eLife

It is estimated that the evolution of segmented bilaterians occurred during the Ediacaran, whereas most of their unambiguous body fossils did not appear until Cambrian Stage 3. This fossil gap hampers our understanding of the early history of body segmentation, which is a crucial evolutionary innovation for bilaterians. Trace fossils from the late Ediacaran and basal Cambrian suggest this gap is likely to represent a taphonomic bias, implying that the progenitors of segmented bilaterians that existed within this temporal span were hardly preserved. Here, we report a variety of segmented bilaterians from the lowermost Cambrian of South China. These fossils are preserved as microbial pseudomorphs, rather than as ordinary phosphatization. These findings demonstrate that microbial pseudomorphs represent a major pathway for the preservation of segmented bilaterians during this period, as well as an effective mechanism for overcoming the taphonomic bias that affects micro-animals with delicate, non-biomineralized bodies. Moreover, the newly described animals, among the earliest segmented bilaterians, reveal a high diversity of segmented bilaterians during Ediacaran-Cambrian transition, shedding new light on the evolution of body segmentation.

We conducted a multi-ancestry genome-wide association study (GWAS) of developmental defects of enamel (DDE) in the primary dentition among 6,061 U.S. preschool-aged children (3--5 years). We investigated four DDE phenotypes (demarcated opacities, diffuse opacities, hypoplastic defects, and a combined DDE trait) leveraging main-effect models, joint gene-sex interaction testing (2df), and sex-stratified analyses. SNP-based heritability for the combined DDE trait was estimated at 20%, with concordance analyses robustly supporting a genetic etiology. We identified 39 unique genome-wide significant loci (P<5 x 10-8;), with five surpassing a study-wide Bonferroni-corrected statistical significance criterion (P<1.25 x 10-9), including Y RNA and ALDH1A1. The main-effect GWAS identified 20 loci, including HBS1L and MYB, genes regulating hematopoiesis with plausible roles in amelogenesis. Joint test and sex-stratified analyses revealed 19 additional loci, including ALDH1A1, TENM2, and DLGAP2, demonstrating sex-specific heterogeneity. Nineteen loci exhibited sex-specific differences after Bonferroni correction (P<2 x 10-3), including genes involved in retinoic acid signaling (ALDH1A1), odontogenesis (TENM2), and neurodevelopment (DLGAP2, CDH10). Pathway enrichment highlighted ectodermal and synapse organization networks, suggesting shared etiological mechanisms between DDE and systemic conditions like neurofibromatosis and autism spectrum disorder. Notably, no locus generalized in an external GWAS of permanent dentition DDE, underscoring fundamental biological differences in the genetic architectures governing primary versus permanent enamel formation. Crucially, a comprehensive cross-trait pleiotropy lookup against early childhood caries (ECC) revealed no shared genetic architecture, supporting the notion that the established clinical and epidemiological association between DDE and ECC is likely driven by structural defects increasing caries lesion susceptibility rather than genetic pleiotropy. By integrating gene-sex interaction testing, this study offers novel insights into the complex, sexually dimorphic genetic etiology of DDE and augments the biological evidence base that can support the development of precision pediatric dentistry.

Gasdermins are pore-forming effectors that mediate pyroptosis, an inflammatory form of programmed cell death characterized by membrane permeabilization and the release of intracellular contents. Phylogenetically, gasdermin members can be broadly divided into two major branches, the GSDME/PJVK branch and the GSDMA/B/C/D branch. Whereas the GSDME mediated pyroptosis was traced back to metazoans, the functional origins of GSDMA/B/C/D branch remain poorly understood. As a basal representative of the GSDMA-D lineage in cartilaginous fish, Callorhinchus milii GSDMA/B (CmiGSDMA/B) provides essential information for the ancestral state of this branch. Here, we functionally characterized CmiGSDMA/B and identified CmiCASP1 as its upstream protease. Mechanistically, Lipopolysaccharide (LPS) activates CmiCASP1 via its CARD domain, leading to cleavage of CmiGSDMA/B into two functionally distinct products, N241 and N288. N241 binds cell membrane to drive pyroptosis, whereas N288 suppresses N241-triggered cell death. Interestingly, N241 exhibits bactericidal activity against Gram-negative bacteria in vitro, suggesting that antimicrobial activity may have been an early feature of the GSDMA-D lineage. Collectively, these findings provide insight into a non-canonical, LPS-responsive, caspase-driven pyroptosis pathway in cartilaginous fish and reveal the dual-fragment antagonistic regulation within this branch.

