Lead author Dr. Pietro Pollo from UNSW Science explains that the selection of research topics is often influenced by factors that have little to do with scientific necessity or ecological importance. Instead, researchers are swayed by personal preferences and cultural attitudes, including the impact of popular media. Films, television shows, and even visits to zoos play a surprising role in shaping the scientific agenda. For instance, the widespread popularity of the animated film Finding Nemo may have inspired a generation of individuals to pursue careers in marine biology, specifically focusing on fish species that are visually appealing or culturally prominent. This cultural imprint on scientific inquiry means that the organisms we study are often those we find cute, exciting, or familiar, rather than those that are most critical to understanding the full scope of life on Earth.

The consequences of this bias are stark. Birds and mammals, which are the most visible and often the most charismatic groups of animals, dominate the research landscape. However, these vertebrate groups make up only a tiny fraction of overall biodiversity. In contrast, less popular animals such as insects, spiders, slugs, and worms receive far less attention. These invertebrates, which constitute the vast majority of animal species, are often overlooked in favor of their more well-known vertebrate counterparts. This disparity means that our understanding of the natural world is incomplete, with large gaps in our knowledge of the organisms that actually make up the bulk of life on the planet. The scientific community is, in effect, studying a small, biased sample of biodiversity while ignoring the rest.

To quantify this bias, the researchers analyzed more than one million ecology and evolution papers. The findings were revealing: vertebrates appeared in more than half of the papers involving animals, despite making up just 4.7% of described animal species. This statistic underscores the extent to which scientific attention is misaligned with the actual distribution of life on Earth. Furthermore, the study found that studies of vertebrates attract more citations and media attention than studies of invertebrates published in the same journals. This suggests that the bias is not only in the selection of research topics but also in the perception of their importance and impact. The scientific community tends to value and promote research on charismatic species, further entrenching the cycle of bias and neglect.

The researchers argue that this scientific blind spot manifests in unpredictable ways, making it difficult to anticipate the long-term consequences of ignoring certain groups of organisms. Basic research is inherently unpredictable, and it is impossible to know in advance which studies will lead to major breakthroughs. However, by focusing only on a narrow range of species, the scientific community risks missing out on potential discoveries. Dr. Pollo emphasizes that we do not know what we do not know, and that the next major discovery could be hiding in an organism that is currently ignored because it is not considered cute or exciting. This uncertainty underscores the importance of broadening the scope of scientific inquiry to include a more representative sample of life on Earth.

Historical examples illustrate the potential value of studying a wide range of organisms. Research into lizard saliva, for instance, helped lead to the development of drugs such as Ozempic, a medication used to treat diabetes and obesity. Similarly, fluorescent proteins discovered in jellyfish have transformed the study of individual cells, providing scientists with powerful tools for visualizing and understanding cellular processes. These examples highlight the importance of studying a broad range of organisms, as even the most unassuming species can hold the key to significant scientific and medical breakthroughs. By ignoring these less popular animals, the scientific community may be missing out on opportunities for innovation and discovery that could have far-reaching implications for human health and well-being.

The researchers call for a fundamental shift in how science is conducted, advocating for a broadening of training, outreach, and research opportunities to include a more representative sample of life on Earth. They argue that with millions of species and limited time and funding, it is essential to diversify research efforts as much as possible. This means not only studying a wider range of species but also ensuring that researchers are trained to appreciate and investigate the full diversity of life. By doing so, the scientific community can begin to address the blind spot that currently exists and develop a more comprehensive understanding of the natural world. This shift will require a change in mindset, moving away from a focus on charismatic megafauna and toward a more inclusive and representative approach to scientific inquiry.

The implications of this research extend beyond the scientific community, touching on broader issues of conservation, policy, and public engagement. If the scientific community is ignoring most living things, then the data used to inform conservation efforts and environmental policy may be incomplete or biased. This could lead to ineffective or misguided strategies for protecting biodiversity, as the most vulnerable or ecologically important species may be overlooked. Additionally, public engagement with science may be limited by the focus on charismatic species, as people may not be aware of the importance of less visible organisms. By broadening the scope of scientific inquiry, the community can help to raise awareness of the full diversity of life on Earth and foster a greater appreciation for the importance of all species, not just the most popular ones.

