PLOS Biology

Parental care is widespread across the animal kingdom and plays a critical role in offspring development. Yet, its broader genetic and evolutionary impacts remain underexplored. Here, using the biparental burying beetle Nicrophorus vespilloides as a model, we show that parental care acts as a genetic capacitor: it allows genetic variation to accumulate while care is present and releases it when care is disrupted. By experimentally manipulating care, we demonstrate that parental care suppresses genetic variation associated with offspring body size, which is released when care is lost. To investigate the underlying molecular mechanisms, we generate a chromosome-scale genome assembly for N. vespilloides, alongside a single-nucleus gene expression atlas and epigenomic datasets from larvae reared with and without parental care. We find that the loss of parental care induces molecular stress, disrupting the expression of the protein chaperone Hsp83, which is a well-known molecular capacitor, alongside other putative mRNA chaperones. Moreover, our results suggest that parental care buffers development by maintaining an open, responsive chromatin landscape and redundant gene regulatory interactions. Overall, our work reveals that parental care shapes the storage, expression and release of genetic variation with broad implications for adaptation and evolution.

Accurate localization of anatomical landmarks is a foundational skill in anatomy and imaging that is often taught informally through expert mentorship, requiring access to data and desktop software. There is no openly accessible, interactive resource that teaches neuroanatomy with quantitative feedback. We present the AFIDs-Validator (validator.afids.io), an open-access, browser-based platform that pairs guided instruction with quantitative assessment. The platform combines (1) a learning mode in which a language-model neuroanatomy tutor operates inside an MRI viewer, giving anatomy-first instruction that responds to the learner's current image slice, orientation, and cursor position; and (2) a validation engine that accepts a learner's landmark file and returns per-landmark Euclidean error against expert-annotated references spanning 21 brain templates. To make the feedback interpretable, we analyzed 15,000 landmark annotations across 132 human subjects and found that landmark difficulty varies fourfold (median error ranged from 0.37 mm at the anterior commissure to 1.50 mm at the temporal horns) with heavy-tailed distributions at every landmark. These distributions are compiled into per-landmark reliability priors, so learners are scored against the empirical spread of trained raters rather than an arbitrary threshold, and difficult landmarks are not mistaken for poor performance. The AFIDs-Validator requires no installation, licensed software, or local data, and all code, reference data, and tutor design are openly released.

Research on butterflies has uncovered a conserved "toolkit" of genes for color pattern development and evolution. One of these genes is optix, a homeobox transcription factor that regulates ommochrome and melanin pigmentation, as well as structural coloration, in nymphalid butterflies. It remains unclear, however, whether optix plays any roles in color patterning outside of the Nymphalidae. We used CRISPR-Cas9 to disrupt optix in the tobacco hornwormmoth Manduca sexta and observed a dramatic abdominal pigmentation phenotype, where orange pigmentation was replaced by black eumelanin. Chemical assays suggest that the orange pigment is not an ommochrome, indicating that optix modulates an alternative, uncharacterized pigment pathway in M. sexta. RNA-seq and chemical analyses of orange and black abdominal scales lead us to speculate that the orange pigment may be a type of melanin, perhaps N-{beta}-alanyldopamine (NBAD) sclerotin. Our results suggest that optix plays a deeply ancestral role in pigment regulation in Lepidoptera, and demonstrates evolutionary flexibility in how it interfaces with pigment chemistry across moths and butterflies.

Open data sharing is increasingly mandated by research funders, journals, and institutions, yet large-scale compliance measurement remains challenging. We analyzed 951,949 open access biomedical research articles published between January 2024 and June 2025 using a dual-source pipeline: PDF-based text extraction (MinerU) where PDFs were available and PMC XML otherwise, followed by algorithmic detection of data sharing statements (oddpub v7.2.3), enriched with funder, journal, and institutional metadata from OpenAlex. The corpus included 294,172 PDF-covered articles (30.9%) and 657,777 XML-only articles (69.1%). We found an over-all open data rate of 8.7%, rising to 11.7% among funder-linked articles (those with at least one funder identified in the metadata). Rates varied more than tenfold across the research ecosystem: leading major funders reached observed open data rates of 20-24%, while top journals reached observed rates of 70-86%, with corrected estimates as high as 92.9% (Nature Genetics) after adjusting for XML-only coverage limitations. PDF-based detection identified approximately 52% more data sharing statements than XML-based methods on the same articles. These observed rates differ markedly across funders and journals, and current overall sharing remains far below universal compliance. These patterns provide an empirical baseline against which future policy changes can be measured. An interactive dashboard at https://www.opensciencemetrics.org enables stakeholders to explore and benchmark these results.