Despite being rare among circulating natural killer (NK) cells and expressing 10-fold less CD16 than the predominant CD56dimCD16bright population, CD56dimCD16dim NK cells are expanded in HIV long-term elite controllers, yet their capacity to kill HIV-infected cells remained untested. Here, we show that these rare cells are the dominant effectors against HIV-infected T-cells, mediating approximately 4-fold higher direct cytotoxicity and 3-4-fold higher antibody-dependent cellular cytotoxicity (ADCC) than CD56dimCD16bright cells, and serially engaging multiple targets. This advantage is intrinsic, unexplained by cytotoxic granule content or inhibitory receptors recognizing MHC class I. Direct killing depends on NKG2D recognition of Vpr-induced ligands, with NKG2D elevated on CD56dimCD16dim cells; ADCC requires both NKG2D and ADAM17-mediated CD16 turnover for serial engagement. These findings explain the elite-controller reorganization, reveal that NK effector dominance is target-tuned rather than fixed (CD56dimCD16negative cells dominate against K562 cells), and identify high-NKG2D CD56dimCD16dim cells as the effector population HIV therapies should reproduce.

Importance: The transition from medical school to residency forms a national training network, yet its large-scale structure and implications for trainee outcomes remain poorly characterized. Objective: To evaluate the US residency match as a network and assess how institutional position relates to residency placement, educational debt, and specialty choice. Design: Cross-sectional analysis of publicly reported 2025 residency match outcomes. Setting: 107 US MD-granting medical schools and 301 residency institutions with available match data. Participants: 14,616 US MD students matching into residency in 2025 (convenience sample). Exposure: Institutional position within the residency match network, quantified using PageRank network centrality. The relative strength of each school's graduating class was defined as the median centrality of residency destinations across graduates (placement score). Main Outcomes and Measures: Residency placement outcomes, mean medical school debt at graduation, and specialty choice (primary care vs surgical specialties) in relation to institutional position within the residency match network. Network-derived measures were also compared with NIH funding, residency reputation, and student selectivity. Results: Among 14,616 US MD students matched across 107 medical schools and 301 residency institutions (approximately 73.5% of total US MD cohort), network-derived measures of institutional influence closely aligned with benchmarks of institutional standing such as NIH funding, residency reputation, and student selectivity (Spearman's Rho; = 0.72-0.86; all p < .001). Graduate outcomes varied systematically across institutions. Graduates of highly connected medical schools were more likely to match into highly connected residency programs (87.3% for top-quintile vs 41.0% for bottom-quintile schools). Schools with higher placement scores had graduates with lower educational debt, reduced entry into primary care, and increased entry into surgical or competitive specialties. Compared with bottom-decile schools, top-decile schools (stratified by placement score) had 37% lower mean graduate debt, 24% lower primary care entry, and 75% higher surgical specialty entry. Higher educational debt was not associated with entry into higher-compensated specialties. Conclusions and Relevance: The residency match network reflects a hierarchical structure of institutional standing. Graduates of higher- and lower-positioned medical schools experience systematically different residency placement outcomes. These findings provide a population-level, behavior-based perspective on institutional influence and its relationship to training pathways.