As the scientific community grapples with the challenges of a changing world, the need for a more inclusive and representative approach to research has never been more urgent. The bias toward charismatic megafauna is a reminder that science is not immune to human biases and cultural influences. By acknowledging and addressing this bias, the community can work toward a more complete and accurate understanding of the natural world. This will require a collective effort, involving researchers, educators, policymakers, and the public, to ensure that all species are given the attention they deserve. In doing so, the scientific community can not only fill the gaps in our knowledge but also unlock new opportunities for discovery and innovation, ultimately benefiting both the natural world and human society.

Subject of Research: Taxonomic bias in ecology and evolution research

Article Title: Researchers are ignoring most living things

Article References: Researchers are ignoring most living things. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: biodiversity, scientific bias, ecology, evolution, vertebrates, invertebrates, research methodology, UNSW, taxonomic diversity, conservation science, Researchers, ignoring

The review, authored by researchers synthesizing developmental, comparative, and human neuroimaging evidence, traces the origins of the nucleus tractus solitarius to embryonic structures shared across jawed vertebrates. Its neurons arise from the alar plate of the brainstem, and its sensory inputs come from placode-derived ganglia rather than neural crest, a developmental arrangement that has remained remarkably stable. This stability, the authors contend, explains why the fundamental architecture of the solitary tract system is recognizable in fish, amphibians, reptiles, birds, and mammals alike: a sensory tract converging on a medullary hub that connects peripheral signals with autonomic and behavioral outputs.

What changes across species is not what the nucleus does but how its circuits are emphasized. In fish, the system integrates chemical and mechanical signals from the aquatic environment, with no clear separation between upper and lower airway processing. Amphibians, facing the transition to air breathing, show expanded processing of oropharyngeal and airway signals. Reptiles, with fully established pulmonary respiration, display the neurological differentiation needed to distinguish airway compartments. Birds, equipped with a syrinx rather than a larynx, conserve the topographic organization of visceral inputs while adapting phonation control. Mammals, with their complex pharynx and larynx, exhibit the most elaborate coordination of swallowing, breathing, and vocalization. The review frames these differences as functional reweighting of conserved circuits rather than wholesale reorganization.

This comparative perspective sets the stage for the review’s most provocative claim: that the extensive supranuclear modulation observed in humans is not evidence of an improved brainstem but of layered control that became prominent under human-specific pressures. Speech, the authors argue, imposed extraordinary demands on a system originally designed to coordinate breathing with swallowing. The human larynx, descended relative to that of other primates, and the descended hyoid bone created anatomical conditions in which airway protection, phonation, and respiration had to be managed simultaneously with unprecedented precision. The nucleus tractus solitarius, as the primary convergence site for laryngeal and pharyngeal sensory inputs, became a critical node in this layered architecture.

The review rejects the framing of human supranuclear control as biological superiority, instead describing it as particularly prominent layered control shaped by human-specific constraints. Complex social communication, the authors note, required the brainstem to manage airway defense, respiration, and phonation in contexts far removed from the survival scenarios in which these circuits originally evolved. The result is a system in which ancient reflexive architecture remains intact but operates under extensive contextual modulation from higher brain regions.

Clinically, this perspective reframes several disorders. Dysphagia, the review argues, is not simply a failure of a single reflex arc but a breakdown of the layered coordination in which the nucleus participates. Cough hypersensitivity syndrome, similarly, reflects dysregulation of the inhibitory gating mechanisms that normally filter airway sensory inputs. Taste disturbances and feeding disorders, the authors suggest, involve disruption of the convergent pathways linking the nucleus with limbic and hypothalamic circuits. By treating these conditions as failures of network coordination rather than isolated reflex breakdowns, the review opens new avenues for therapeutic intervention.

The review’s final section addresses neuromodulation therapies, particularly vagus nerve stimulation. Rather than viewing stimulation as a simple activation of a peripheral nerve, the authors propose that it be understood as patterned modulation of the convergent sensory architecture in which the nucleus participates. This reframing, they argue, suggests that stimulation parameters might be optimized to target specific aspects of the layered control system, potentially offering more precise therapeutic outcomes for conditions ranging from epilepsy to depression.