Collateral sensitivity (CS) - resistance to one antibiotic inducing hypersensitivity to another - offers an evolutionary trap for multidrug-resistant pathogens. A strongly connected component (SCC) in the directed CS graph is a closed cycle in which every drug is reachable from every other. Prior evidence for CS SCCs is exclusively in vitro. We mined 104,337 susceptibility records from BV-BRC spanning four WHO critical-priority pathogens (Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa; 18,821 isolates), using Fisher's exact tests with Benjamini-Hochberg FDR correction, Tarjan's algorithm, and permutation testing (n = 1,000). Two species yielded qualifying SCCs. In K. pneumoniae (4,286 isolates), a 3-node SCC - imipenem, meropenem, tetracycline - was detected (empirical p = 0.001); both carbapenem-tetracycline edges are bidirectional (OR = 1.81-1.82, q < 0.002, n > 850 per edge). In E. coli (6,720 isolates), a bidirectional 2-node SCC links colistin and cefotaxime (OR = 10.13, 95% CI 2.82-46.12, q = 0.042, n = 87; permutation p = 0.008); with a fragility index of 1, we report it as a hypothesis, not an established effect size. The carbapenem signal is tetracycline-specific: tigecycline shows co-resistance (OR < 0.35), as its distinct RamA/AcrAB-TolC mechanism predicts. ORs of 2.2-2.7 persisted across independent year bands (2009-2014). S. aureus returned no qualifying SCC, but that null is power-limited: only 8% of testable pairs could detect the K. pneumoniae effect size. Prior clinical analyses characterised pairwise and three-way collateral effects; to our knowledge these are the first closed CS cycles identified in clinical surveillance data, motivating experimental follow-up.

Although it is well established that certain stages of development are molecularly more conserved than others, the reasons for this phenomenon remain largely unknown. We study molecular conservation in the development of an organ, the molar, by comparing the temporal profiles of expression in mice and hamsters. We find that the cause of conservation of expression and of coding sequences changes over molar development. Gene expression levels display a classical increase of divergence as development progresses. In terms of genes expressed, the composition of early and late stages is better conserved and enriched in pleiotropic genes, yet each stage mobilizes different sets of pleiotropic genes, cell division for bud growth and secretion for tooth mineralization. Moreover similar patterns of higher divergence of gene sets and of coding sequences at mid development, are caused by different biological phenomena, in that case heterochronies and blood colonisation respectively. In conclusion, the patterns of molecular conservation in developing molars are shaped by a combination of processes intrinsic to the teeth, and by negative and positive selection on functions which are mostly extrinsic to the teeth. This is likely translatable to explain molecular conservation patterns in many other biological systems. AUTHOR SUMMARYFor species to evolve different adaptations to different life styles, their anatomy has to evolve correspondingly. This in turn implies evolution of the embryonic development of anatomical structures. Notably, tooth shape can evolve rapidly as an adaptation to different diets. Mice and hamsters are closely related rodents who yet differ in the shape of their molars, and thus in their development. In this study, we investigated why the genes active in molar development are more or less similar between the two species from early tooth bud to fully formed embryo molar. We found that early and late molar development were slow evolving, while mid-development was evolving faster. But surprisingly, this was in part due not to tooth evolution, but to the involvement of genes which are active in other processes in the body. For example an influx of immune cells also brings fast evolving immune genes. This helps us understand better the complexity of causes of apparently simple evolutionary patterns.