TULIP (TUbular LIPid binding) domain proteins (TDPs) are found in all living organisms including bacteria. They have various documented functions, some of which clearly related to their intra- or extracellular lipid transfer activities. Extracellular, BPI-related TDPs of insects (B-TDPs, also known as Takeout-related proteins), are often found in chemosensory organs, but little is known regarding their exact location or how they could contribute to olfaction or gustation. We have surveyed and updated the full set of Drosophila B-TDPs and found that roughly 50% are overexpressed in chemosensory organs. Focusing on three genes clustered on the third chromosome, we provide evidence that at least one of the encoded proteins is secreted in the lymph cavity housing the dendrites of olfactory neurons. Biochemical data give support for a putative function of B-TDPs as odorant transporters, but loss-of-function analyses also hint to a potential role as a barrier against plant-emitted terpenoids.

Virtual memory T cells are increasingly recognized as a functionally distinct lineage within the CD8 T cell pool, but when and how commitment to the lineage is enforced remain poorly understood. Here we demonstrate that TVM lineage choice is exceptionally sensitive to dosage and repression competence of the key T cell transcription factor Bcl11b. Three different genetic models of slightly reduced Bcl11b each biased CD8 cell development to TVM generation without deregulating effector differentiation. Timed conditional knockouts and adoptive transfers narrowed the developmental window and showed that Bcl11b levels determine diversion to virtual memory fate uniquely during intrathymic positive selection. Whereas total Bcl11b loss disrupts TCR signalling, a <2-fold dose reduction of Bcl11b enhanced selective responses to TCR stimulation. Chromatin accessibility profiling and single cell RNA-seq indicated that Bcl11b dose reduction redirects cells to the TVM fate, from the late cycling fraction of mature CD8SP thymocytes, by a mechanism independent of previously described cytokine-driven pathways.

Speech and music consistently differ in their acoustic rhythms, despite the cross-cultural diversity in their surface forms. Here, we investigate whether speech and music rhythms are rooted in distinct intrinsic timescales of the sensorimotor system, which are separately recruited to support individual communication and group synchronization, respectively. Corpus analysis revealed that the timescales dominating speech (4-8 Hz) and music rhythms (< 2 Hz) separately emerge in infant laughter, babbling and cries, and that both speech and song rhythms mature at about age three. The functional division between the two timescales is further probed through sensorimotor synchronization experiments, in which participants vocalize or tap to sound sequences presented at different rates. The rhythm produced by individuals is strongest between 4 and 8 Hz. In contrast, the produced rhythm is best synchronized among participants below 2 Hz. Collectively, these findings reveal two characteristic timescales in the human sensorimotor system, i.e., a faster (4-8 Hz) timescale reflecting resonance in individual production and a slower (<2 Hz) timescale that fosters interpersonal synchronization. The two timescales provide plausible biological basis for the rhythms of speech and music.

Cellular rotation is an understudied mechanism that regulates animal morphogenesis. In C. elegans, the dorsal-ventral axis is established when the two-cell-stage AB cell rotates within the eggshell as it divides, generating the diamond-shaped blastomere arrangement at the four-cell stage that enables distinct cell fate specification. Multiple mechanisms, including actomyosin-dependent oriented division, chiral cortical flow, and eggshell shape, have been proposed to regulate this arrangement, but whether these represent conflicting hypotheses or co-acting mechanisms remains unclear. Here, we show that CUL-3-actomyosin-dependent oriented division, eggshell geometry, and the Ras-MAPK signaling pathway regulate distinct steps of cellular rotation. AB cell rotation occurred in two distinct phases: Phase I during AB cytokinesis and Phase II during cytokinesis of the neighboring P1 cell. Quantitative analysis revealed that CUL-3-actomyosin-dependent oriented division is the only one of these three pathways that regulates the AB division axis before anaphase. Actomyosin-dependent oriented division and eggshell geometry were both required for Phase I rotation, whereas Phase II rotation was independent of eggshell geometry. We further identified the Ras-MAPK signaling pathway as a regulator of AB cell rotation that acts independently of eggshell geometry. Strikingly, the CUL-3-actomyosin-dependent pathway may have two distinct roles: first, specifying the AB division axis, and second, correcting the division axis in all cell types during cytokinesis. Together, these functions contribute significantly to cellular rotation and dorsal-ventral axis establishment.