The review’s synthesis carries implications beyond the clinic. By tracing the developmental origins, comparative organization, and human-specific modulation of the nucleus tractus solitarius, it demonstrates how a conserved sensory platform can be functionally reweighted across evolution while maintaining its fundamental architecture. The nucleus, the authors conclude, is not a primitive relay that humans have improved upon but a conserved sensory hub whose layered control reflects the extraordinary demands that speech, social communication, and complex ecological contexts have imposed on an ancient survival circuit.

Part of what makes the nucleus tractus solitarius such a compelling subject for cross-species comparison is that its developmental blueprint can be traced with unusual molecular precision. The sensory neurons that eventually populate the nucleus are specified by transcription factors including Nkx2.2 and Nkx2.9, while the adjacent branchial motor nuclei—structures the nucleus must ultimately cooperate with—depend on a separate genetic program centered on Phox2b. This means that two populations of neurons sitting side by side in the adult medulla actually follow strictly segregated lineages from the earliest stages of hindbrain patterning. The separation is not an accident of anatomy but a consequence of transcriptional regulation, and it provides the developmental substrate on which later functional coupling is built.

Modern mapping techniques have sharpened this picture considerably. Rather than arising from a vague dorsal region of the medulla, the nucleus in humans can be assigned to specific alar plate domains spanning rhombomeres seven through eleven, the caudal segments of the embryonic hindbrain. Gene expression data from human brain atlases suggest that neuronal identity within these segments is pre-patterned by conserved transcription factors, implying that the viscerotopic organization of the nucleus and the assembly of its circuits are genetically programmed rather than emergent byproducts of activity. In parallel, the peripheral inputs that feed the nucleus—the geniculate, petrosal, and nodose ganglia, which carry taste and visceral information—derive from epibranchial placodes rather than from the neural crest. This placodal origin distinguishes the visceral sensory lineage from many other cranial structures and reinforces the theme of developmental independence followed by functional integration.

The classical view of the adult nucleus as a neatly laminated viscerotopic map, with each organ’s afferents occupying a discrete subregion, has also been refined in recent years. Viral tracing studies of vagal afferents indicate that fibers from the gastrointestinal, cardiovascular, and respiratory systems are distributed far more broadly across the nucleus than the traditional textbook layout suggests. Individual neurons frequently receive convergent inputs from multiple organ systems, and the apparent topography reflects gradients of weighting rather than hard-wired compartments. This distributed convergence is precisely what allows the nucleus to act as an integrative node rather than a passive relay, and it helps explain how the same circuitry can support such diverse functions as baroreflex control, swallowing, and the coordination of breathing with vocalization.

The developmental separation of sensory and motor lineages, combined with their eventual functional coupling, offers a useful lens for thinking about complex behaviors. Swallowing, for example, is often described colloquially as a reflex, but it involves the precisely timed recruitment of dozens of muscles across the tongue, pharynx, and larynx, sequenced by central pattern generators that sit downstream of the nucleus. Airway protection during swallowing must be coordinated with respiration on a breath-by-breath basis, and in humans it must additionally be suspended during phonation. The review’s framing suggests that these behaviors are recombinations of neural elements with distinct developmental origins, assembled according to functional demand rather than inherited as monolithic reflex units. This perspective has practical consequences: a lesion that disrupts one component of the network may spare the reflex arc itself while degrading the coordination among components, producing clinical pictures that look like reflex failure but are actually failures of integration.

The network-level view also reframes how clinicians might think about diagnostic assessment and treatment targets. If dysphagia reflects a breakdown of layered coordination rather than a damaged reflex arc, then rehabilitation strategies that train the interaction between respiratory timing, laryngeal closure, and pharyngeal contraction may succeed where approaches targeting a single component do not. Similarly, cough hypersensitivity may respond better to interventions that restore inhibitory gating across the distributed sensory network than to those aimed at suppressing a single reflex pathway. The authors’ treatment of nausea and vomiting as network-level dysregulation points in the same direction, since emesis depends on coordination among visceral afferents, autonomic outputs, and behavioral responses that no single reflex arc could orchestrate alone.