Preprints now disseminate a large share of biomedical research before peer review. Because they have not yet passed peer review, some scientists regard preprint claims as unverified or potentially unreliable, yet how much those claims change before publication has so far been quantified only in smaller cohorts, with results that vary by field and topic. Here, we compiled every bioRxiv preprint posted between 2018 and 2025 that we could match by DOI to a peer-reviewed published version, yielding 72,644 preprint-publication pairs. Using a large language model (Claude Sonnet 4.6), we parsed every preprint-publication abstract pair into one primary and two secondary claims, and classified each pair for content change (unchanged, minor, major) and hedging shift (more cautious, more confident, unchanged). On a validation subsample, the model agreed with two independent domain experts about as well as the experts agreed with each other (Cohens kappa 0.63 to 0.66). The primary claim was unchanged in 39.9% of abstracts, minorly revised in 50.0%, and substantially revised in only 10.2%. Hedging shifts were uncommon and asymmetric, with twice as many claims becoming more cautious as more confident (8.4% vs 4.2%). Major revisions were more frequent after long peer review (14.1% in the slowest versus 7.0% in the fastest tertile of review time) and declined over the study period (17.0% in 2019 to 5.7% in 2024). Over the same period, biomedical papers that were never posted as preprints were retracted at roughly twice the rate of those that were. Together, these data show that the move from preprint to peer-reviewed publication leaves the central claims of most biomedical abstracts intact, indicating that preprints are a reliable source of biomedical research.

Gene loss is a widespread phenomenon that shapes genome evolution, yet the factors determining why certain genes are repeatedly lost while other functionally related genes are retained remain poorly understood. We addressed this question using the peptide-processing metallocarboxypeptidases carboxypeptidase E (CPE) and carboxypeptidase D (CPD), conserved paralogues that are essential for neuropeptide maturation but strikingly differ in their evolutionary fate: the cpe gene has been independently lost in two major insect lineages, whereas cpd/svr has been universally retained. Combining gene phylogenetic analyses and functional genetics in the beetle Tribolium castaneum, and cross-species rescue experiments in the fly Drosophila melanogaster, we show that CPE and CPD retained partially interchangeable enzymatic functions despite considerable differences in structure, organismal importance and expression. Contrary to expectations, cpe proved more critical than cpd/svr for survival and developmental robustness in Tribolium, while simultaneous RNAi-mediated downregulation of both genes caused complete larval lethality, demonstrating only partial functional redundancy. Moreover, beetle CPE partially rescued the lethal loss of Drosophila CPD, establishing conserved molecular interchangeability across [~]300 million years of insect evolution. Gene phylogenetic analyses further indicate that bilaterian CPE originated through duplication of the second catalytic domain of an ancestral CPD. Together, our results demonstrate that repeated loss of insect cpe cannot be explained by reduced functional importance. Instead, we propose that the structural versatility, broader tissue distribution and multifunctionality of CPD, including its multidomain architecture and splice isoforms, enabled compensation for CPE after gene loss, thereby shaping long-term patterns of gene retention and loss during insect evolution.

Major transitions in evolution are associated with the loss of independent reproduction by formerly autonomous units. Termites provide a powerful system for studying this process because they exhibit diverse social systems in which worker developmental and reproductive potential declines with increasing colony-level organismality. However, the evolutionary sequence and developmental genetic basis of these transitions remain unresolved. Here, using comparative developmental transcriptomics across seven termite species that differ in workers' reproductive potential, we reconstructed the evolutionary history of termite social systems. We found that linear caste development, in which workers retain full reproductive potential, represents the ancestral state of termites. Bifurcated caste development, in which workers partially lose reproductive potential early in development, evolved independently multiple times, with two origins subsequently giving rise to superorganisms with unipotent, sterile workers. Ancestral gene regulatory network (GRN) reconstruction revealed that linear caste development evolved through retention of a juvenile-like worker state and co-option of a conserved developmental GRN characterizing hemimetabolous insect nymphal development, in which juvenile hormone, ecdysone and TGF-{beta} signaling pathways play central roles. The convergent evolution of bifurcated caste development repeatedly co-opted the GRN underlying linear caste development, heterochronically shifting its activity to earlier developmental stages. Finally, we found that the evolution of termite superorganisms involved somatization of the worker caste and co-option of a conserved endocrine GRN for terminal differentiation. Together, these findings uncovered repeated routes to reduced workers' reproductive potential through GRN co-option and highlight striking parallels between superorganism evolution in social insects and organismal evolution in metazoans.