Terminal Schwann cells (tSCs) are specialized glial cells persistently residing at the neuromuscular junction (NMJ), where they are widely postulated to participate in synaptic transmission and maintenance. However, elucidating their precise in vivo roles has been hindered by a lack of tSC-specific genetic models, as conventional tools simultaneously targeted axonal Schwann cells. Here, we identify Col20a1 as a highly specific marker for tSCs through single-cell transcriptomic analysis and establish a novel Col20a1-CreERT2 knock-in mouse model. Utilizing this model, we achieved highly specific systemic labeling and ablation of tSCs during the postnatal maturation window. Surprisingly, systemic tSC loss disrupted neither gross NMJ architecture nor overall motor behavior. Instead, electrophysiological and ultrastructural analyses revealed profound pre-synaptic defects, characterized by increased spontaneous miniature endplate potentials (mEPPs), accelerated synaptic depression during high-frequency stimulation, and significant physical depletion of pre-synaptic vesicles. Furthermore, long-term analysis revealed a robust glial repopulation that sustained prolonged neuromuscular integrity. Together, our findings establish Col20a1 as a definitive genetic handle for tSC research, delineating that while tSCs are dispensable for macroscopic synaptic structure, they serve a precise and critical role in regulating pre-synaptic vesicle homeostasis.

It is widely believed that starvation favours the processing of food-related cues, a notion here called the adaptive specificity hypothesis. Indeed, in Drosophila melanogaster starvation is required for appetitive odour-sugar but not for aversive odour-shock memory. Results from Gruber et al. (2013) and Meschi et al. (2024), however, suggest that starvation improves aversive short-term memory, too, challenging this hypothesis. We survey how starvation affects Drosophila associative olfactory short-term memory across 26 learning tasks. These tasks differ in the reinforcers and the amount of training, the life stage of the animals, in the predictive structure and associative timing of the task, in whether memory is expressed as an increase or decrease in odour preference, and in whether the learned behaviour is motivated by obtaining reward or avoiding/ escaping punishment. In adult flies, an improvement was observed for appetitive odour-sugar memories, whereas all tasks yielding aversive memory were unaffected. Strikingly, appetitive tasks that are not sugar-related, namely odour-shock extinction learning and punishment-relief associations, were either unaffected or even impaired, supporting the adaptive specificity hypothesis. In contrast, in 5-day-old larvae sugar-related appetitive associations were compromised, and the same was observed, to varying degrees, in larvae starved one day earlier and for aversive quinine associations, challenging the adaptive specificity hypothesis. Furthermore, we observed starvation-induced changes in locomotion and preference for a subset of the cues used in our study. Our results defy a simplistic interpretation in terms of the adaptive specificity hypothesis and call for case-by-case analyses of how starvation affects learning and behaviour.

During meiotic prophase I, the chromosome axis orchestrates programmed DNA double-strand break formation, repair and synapsis between homologous chromosomes. In mammals, the axis is assembled from the coiled-coil elements SYCP2 and SYCP3 that come together with the HORMA-domain proteins HORMAD1 and HORMAD2, but how these components associate into a coherent structural unit remains incompletely understood. Combining recombinant reconstitution, mass photometry, SEC-MALS, AlphaFold modelling and crosslinking mass spectrometry, we show that the HORMA domains of HORMAD1 and HORMAD2 form a selective pseudosymmetric heterodimer independently of either proteins own closure motif, with interface determinants conserved across vertebrates. We identify a previously unrecognised second closure motif (CM2) in SYCP2 that preferentially binds HORMAD1, distinct from the previously described HORMAD2-binding closure motif (CM1). Together, these results revise the current model of mammalian axis assembly and define a tripartite SYCP2-HORMAD1-HORMAD2 module as a fundamental structural unit of the mammalian meiotic chromosome axis.