The reframing of vagus nerve stimulation deserves particular attention because it connects evolutionary reasoning to a rapidly growing clinical field. If stimulation is understood as delivering patterned afferent input that shapes network plasticity within the nucleus, rather than as non-specific electrical activation of a peripheral nerve, then the design space for therapy expands considerably. Parameters such as pulse timing, waveform shape, and duty cycle could be tuned to engage specific classes of afferent fibers or to bias the nucleus toward particular integrative states. The evolutionary perspective adds a caution here: because the nucleus is a conserved hub whose components have been functionally reweighted across species, findings from animal models may not translate directly to humans, whose layered supranuclear control alters how afferent signals are interpreted. Therapies designed with this layered architecture in mind, the review suggests, are more likely to achieve the precision that current stimulation approaches have struggled to reach.

Ultimately, the synthesis underscores a broader principle in neuroscience: conservation of structure does not imply uniformity of function. The same developmental program, laid down in the hindbrain of every jawed vertebrate, has been repeatedly redeployed under different ecological and behavioral pressures, producing systems that share their wiring logic but differ profoundly in how that logic is weighted and controlled. The human nucleus tractus solitarius, operating under the demands of speech and complex social interaction, represents one particularly elaborate point on that continuum rather than a departure from it.

Subject of Research: Neuroscience

Article Title: The nucleus tractus solitarii across vertebrates: developmental origins, comparative organization, and supranuclear modulation in humans

Article References: Hong, Y.-S., & Park, Y.-S. (2026). The nucleus tractus solitarii across vertebrates: developmental origins, comparative organization, and supranuclear modulation in humans. Frontiers in Integrative Neuroscience, 20, Article 1768344. https://doi.org/10.3389/fnint.2026.1768344

Image Credits: AI Generated

DOI: 10.3389/fnint.2026.1768344

Keywords: brainstem, nucleus tractus solitarius, comparative neuroanatomy, speech, vagus nerve stimulation, evolution, nucleus, tractus, solitarii, across, vertebrates, developmental

The research, led by Pietro Pollo and Michael Kasumovic of the University of New South Wales, represents the most comprehensive assessment of taxonomic bias ever conducted in the field. Previous studies relied on small samples of journals and manual classification of papers, leaving open the question of whether the patterns documented in the early 2000s had persisted. To overcome these limitations, the team analyzed 1,383,803 papers from 612 journals, spanning literature published as far back as 1877, and tracked how the representation of different animal groups changed between 2001 and 2025.

Classifying papers by hand at this scale would have been impossible, so the researchers built a keyword-based algorithm trained on nearly 5,000 manually classified papers. The algorithm drew on the GBIF Backbone Taxonomy and a customized vocabulary of taxonomic terms to identify the animal focus of each paper from its title, abstract, and keywords. When tested against 1,815 papers the researchers had classified independently, the algorithm achieved at least 97.2 percent accuracy for every animal group, with an F1-score of 91.2 percent. The team also verified that the algorithm rarely produced impossible labels, such as identifying a paper in a mammalogy journal as being about something other than mammals.

The scale of the bias is striking. Of the 991,894 papers involving animals, 46.1 percent focused exclusively on invertebrates and 45.1 percent exclusively on vertebrates, figures that appear roughly balanced until one considers that invertebrates account for approximately 95 percent of animal species. When the researchers compared the observed proportion of papers on each group with what would be expected if research effort were distributed in proportion to species richness, insects emerged as the most underrepresented group relative to their diversity, while mammals and fish were the most overrepresented.

The study also documented how bias is embedded in the structure of the field itself. Nearly 40 percent of the 612 journals analyzed had explicit taxonomic restrictions, and a striking 42 percent of these specialized journals focused on arthropods. The researchers found that species-rich invertebrate groups such as insects and arachnids are often relegated to these specialized outlets, which likely reach narrower audiences than general ecology and evolution journals. This means the true extent of vertebrate favoritism may be even more pronounced from the perspective of an average researcher scanning the broader literature.