Longitudinal animal experiments generate behavior that is individual, history-dependent, and sometimes affected by ordinary procedural irregularities, yet analyses commonly reduce such records to pooled averages or synchronous trial-level explanations. We introduce history-structured forecasting as an auditable framework for determining whether an animals own preceding behavior carries predictive information beyond current-trial context. We applied the framework to 213,990 events from rats performing an auditory duration-discrimination task, using leakage-safe chronological forward-chaining, explicit trivial baselines, and controls that reset, exchange, or disrupt behavioral history. A transparent gradient-boosted model achieved 51.7% four-class accuracy, exceeding last-action persistence (40.9%) and prefix-derived subject-modal prediction (37.2%); decline-class AUPRC was 0.525 against a prevalence baseline of 0.303. Validation showed that the predictive advantage depended predominantly on each animals short-range sequential action history rather than group-level history, subject identity alone, or reward/correctness features, and strengthened on genuine choice trials. Forecasting remained informative across all 23 labeled animals, including six with recoverable records affected by incorrect training programming. These results revise the interpretation of rewarded give-up behavior while demonstrating how recoverable irregular records can be retained in transparent robustness analyses. History-structured forecasting offers a reusable open-science strategy for extracting reproducible evidence from imperfect longitudinal animal records without creating an artificially clean cohort.

The timing of the origins of the crown-group placental mammals has provided one of the classic battlefields in the long-running debate over when clades arise. Undoubted fossil crown-group placentals appear only in the Paleogene, but even so most molecular analyses, and many palaeontologists, have suggested their true origin is somewhere between 70-100 Ma. However, apart from the fact of the fossil record itself, there are several reasons to believe that the true origin is indeed post-Cretaceous, including consideration of the dynamics of stem and crown groups, which strongly favour crown-group origins to lie just after, and not just before, mass extinctions. Here we consider this "hard explosive" model in the light of the newly-developed "Covariant Evolutionary Tempo (CET)" model which allows diversification and molecular evolution rates to covary. It predicts "early bursts" in both lineage creation and molecular evolution at the base of major radiations which lead to highly unequally-sized clades; and an inheritance of rapid rates from this initial event by extant rapidly-evolving clades. We show that when the placentals are constrained to emerge after the K-Pg boundary, they indeed show elevated rates of both diversification and molecular evolution, which rapidly decline. Nevertheless, although elevated, these rates are comparable to the fastest rates seen in extant clades such as the rodents. In addition, the contiguous lineages leading from the origin to the rodents and other fast evolving clades also show elevated rates. These patterns suggest that not only is a Paleogene origin for the placental crown-group plausible, as fossil evidence suggests, but they also provide support for the CET model, which should be considered in other cases of pronounced fossil record/molecular clock mismatch.

Consciousness and cognition arise from the ongoing interactions between brain regions. Synchronous fluctuations of fMRI signals may indicate that two brain regions perform similar cognitive functions, but neural interactions are also constrained by anatomical connectivity and regions molecular, cytoarchitectonic, and metabolic profiles. Here we disentangle the respective contributions of ongoing cognition and multimodal neurobiological constraints in shaping functional connectivity. We jointly contextualise haemodynamic FC against eight distinct multimodal representations of the human connectome: (i) structural connectivity from diffusion tractography; (ii) spatial embedding; (iii) similarity of transcriptional profiles from gene expression; (iv) similarity of receptor profiles from Positron Emission Tomography; (v) laminar profile similarity from histology; (vi) correlated electrophysiological activity from magnetoencephalography; (vii) correlated metabolic activity from PET glucose uptake; (viii) coordinated activation across 123 cognitive operations from the NeuroSynth meta-analytic engine. We demonstrate that cognitive co-activation is the dominant predictor of inter-regional fMRI synchrony in the awake human brain, even when quantified using intracranial electrical stimulation. Crucially, this predominance of cognitive co-activation for shaping functional connectivity is systematically obliterated across five datasets of pharmacological and pathological perturbations of consciousness (chronic disorders of consciousness; anaesthesia with sevoflurane, propofol, or ketamine) when cognition is disconnected from the environment or altogether abolished. Altogether, we show that multimodal predictors of functional architecture shift away from cognitive co-activation and toward anatomicalmolecular constraints during pharmacological and pathological perturbations of consciousness.