The yellow fever mosquito, Aedes aegypti, is a vector of Zika, Dengue, Chikungunya and yellow fever, disease-causing viruses impacting millions of people annually across the globe. Female mosquitoes transmit pathogens through serial blood-feeding, while both male and female mosquitoes feed on plant resources. Contact chemosensation (taste) guides these two feeding modes in both positive ways, feeding readily on sugar in nectar or ATP in blood, and negative ways, demonstrating aversion to chemically diverse bitter compounds in blood or sugar meals. Here, we identify a receptor, AaegGr14, that is expressed in neurons in the labellum and cibarium of the mosquito. Activation of Gr14-expressing neurons causes reduced feeding, while Gr14 and Gr14-expressing GRNs are required for aversion to bitter compounds during nectar- but not blood-feeding. This work provides a molecular and cellular on-ramp to understand bitter taste in mosquitoes and establishes that there are feeding context-dependent differences in how taste mechanisms influence blood- and nectar-feeding. Understanding the molecular and cellular basis of bitter taste in mosquitoes during nectar- and blood-feeding will help inform vector control strategies and elucidate shared principles and unique aspects of insect taste systems.

Decision making often requires the integration of noisy bottom-up sensory evidence with top-down prior expectations learned from past experiences. Acetylcholine and noradrenaline have been proposed to shape these computations, yet it remains unclear whether they directly influence the weighting of sensory evidence and prior expectations during decision making or instead shape the learning process that gives rise to these expectations. To disentangle this, healthy participants (n = 62) completed a perceptual decision-making task under the influence of either the muscarinic acetylcholine receptor antagonist biperiden, the {beta}-adrenoceptor antagonist propranolol, or placebo, in a within-subject crossover design. The task required the integration of sensory evidence with learned expectations. The reliability of these two sources of information varied independently. We show that both drugs led to a faster updating of current beliefs in response to new evidence. Under propranolol, these effects were specific to reward outcomes, whereas under biperiden, faster updating in response to both reward and non-reward outcomes resulted in less stable beliefs. Notably, neither drug affected the degree to which choices were governed by the strength of the sensory evidence. Together, these findings suggest that acetylcholine and noradrenaline guide perceptual decision making by modulating the updating of top-down prior expectations in response to new bottom-up evidence during learning.

BackgroundOrgan weights are often divided by body weight to report "relative" organ size. Yet ratios usually stay size-dependent and become misleading. We built a simple decision path for size adjustment and wrapped it in a Shiny application so physiologists can get correct answers without coding. MethodsWe reused liver and body-weight data from a mouse nutrition study for confirmatory examples in two common cases: when diet groups shared a wide body-size range, and when diet produced much smaller animals with little overlap. We compared liver-to-body-weight ratios with size-adjusted regression when the body-size overlap allowed comparisons, and with causal Bayesian mediation when it did not. The full workflow was implemented in OrganScaleR, a guided R Shiny application. ResultsThe ratio-normalized organ weight is still associated with body weight, leading to misleading comparisons. Modeling liver weight against body weight gave more cautious, size-adjusted effects when groups shared a common size range. When diets shifted body size strongly and overlap was limited, causal mediation showed that most organ differences followed the change in body weight rather than an organ-specific action. Simulations confirmed that ratios can generate false positives and biased estimates under allometric scaling, while model-based approaches remained reliable. OrganScaleR implements this decision workflow in a guided Shiny application that returns interpretable effects. ConclusionsOrganScaleR selects scale, enforces common support, and routes the analysis to size-adjusted ANCOVA or causal Bayesian mediation depending on body-weight overlap. It reports adjusted effects in original units through a point-and-click workflow, removing the statistical barrier to abandoning ratio normalization. HighlightsO_LIBody-weight ratios remain size-dependent and distort organ-weight comparisons. C_LIO_LIANCOVA at a common reference body weight removes ratio bias when groups overlap. C_LIO_LICausal mediation separates organ-specific from body-weight-mediated diet effects. C_LIO_LISimulations confirm ratios inflate false-positive rates under allometric scaling. C_LIO_LIOrganScaleR guides size adjustment without coding via a point-and-click workflow. C_LI