Perhaps most disappointingly, the overall pattern has shown no improvement since taxonomic bias was first formally discussed in 2002. The proportion of papers on vertebrates across the literature as a whole remained stable over the 25-year study period, and in some subfields it actually increased. In aquatic journals, for example, fish rose from 35.8 percent of papers in 2001 to 49.7 percent in 2025. In behaviour, conservation, and general ecology and evolution journals, mammals and birds remained particularly dominant. The only subfield where invertebrate research increased was zoology journals, likely because these outlets publish much of the work describing new species, the vast majority of which are invertebrates.

The researchers also examined whether journal prestige metrics were linked to taxonomic focus. Papers published between 2021 and 2025 in journals with higher impact factors and citation indicators were more likely to focus on vertebrates, although the relationship was not uniform across subfields. Interestingly, birds were equally likely to appear in high-impact and lower-impact journals, suggesting that the prestige advantage accrues to vertebrates as a broad category rather than to any single charismatic group.

The attention gap proved even more consequential than the publication gap. Compared with papers on invertebrates in the same journal, papers on vertebrates received on average 10.2 percent more citations, 43.1 percent more mentions in online documents such as news outlets and social media, 24.2 percent more readers on the reference manager Mendeley, and 45.1 percent higher Altmetric scores, a weighted measure of overall online attention. These findings align with previous research showing that vertebrates attract more attention on platforms like Instagram and Wikipedia, and even on government-curated imagery such as postage stamps. Within the attention metrics, birds often attracted the greatest online buzz but received the fewest citations, revealing that public appeal and academic influence do not always coincide.

The authors caution that their within-journal attention analyses are correlational and cannot fully rule out confounding factors such as paper topic. Still, they argue that the patterns likely reflect deeper societal biases, since surveys consistently show that people value vertebrates more than invertebrates, a perception that editors, reviewers, and funding committees may unconsciously apply when judging research appeal. The consequences extend beyond academic vanity: taxonomic bias can stifle medical and engineering innovation by limiting biomimetic inspiration from understudied organisms, and it undermines the theoretical generality that ecology and evolution depend upon.

To break the cycle, the researchers propose concrete interventions within academia. They urge journals and funding bodies to systematically collect and publicly report the taxa studied in submitted manuscripts and funded projects, to incorporate taxonomic diversity into guidelines for awards, hiring, and publication decisions, and to establish targeted financial and publishing incentives for research on neglected organisms. They also emphasize the need to revive descriptive disciplines such as taxonomy and natural history, since hypotheses cannot be tested about organisms that have never been described. While such measures may seem ambitious, the authors note that similar skepticism once greeted diversity initiatives that are now widely accepted, and they hope their findings will prompt institutions to extend their commitments to equity to the tree of life itself.

Subject of Research: Taxonomic bias in ecology and evolution research literature

Article Title: Taxonomic Bias Persists in Ecology and Evolution Research Despite Decades of Concern

Article References: Pollo, P., & Kasumovic, M. M. (2026). Taxonomic Bias Persists in Ecology and Evolution Research Despite Decades of Concern. Ecology and Evolution, 16(10), Article e74450. https://doi.org/10.1002/ece3.74450

Image Credits: AI Generated

DOI: 10.1002/ece3.74450

Keywords: taxonomic bias, ecology, evolutionary biology, vertebrates, invertebrates, journal impact factor, Altmetric, biodiversity, conservation, entomology, scientific publishing, citation bias

The evidence assembled by the team ranges from the charming to the downright bizarre. Consider the Hoffmann’s two-toed sloth, whose shaggy coat hosts a miniature ecosystem. Sloth moths live out their lives in the animal’s fur, and their activities help cultivate algae that grow in the sloth’s hair — algae the sloth then eats, supplementing its otherwise meadow-sparse diet of leaves. In this sense, the sloth is not merely tolerating its insect tenants; it is actively farming them, or at least farming the garden they fertilize. Remove the moths, and the sloth loses both a nutrient source and a living camouflage that helps it vanish into the canopy.

