of the tissue. Since space is at a premium, crowding could also force a given niche to prioritize between nephron formation or UB branching differently depending on its spatial context. Here we study the geometric and mechanical consequences of tubule tip crowding at the embryonic kidney surface. Organ curvature reduces and tubule tip domain niches pack more closely over developmental time. These together create a semi-crystalline geometry of tips at the kidney surface and a rigidity transition to more solid-like tissue properties at later developmental stages. To infer mechanical dynamics over the branching timescale, we define a new method to infer tip domain ages relative to their most recent branch events from fixed kidneys. We find that new tip domains overcome mechanical resistance as they branch and displace close-packed neighbors, transiently increasing mechanical stress in the niche. Ongoing efforts to understand geometric and mechanical effects on niche regulation will clarify variation in kidney tissue composition and advance engineering control strategies for synthetic regenerative tissues.

The rise of Neogene herbivores with high-crowned (hypsodont) molar teeth has been viewed as a mostly predictable response to abrasive grazing diets. Using kangaroos, an isolated marsupial radiation, we show that the ancestral vertical slicing function of grazing kangaroo molars prompted heavy investment from the late Miocene in thickened enamel, rather than hypsodonty. Grazing kangaroo enamel thickness overlaps some robust hominins, evincing an eclectic, thick-enamelled grazer guild. The success of vertically-chewing marsupials contrasts with their placental counterparts, which were overwhelmingly replaced by transversely-chewing ungulates. This inversion is explained by the pre-grassland extinction of most transversely-chewing marsupials, and the crucial advent of thick enamel. These results challenge the determinism of the browser-grazer transition, and implicate extinction, and ensuing innovation, as causes of unpredictability in evolution.

A large body of work suggests that biomolecular condensates ensuing from liquid-liquid phase separation mature into various material states. How this aging process is controlled and if the naive and mature phases can have differential functions is currently unknown. Using Caenorhabditis elegans as a model, we show that MEC-2 Stomatin undergoes a rigidity phase transition during maturation from fluid to viscoelastic, glass-like condensates that facilitate either transport or mechanotransduction. This switch is promoted by the SH3 domain of UNC-89/Titin/Obscurin through a direct interaction with MEC-2 and suggests a physiological role for a percolation transition in force transmission during body wall touch. Together, our data demonstrate a novel function for rigidity maturation during mechanotransduction and a previously unidentified role for Titin homologs in neurons.

Vampire bats are the only tetrapods that feed exclusively on blood. To uncover the molecular basis of this extreme dietary specialization, we generated six new reference genomes, including genomes of all three vampire bat species, and integrated comparative analyses of gene sequence evolution (selection signatures, duplications, and losses) with transcriptomic data from six major organs to identify shifts in gene expression. Our integrative analyses reveal sequence or expression changes in 150 genes that illuminate the genetic mechanisms underlying sanguivory. Through comparative analyses and experiments, we show that the enlarged vampire bat stomach has increased connective tissue content enabling extreme expansion, is pH-neutral, and exhibits reduced mucus production, together providing molecular insights into its shift from a digestive to an absorptive organ for water, electrolytes, and vitamins. We further uncover pathway-level molecular changes underlying altered gastrointestinal motility; trypsin-dependent protein digestion; upregulated amino acid catabolism with key aspects diverging from other mammals; impaired dietary fat digestion counterbalanced by increased fatty acid synthesis; defective sugar metabolism and natural insulin deficiency; enhanced heme iron absorption; and adult splenic erythropoiesis. Together, these findings reveal the molecular adaptations that enable one of the most extreme dietary transitions among vertebrates.

X chromosome inactivation (X-inactivation) is generally regarded as a dosage-compensation mechanism restricted to female mammals. Here we show that BMP signaling induces X-inactivation through upregulation of Xist and promotes chondrogenesis in both sexes. Remarkably, augmented BMP signaling induced ectopic X-inactivation: transiently inactivating both X chromosomes in females and one in males in a tissue-specific manner. In cranial neural crest cells, ectopic X-inactivation suppressed X-linked gene Tmsb4x, leading to ectopic cartilage formation. Genetic reduction of Xist or pharmacological restoration of the Tmsb4x product suppressed this phenotype. Moreover, we identified ectopic X-inactivation in SOX9-positive chondroprogenitors during wild-type forelimb development in both sexes. Inhibition of X-inactivation disrupts proximodistal limb patterning ex vivo. These findings establish X-inactivation as a signaling-dependent developmental mechanism linking chromosome-scale gene alterations to skeletal fate specification.

Understanding the fitness landscape of viral mutations is crucial for uncovering the evolutionary mechanisms contributing to pandemic behavior. Here, we apply a Gaussian process regression (GPR) based machine learning approach that generates spatial covariance (SCV) relationships to construct stability fitness landscapes for the RNA-dependent RNA polymerase (RdRp) of SARS- CoV-2. GPR generated fitness scores capture on a residue-by-residue basis a covariant fitness cluster centered at the C487-H642-C645-C646 Zn2+ binding motif that iteratively evolves since the early phase pandemic. In the Alpha and Delta variant of concern (VOC), multi-residue SCV interactions in the NiRAN domain form a second fitness cluster contributing to spread. Strikingly, a novel third fitness cluster harboring a Delta VOC basal mutation G671S augments RdRp structural plasticity to potentially promote rapid spread through viral load. GPR principled SCV provides a generalizable tool to mechanistically understand evolution of viral genomes at atomic resolution contributing to fitness at the pathogen-host interface.

As one of the first domestic livestock species, sheep have played a fundamental role in human societies since the Neolithic. However, their demographic history remains poorly understood. To shed light on the demographic dynamics of sheep at the western edge of the Mediterranean, we sequenced 22 ancient sheep genomes from Iberia (dating from 7, 270 to 1, 615 calBP, sequenced up to 8.74 x coverage) along with one modern European mouflon from Corsica. We provide evidence for an initial maritime introduction into Iberia, and show that European mouflons are descendants of feralized Neolithic sheep. Further-more, we identify a secondary influx of "Eastern" genetic ancestry coinciding with the arrival of human Steppe ancestry in Iberia - an event that likely aligns with the spread of woolly sheep across Europe. A third population expansion is observed during the Roman period, a time when historical sources reference the trade of fine-wool sheep. This Roman-era expansion appears to have significantly influenced the genetic makeup of modern European sheep, contributing to the development of popular modern-day breeds such as Merino. In addition to these major events, we see indications of additional, minor episodes of prehistoric gene flow into the Iberian population, suggesting that western European sheep experienced more dynamic demographic changes than other domestic animals, humans, or sheep populations elsewhere. Together, these results highlight the dynamic history of Iberian sheep populations and demonstrate how human cultural and demographic shifts have left their hoofprints in the sheep gene pool, marking them as a valuable proxy for understanding the human past.