The caudal fin is an anomaly among vertebrate locomotory appendages: its internal skeleton is as asymmetric as the human hand, but it lacks the Shh-secreting Zone of Polarizing Activity (ZPA) and the Gli3/HoxD/Hand2 programs that govern anterior-posterior patterning in other appendages. As the caudal fin was also the first appendage to evolve, deciphering its alternative patterning program may provide clues to the ancestral state. Pax9 is one of few conserved appendage patterning factors reported to also be active in the caudal fin, specifically in the anterior domain. We report that loss of pax9 function in zebrafish not only disrupts anterior-specific caudal fin anatomy, but also results in a spectacular fusion of the caudal and anal fins along the ventral midline. The dorsal fin is also expanded to a lesser degree, the paired fins not at all. The mutant caudal fin initially forms as an irregularly patterned structure lacking anterior molecular identity, with supernumerary elements spilling out beyond the normal anterior boundary. Unexpectedly, this phenotype is subsequently compounded by neighboring trunk somites erroneously deploying skeletal mesenchyme in the normally finless caudal peduncle region, completing the ectopic skeleton. scRNAseq analysis at caudal fin bud stage indicates that pax9 mutants gain skeletal mesenchyme at the expense of a specialized type of fibroblast involved in the formation of fin fold actinotrichia. Median fin skeletal mesenchyme and fin fold fibroblasts both arise from the sclerotome, a somite compartment that also robustly expresses pax9. We propose that, within the sclerotome, Pax9 pushes progenitors towards fin fold fibroblast fate, limiting how many cells will later be available to make median fin skeleton. Within the fin bud, it drives anterior identity, with the strongest impact on the ZPA-free caudal fin bud. These dual sites of action make Pax9 a uniquely powerful governor of median fin development.

Habituation--the decrement in response to a series of stimuli--is a widespread form of learning observed across many organisms, including the unicellular organism Stentor coeruleus. A lesser-known feature of Stentor habituation, shared with animals, is potentiation: faster habituation to a second stimulus series despite partial or complete recovery of responsiveness before that series begins. This suggests that although the first-order habituation memory can decay during the recovery period between the two series, a persistent second-order memory mediates faster relearning. We investigate the response profile of Stentor across a range of stimulation frequencies and recovery periods to identify the timescales at which these memory traces operate. We introduce a statistical framework to infer both population and single-cell learning parameters, allowing us to quantify prior qualitative findings and examine relationships among parameters across cells. Two key findings are that potentiation is frequency-sensitive, and that recovery and potentiation are decoupled, consistent with a serial and hierarchical cascade of leaky integrator units underlying these processes. This quantitative portrait provides a foundation for mechanistic modeling of intracellular memory in Stentor.