Other examples reveal insects serving as tools, infrastructure, and even medicine. Chimpanzees have been observed applying insects to open wounds, a behavior that appears to help sterilize injuries and may represent a form of self-medication. Herons, meanwhile, have turned insects into fishing equipment, using them as bait to lure fish within striking distance. Birds and reptiles lay their eggs inside termite mounds, exploiting the structures’ remarkably stable internal temperatures as natural incubators. In arid environments, some desert frogs take refuge inside ant nests, where the humidity offers a buffer against desiccation in landscapes where water is the scarcest resource of all.

“Insects are sometimes called the ‘little things that run the world’ because they are so important to life on Earth,” said Grames, the paper’s co-lead author. “We often hear about their importance as pollinators, or decomposers, or food for insectivores like birds and bats, but we forget about all the other things they do for us and for other species.” That observation captures the review’s core ambition: to move beyond the well-worn categories of pollination and predation and catalog the full breadth of insect-vertebrate relationships, many of which fall through the cracks of conventional ecological research.

The project was a genuinely international undertaking, with authors drawn from eight countries. Alongside Grames, the review was co-led by Rob Cooke, an ecological modeler at the UK Centre for Ecology and Hydrology, and Chris Elphick, professor of ecology and evolutionary biology at the University of Connecticut. Additional Binghamton contributors included Lindsey Swierk, assistant professor of biological sciences, and biological sciences alumni Julianna Yager and Suyeon Jang. In a fitting touch, Jang — an undergraduate with a painting minor — created the paper’s main illustration as an independent study project, translating the review’s scientific breadth into a single visual statement.

The effort traces its origins to 2022, when researchers established the Status of Insects: An International Research Coordination Network, an initiative funded by the National Science Foundation. The network emerged directly from Grames’ doctoral work in Elphick’s laboratory, and it was designed to confront a persistent problem in entomology and ecology more broadly: the literature on insect-vertebrate interactions is scattered across hundreds of individual studies, each examining a narrow slice of the picture. By consolidating that dispersed evidence into a single synthesis, the review offers the most comprehensive account yet of how deeply vertebrate life is woven into the fabric of insect diversity.

The scale of that dependence is difficult to overstate. There are an estimated 14 to 30 million species of insects on Earth, and they underpin the health and function of ecosystems on nearly every continent. They feed species ranging from hummingbirds, whose metabolisms demand near-constant refueling, to grizzly bears, which gorge on moths and other insects during critical seasons. Insects also enable other food sources indirectly through pollination, and they produce substances — honeydew, honey, and wax among them — that are themselves consumed by other species. For many vertebrates, insect abundance is not a background condition but a calendar: a variety of species time their breeding seasons to coincide with seasonal pulses of insect availability, synchronizing reproduction with the brief windows when their young can be fed.

The review also documents subtler forms of dependence that border on engineering. Birds incorporate spider and insect silk into their nests, taking advantage of materials with tensile properties that few natural substances can match. Some birds go further, deliberately situating their nests near stinging insects such as wasps, recruiting the colony’s venomous defenses as a security system against predators. More than 200 bird species use crushed ants for grooming — a behavior known as anting, in which the birds rub ants over their plumage, likely benefiting from the insects’ chemical secretions. And the relationship between insects and nesting vertebrates stretches deep into the past: insects once lived inside dinosaur nests, cleaning them out, and according to Grames, they still perform that sanitation service today in the nests of some owls and kingfishers.

Yet for all this richness, the scientific literature has a conspicuous blind spot. Few studies consider how insect population declines affect vertebrate species beyond the most obvious channel — a shrinking food supply. That narrow framing, the authors argue, dramatically understates the risk. If insects disappear, vertebrates lose not only calories but nesting materials, incubators, medicines, sanitation services, climate refuges, and the ecological timing cues that structure their reproductive cycles. Some insect populations have experienced alarming declines in recent decades, and those losses will ultimately propagate through the vertebrate communities that depend on them in ways that current research has barely begun to measure.