Discrete voluntary movement depends on rapid changes in neural excitability across cortical and corticospinal circuits, yet how intrinsic movement-related neural states shape multi-level excitability remains unclear. Here, we combined individualized, state-targeted transcranial magnetic stimulation (TMS) with electroencephalography and electromyography recordings during visually cued finger movements to probe excitability across movement-related beta-band dynamics during two complementary experiments. Immediate transsynaptic cortical excitability closely tracked intrinsic beta dynamics, with attenuation of the second immediate TMS-evoked potential during beta desynchronization and recovery during the post-movement beta rebound. In contrast, corticospinal excitability showed the opposite pattern, with larger motor-evoked potentials during beta desynchronization and reduced responses during beta rebound. Together, these findings identify endogenous beta-state dynamics as a key regulator of movement-related cortical excitability and reveal a fundamental dissociation between how intrinsic brain activity tunes local cortical excitability and corticospinal output in humans.

Humans reliably associate certain speech-like sounds with visual shapes, most notably in the Bouba-Kiki Effect, where rounded and spiky shapes are matched with the sounds Bouba and Kiki, respectively. Although often linked to language and culture, evidence from preverbal infants and domestic chickens suggests that sound-shape correspondences may reflect an experience-independent perceptual bias. However, studies on great apes failed to detect such bias, leaving open the question on its phylogenetic origin. Using a free-choice task, we showed the Bouba-Kiki effect in nine macaques, thus suggesting that such correspondences represent a conserved feature of vertebrate perception that may have provided a scaffold for the later emergence of symbolic communication systems in our species.

Reproductive isolation is a central driver of speciation and can be reinforced by both innate mate preferences and mate preference learning. Pigmentation genes are strong candidates for pleiotropic effects on these processes because they shape visual traits used in mate choice and may also influence neural function, yet their role in learning is poorly understood. Here, we test whether the pigmentation gene yellow affects innate mate preference and aversive mate preference learning in female Bicyclus anynana, and whether these effects are associated with changes in brain dopamine levels. Using CRISPR-Cas9, we knocked out the yellow gene, developed a mutant line, and tested the mate preferences and mate preference learning ability of mutant females compared to wild-type (WT) females. We find that loss of yellow does not alter assortative mating based on pigmentation or disrupt innate visual or olfactory preferences. In contrast, loss of yellow does influence learning ability, as mutant females failed to modify mate preference following aversive premating experience, indicating an impairment in aversive learning. Despite yellows role in the melanin biosynthesis pathway, brain dopamine levels remain unchanged in mutant females relative to WT females. These findings identify yellow as a pleiotropic gene influencing both pigmentation and aversive mate preference learning, providing evidence that pigmentation genes can shape behavioral processes important for reproductive isolation and speciation. Significance statementPigmentation genes are best known for controlling color patterns, but they may also influence behavior through shared neural pathways. Here, we show that the pigmentation gene yellow is required for aversive mate preference learning in the butterfly Bicyclus anynana. Females lacking yellow retain normal innate visual and olfactory mate preferences but fail to learn to avoid previously unattractive mates. Surprisingly, this learning deficit is not associated with altered dopamine levels, suggesting that downstream neural signaling pathways are involved instead. These findings identify a gene that influences both pigmentation and learned mate preference, providing evidence that pigmentation genes can shape behavioral processes important for reproductive isolation and speciation.

Long considered a structure dedicated primarily to motor control, the cerebellum is now known to contain regions that respond selectively to language. However, how cerebellar language specialization emerges during development remains unknown. The prevailing proposal is that cerebellar functional specialization critically depends on inputs from the contralateral neocortex, received through well-established reciprocal cortico-cerebellar connections. Here, we test this hypothesis in a right-handed woman (EG) who lacks most of her left temporal lobe (presumably, from birth) and whose neocortical language network resides in her right hemisphere. Using precision functional MRI in EG and a cohort of 74 typically developing adults, we find that EG's cerebellar language network shows a strong left-hemispheric bias, mirroring the atypical lateralization of language in her cerebral cortex, while preserving canonical topography and response profiles of the language-dominant cerebellar regions. Critically, however, EG's right cerebellar hemisphere also responds to language and even contains a language-selective region despite the absence of language regions in the neocortical left hemisphere. These findings challenge the view that cerebellar specialization critically requires contralateral neocortical inputs, and point instead to some degree of intrinsic neocortex-independent cerebellar organization.