The intestinal mesentery has been recently classified as a 'new' organ and contains various cell types including adipocytes, preadipocytes, endothelial cells, and immune cells. In addition, neuronal cell bodies are found in the small intestinal mesentery and are situated either individually or clustered together with glial cells in small ganglion structures close to the gut wall. However, little is known about the origin or function of these extra-intestinal mesenteric neurons. The aim of this study was to better these characterize mesenteric neurons and to examine their connectivity with the ENS using calcium imaging in adult mouse ileum with the mesentery attached. Here we show that neurons in the mesentery express typical ENS neurochemical markers, respond to 5-HT, ATP and the nicotinic agonist DMPP, and receive nicotinic synaptic inputs. Furthermore, using labeling with the neuronal tracer DiI, some mesenteric neurons were found to project into the gut wall and can provide functional excitatory inputs to myenteric neurons. By contrast, we did not find evidence for mesenteric neurons providing inputs to other extrinsic neuronal targets, suggesting that they preferentially interact with the ENS. We also demonstrate that mesenteric neurons can be activated by intestinal distension and that the mesentery provides a source of inhibition to the myenteric plexus. Taken together, we show that the ENS not only interacts with vagal and spinal afferents, and sympathetic and parasympathetic nerves, but also neurons situated in the mesentery. Finally, our data suggest that these neurons may provide a form of negative feedback to the myenteric plexus such as in the event of intestinal distension. These findings have important implications for the regulation of intestinal motility in physiological and pathophysiological conditions.

Lactate dehydrogenase A (LDHA) is a key glycolytic enzyme that commonly exhibits altered expression in human diseases such as cancers and neurodegeneration, making it a valuable disease biomarker and putative therapeutic target. However, any treatment targeting LDHA will also disrupt normal metabolism, underscoring the need to investigate physiological consequences of inhibiting this enzyme. We previously established the fruit fly Drosophila melanogaster as a genetic model for studying LDH function in the context of growth, metabolism, and development. Here we expand upon those studies by investigating a serendipitous observation that Ldh mutant larvae exhibit diet-dependent lethality. Using a multiomic approach, we discovered this diet-dependent phenotype is independent of nutritional composition. Instead, Ldh mutant larvae are exercise intolerant and display reduced mobility, rendering mutant larvae sensitive to food consistency. Moreover, tissue-specific analysis reveals that LDH activity within muscle and peripheral glia are essential for larval viability raised on solid food. Intriguingly, these phenotypes mirror the pathophysiology of LDHA deficiency (Glycogen Storage Disease Type XI; GSD Type XI) in humans, where mild symptoms are exacerbated by physical exertion and environmental stress. Together, our findings further highlight the value of using Drosophila to explore the developmental and physiological consequences of Ldh inhibition.

Stratigraphic paleobiology is a newly established interdisciplinary approach, which has demonstrated that the fossil record is a joint expression of biotic and stratigraphic change, and all inferences from it must be grounded in a solid understanding of the stratigraphic context. Fossiliferous strata can be found in all depositional systems (e.g., marine, terrestrial, or lacustrine; siliciclastics or carbonates), each having a unique characteristic timescale and set of external controls, which govern the accumulation of sedimentary particles, including fossils. Consequently, the same biotic changes are preserved differently across depositional systems. While carbonate systems form a large portion of the fossil record, most studies in stratigraphic paleobiology have focused on siliciclastic systems and are not easily generalizable. As they are predominantly formed by living organisms, carbonates are both fossils and record, opening the opportunity to study the co-dependency of life and its environment. Here, we explore the stratigraphic paleobiology of carbonate systems by combining simulations of carbonate platform and ramp geometries with synthetic fossil records. We explore the preservation of extinction patterns and rates spatially and across geometries. By examining stratigraphic biases in isolation (unconformity and condensation, ecology, and abundance biases), we find characteristic differences between ramp and platform geometries due to their differential response to sea level change, spatial variability, and differences in ecological clines. Differences in the structure of the fossil record between platform geometries are traceable to the contribution and properties of the carbonate producing organisms (carbonate factories), showing that preservation of earth system data in carbonate systems will vary both latitudinally and temporally or as a result of major perturbations of the biogeosphere. Our results show that while general rules on the structure of the fossil record can be derived for entire depositional systems, accounting for the geological and ecological dynamics of a particular sedimentary basin can hugely refine interpretations of the fossil record. That is particularly true for biogenic and biologically-mediated sediments.