The numbers behind that warning are stark. “We’re losing insects at a rate of about 1-2% per year,” Grames said. “When you scale that up across a few decades, we’re talking about a major change to ecosystems. Insect conservation should be a top priority for anyone worried about the future of biodiversity.” A decline of even one to two percent annually, compounded over half a century, translates into a transformation of insect communities on a scale that has no precedent in recent ecological memory. Elphick, an ornithologist by training, framed the implication as a call for scientific bridge-building: he hopes the review will foster increased collaboration between scientists who study vertebrates and those who study insects. “If you want to have vertebrates, then you’ve got to be thinking about insect conservation, and we don’t do that nearly enough,” he said. In an era when conservation planning is often organized around charismatic vertebrates and their habitats, the review’s synthesis delivers a pointed reminder that the fates of sloths, songbirds, chimpanzees, and frogs are entangled with creatures small enough to escape notice — and that protecting the little things that run the world may be the surest way to protect everything that runs on them.

Subject of Research: The diverse roles of insect biodiversity in supporting vertebrate species

Article Title: Insects are essential to vertebrate life — as food, shelter and medicine

Article References: Insects are essential to vertebrate life — as food, shelter and medicine. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: insects, vertebrates, biodiversity, conservation, sloths, entomology, ecology, insect decline, termite mounds, chimpanzees, Nature Reviews Biodiversity, ecosystems

The research team, led by investigators at Stanford University including Chew Chai, Jesse Gibson, Pengyang Li, Brennan D. McDonald, Anusri Pampari, Aman Patel, Anshul Kundaje, and Bo Wang, set out to address a fundamental question in evolutionary biology: what mechanisms define and maintain families of related cell types across deep evolutionary time? Cell types can be organized into related families based on their functional and molecular properties, yet the regulatory underpinnings that sustain these families across hundreds of millions of years of divergence have remained largely unknown. By integrating single-nucleus multi-omic sequencing data from three species of flatworms and comparing it with vertebrate data, the researchers were able to identify hundreds of sequence motifs that dictate chromatin accessibility and partition into distinct, conserved sets referred to as vocabularies.

The concept of motif vocabularies represents a significant conceptual advance in the field. Each vocabulary is associated with a specific cell type family, meaning that the short DNA sequences recognized by transcription factors are not randomly distributed across the genome but instead cluster into coherent sets that define broad categories of cellular identity. When the researchers examined the combinatorial relationships among these motifs, they found that the particular combinations preferred by individual cell types are largely species-specific. This means that while the building blocks, the individual motifs themselves, remain stable across vast evolutionary distances, the ways in which those blocks are assembled into functional regulatory programmes evolve rapidly and independently in each lineage.

To dissect this layered organization, the team employed ChromBPNet, a deep-learning architecture designed to model chromatin accessibility at base resolution while factoring out technical biases introduced by the Tn5 transposase used in ATAC-seq library preparation. Models trained on chromatin accessibility data from one species accurately predicted family-level chromatin accessibility in distantly related species, demonstrating that the vocabulary-level information encoded in DNA sequences is conserved in a functionally meaningful way. However, interpretability analyses of the model predictions revealed a striking pattern: the deep-learning models frequently relied on different motifs from the shared vocabularies to arrive at convergent predictions. In other words, two species might achieve the same regulatory outcome for a given cell type family, but they do so by drawing on different members of the same motif vocabulary rather than by using identical regulatory elements.

The picture changes dramatically when the resolution of analysis shifts from the cell type family level to the individual cell type level. Models trained on chromatin accessibility data from a specific cell type within one species lost their predictive power when applied to the corresponding cell type in a distantly related species. This loss of cross-species transferability indicates that the regulatory syntax governing cell type-level identity, the precise arrangements and combinations of motifs that specify an individual cell type, evolves much more rapidly than the vocabulary-level constraints that define broader cell type families. The researchers refer to this hierarchical organization as a collective maintenance model, in which the identity of a cell type family is preserved not by any single conserved regulatory element but by the collective stability of a large pool of conserved regulatory factors.