Viral population dynamics are shaped by production and loss. For viruses of microbes, high standing levels of viral abundances are interpreted as evidence of high rates of viral-induced cellular loss and viral production, followed by rapid extracellular viral decay. Here we reassess assumptions of rapid extracellular decay in 17 curated datasets, finding that biphasic decay either fits better or is statistically indistinguishable from exponential decay in approximately half the datasets. In addition to intrinsic heterogeneity in decay rates, biphasic decay at population scales can arise generically through aggregation mechanisms, where single virions decay and viral aggregates are protected. Integrating aggregation-induced biphasic decay into a virus-host model reveals that accounting for aggregation can recapitulate joint observations of high virion abundances and low infection prevalence, without assuming significant levels of uniformly inefficient infection. Together, our results suggest that durable extracellular virion persistence is environmentally relevant in shaping virus-microbe population dynamics.

Large language models (LLMs) can ease the work of screening titles and abstracts for systematic reviews, but obtaining reliable results requires researchers to make practical choices about which LLMs to use, how to combine their scores into a ranking, and how far down that ranking to read. We aimed to identify a general-purpose workflow that screens accurately, minimises human review effort, and generalises across environmental literature corpora. We ran an ensemble of five open-source LLMs across ten human-annotated systematic reviews from the field of ecology and environmental science spanning 19,777 studies. We then asked: (1) how well an ensemble of LLMs ranks relevant papers above irrelevant ones, and (2) where a human reviewer should stop working down that ranked list. A four-LLM ensemble chosen without any labels came close, on every review, to the best ranking achievable with that reviews annotations (mean Average Precision 0.64 versus 0.66). We tested different rules for when to stop human review, finding the SAFE stopping rule recovered[&ge;] 95% of relevant records on all ten reviews while requiring a human to screen 55% of the corpus on average. The paper offers a complete workflow that can be adopted for new, unlabelled reviews, using open-source LLMs small enough to run on a high-end consumer laptop, and we provide it as an open-source R package.

Active sensing systems are known to adapt the structure of sensory signals. Whether they can improve perception by controlling when sensory information is acquired remains unclear. We show that echolocating fruit bats exposed to rhythmic noise preferentially emit calls during recurring low-noise periods, a behaviour we term "dip echolocation". Dip echolocation occurred in laboratory and wild bats and represents an active-sensing analogue of dip listening in humans. A normative model showed that temporal positioning of calls emerges from a trade-off between sensory information and energetic cost, alongside concurrent adaptations of call structure. Pharmacological inactivation of the frontal auditory field disrupted precise temporal control, implicating a role for frontal cortical circuits in adaptive vocal timing. These findings identify adaptive vocal timing as an active-sensing strategy for overcoming acoustic interference.

During the lifetime of many animals, the microbiota fulfills multiple functions. After death of their hosts, these microbes contribute to cadaver decomposition, with implications for forensics, fossilization and soil nutrient and microbial community dynamics. Here, we draw attention to the possibility that host microbiota can also influence the evolution of pathogen lifestyles. We hypothesized that competition between microbiota and pathogens after host death can reduce benefits to pathogens of killing and decomposing their host. To test this hypothesis, we conducted infection experiments in which we injected the entomopathogenic bacteria Pseudomonas entomophila into Tenebrio molitor larvae. Our results show that bacterial proliferation after pathogen-induced host death occurs in larvae with strongly reduced microbiota, but not in larvae with intact gut microbiota. Strikingly, we found that gut microbiota can suppress the proliferation of an about 100 times larger pathogen population. In addition, we identified a microbiota member that might have mediated competitive suppression of pathogen proliferation after host death. Taken together, our results support our hypothesis that decomposing host microbiota can effectively compete with pathogens, thereby reducing the fitness of pathogens that kill and then exploit dead hosts. Based on a reanalysis of an existing theoretical model, we conclude that the host microbiota can facilitate the evolution of more benign pathogens that are less likely to kill their host for cadaver exploitation. Thus, our findings highlight the potentially important but so far unexplored possibility that pathogen-microbiota interactions in dead hosts can affect living hosts by influencing the evolution of pathogens lifestyles.