This collective maintenance framework draws a compelling parallel to the concept of developmental homology in evolutionary biology. In homology, a character identity persists across species through conservation at the network level, even as the individual components of the network undergo extensive rewiring. The flatworm and vertebrate data suggest that cell type family identity operates under a similar logic: the vocabulary of sequence motifs defining a family is evolutionarily stable, yet the recombination of these motifs generates cell type-specific regulatory programmes that can differ substantially between species. This decoupling of family-level conservation from cell type-level innovation provides a mechanistic explanation for how new cell types can arise during evolution without disrupting the fundamental identities of existing cell type families.

The technical rigor underlying these conclusions is substantial. The researchers generated single-nucleus multi-omic sequencing data, capturing both gene expression and chromatin accessibility from the same individual nuclei, across three flatworm species: Schmidtea mediterranea, Schistosoma mansoni, and Macrostomum lignano. These species span a considerable range of evolutionary divergence within the flatworm phylum, providing a robust framework for comparative analysis. The team also extended their analysis to vertebrate systems by leveraging existing single-cell multi-omic data from mouse and zebrafish, two species separated by approximately 450 million years of evolution. The cross-species comparison between flatworms and vertebrates is particularly informative because these lineages diverged over 550 million years ago, representing one of the deepest evolutionary comparisons feasible with single-cell genomics.

Among the findings that emerge from this analysis is the observation that chromatin accessibility is conserved within cell type families even when the individual regulatory elements driving that accessibility are not. This means that the overall pattern of which parts of the genome are open and accessible in a given cell type family remains similar across species, but the specific DNA sequences responsible for opening those regions differ. The deep-learning models captured this distinction with remarkable fidelity, as they were able to predict family-level accessibility patterns across species using different combinations of motifs from the same conserved vocabulary. When the researchers examined neural cell types specifically, they documented extensive turnover in combinatorial motif usage, with individual neural cell types in different species employing different sets of motif pairs from the shared neural vocabulary to achieve their specific regulatory identities.

The implications of this work extend beyond basic evolutionary biology into the realm of biomedical research. Understanding that the vocabulary-level organization of regulatory motifs is conserved across species suggests that insights gained from model organisms about cell type family regulation may be more broadly transferable than previously appreciated, provided the analysis is conducted at the appropriate level of biological organization. Conversely, the rapid evolution of cell type-specific regulatory syntax means that extrapolating detailed regulatory mechanisms from one species to another requires caution, particularly for cell types that have undergone significant diversification. The collective maintenance model also raises intriguing questions about the evolutionary dynamics that maintain vocabulary stability while permitting combinatorial flexibility, and whether disruptions to vocabulary-level conservation might underlie certain developmental disorders or diseases.

As the field of single-cell genomics continues to expand the catalog of cell types across the tree of life, the framework developed in this study provides a conceptual scaffold for interpreting cross-species comparisons at multiple levels of resolution. The finding that conserved motif vocabularies constrain genome access while their flexible recombination drives cell type innovation bridges a persistent gap between the stability of cellular identities and the remarkable diversity of cell types observed across the animal kingdom. The research team has made all data and computational tools publicly available, including the single-cell multi-ome datasets deposited in the Sequence Read Archive, the ChromBPNet models shared through figshare, and the complete analysis code archived on GitHub and Zenodo, ensuring that the broader scientific community can build upon these findings to further unravel the regulatory architecture of cell type evolution.

Subject of Research: Evolutionary conservation of regulatory motif vocabularies governing chromatin accessibility and cell type family identity across flatworms and vertebrates

Article Title: Flexible use of conserved motifs constrains genome access in cell type evolution

Article References: Chai, C., Gibson, J., Li, P., McDonald, B. D., Pampari, A., Patel, A., Kundaje, A., & Wang, B. (2026). Flexible use of conserved motifs constrains genome access in cell type evolution. Nature Ecology & Evolution, 10(10), 1941-1958. https://doi.org/10.1038/s41559-026-03164-5

Image Credits: AI Generated

DOI: 10.1038/s41559-026-03164-5

Keywords: cell type evolution, chromatin accessibility, deep learning, single-cell multi-omics, motif vocabularies, regulatory syntax, flatworms, vertebrates, developmental homology, gene regulation, Nature Ecology & Evolution, transcription factors