The metabolomic physics of complex diseases.

Human diseases involve metabolic alterations. Metabolomic profiles have served as a vital biomarker for the early identification of high-risk individuals and disease prevention. However, current approaches can only characterize individual key metabolites, without taking into account the reality that complex diseases are multifactorial, dynamic, heterogeneous, and interdependent. Here, we leverage a statistical physics model to combine all metabolites into bidirectional, signed, and weighted interaction networks and trace how the flow of information from one metabolite to the next causes changes in health state. Viewing a disease outcome as the consequence of complex interactions among its interconnected components (metabolites), we integrate concepts from ecosystem theory and evolutionary game theory to model how the health state-dependent alteration of a metabolite is shaped by its intrinsic properties and through extrinsic influences from its conspecifics. We code intrinsic contributions as nodes and extrinsic contributions as edges into quantitative networks and implement GLMY homology theory to analyze and interpret the topological change of health state from symbiosis to dysbiosis and vice versa. The application of this model to real data allows us to identify several hub metabolites and their interaction webs, which play a part in the formation of inflammatory bowel diseases. The findings by our model could provide important information on drug design to treat these diseases and beyond.

G × E × M analysis to define allometric rules between leaves and stems in wheat.

Allometric rules provide insights into the structure-function relationships across species and scales and are commonly used in ecology. The fields of agronomy, plant phenotyping and modeling also need simplifications such as allometric rules to reconcile data at different temporal and spatial levels (organs/canopy). This paper explores the variations in relationships for wheat regarding (i) the distribution of crop green area between leaves and stems, and (ii) the allocation of above-ground biomass between leaves and stems during the vegetative period, using a large dataset covering different years, countries, genotypes and management practices. Our results show that the relationship between leaf and stem area was linear, genotype-specific, and sensitive to radiation. The relationship between leaf and stem biomass depended on genotype and nitrogen fertilization. The mass per area, associating area and biomass for both leaf and stem, varied strongly by developmental stage and was significantly affected by environment and genotype. These allometric rules were evaluated with satisfactory performance, and their potential use is discussed with regard to current phenotyping techniques and plant/crop models. Our results enable the definition of models and minimum datasets required for characterizing diversity panels and making predictions in various G × E × M contexts.

Sexually divergent selection, allometric constraints, and the evolution of sexual dimorphism in cichlids from Lake Tanganyika.

The evolution of sexual dimorphism is widely acknowledged as manifestation of sex-specific genetic architecture. Although empirical studies suggested that sexual dimorphism evolves as a joint consequence of constraints arising from the genetic architecture and sexually divergent selection, it remains unclear whether and how these established microevolutionary processes scale up to the macroevolutionary patterns of sexual dimorphism among taxa. Here, we studied how sexual selection and parental care drive sexual dimorphism in cichlid fishes from Lake Tanganyika. We found that male-male competition, female choice, and maternal mouthbrooding are associated with sexual dimorphism in body length, body color, and head length, respectively, despite strong allometric relationships between body length and head length. Within-species (static) allometry of head length on body length evolved as sex-specific responses to mouthbrooding where females evolved higher intercepts while males evolved steeper slopes. Thus, selection to increase mouth size in mouthbrooders may have broken down and reorganized the pattern of allometric constraints that are inherently strong and concordant between sexes. Furthermore, sex-specific responses to mouthbrooding left a remarkably clear signature on the macroevolutionary pattern, resulting in a decoupling of co-evolution in parameters of static allometries observed exclusively within maternal mouthbrooders. Our study provides multiple lines of evidence that are consistent with the idea that macroevolutionary patterns of sexual dimorphism in Lake Tanganyika cichlids result from sexually divergent selection. Our approach illustrates that an examination of within-population phenotypic variance in the phylogenetic comparative framework may facilitate nuanced understandings of how macroevolutionary patterns are generated by underlying microevolutionary processes.

Growth, filtration and respiration characteristics of small single-osculum demosponge Halichondria panicea explants.

Filter-feeding demosponges are modular organisms that consist of modules each with one water-exit osculum. Once a mature module has been formed, the weight-specific filtration and respiration rates do not change. Sponge modules only grow to a certain size and for a sponge to increase in size, new modules must be formed. However, the growth characteristics of a small single-osculum module sponge are fundamentally different from those of multi-modular sponges, and a theoretically derived volume-specific filtration rate scales as F/V=V-1/3, indicating a decrease with increasing total module volume (V, cm3). Here, we studied filtration rate (F, l h-1), respiration rate (R, ml O2 h-1), volume-specific (F/V) and weight-specific (F/W) filtration rates, and the ratios F/R and F/W along with growth rates of small single-osculum demosponge Halichondria panicea explants of various sizes exposed to various concentrations of algal cells. The following relationships were found: F/V=7.08V-0.24, F=a1W1.05, and R=a2W0.68 where W is the dry weight (mg). The F/R and F/W ratios were constant and essentially independent of W, and other data indicate exponential growth. It is concluded that the experimental data support the theoretical F/V∝V-1/3.

Plasticity, symbionts and niche construction interact in shaping dung beetle development and evolution.

Developmental plasticity is an important product of evolutionary processes, allowing organisms to maintain high fitness in the face of environmental perturbations. Once evolved, plasticity also has the potential to influence subsequent evolutionary outcomes, for example, by shaping phenotypic variation visible to selection and facilitating the emergence of novel trait variants. Furthermore, organisms may not just respond to environmental conditions through plasticity but may also actively modify the abiotic and (sym)biotic environments to which they themselves respond, causing plasticity to interact in complex ways with niche construction. Here, we explore developmental mechanisms and evolutionary consequences of plasticity in horned dung beetles. First, we discuss how post-invasion evolution of plasticity in an introduced Onthophagus species facilitated rapid range expansion and concurrent local adaptation of life history and morphology to novel climatic conditions. Second, we discuss how, in addition to plastically responding to variation in nutritional conditions, dung beetles engage in behaviors that modify the environment that they themselves respond to during later development. We document that these environment-modifying behaviors mask heritable variation for life history traits within populations, thereby shielding genetic variants from selection. Such cryptic genetic variation may be released and become selectable when these behaviors are compromised. Together, this work documents the complex interactions between plasticity, symbionts and niche construction, and highlights the usefulness of an integrative Eco-Evo-Devo framework to study the varied mechanisms and consequences of plasticity in development and evolution.

Contrasting biomass allocations explain adaptations to cold and drought in the world's highest-growing angiosperms.

BACKGROUND AND AIMS: Understanding biomass allocation among plant organs is crucial for comprehending plant growth optimization, survival and responses to the drivers of global change. Yet, the mechanisms governing mass allocation in vascular plants from extreme elevations exposed to cold and drought stresses remain poorly understood. METHODOLOGY: We analysed organ mass weights and fractions in 258 Himalayan herbaceous species across diverse habitats (wetland, steppe, alpine), growth forms (annual, perennial taprooted, rhizomatous and cushiony) and climatic gradients (3500-6150 m elevation) to explore whether biomass distribution adhered to fixed allometric or optimal partitioning rules, and how variations in size, phylogeny and ecological preferences influence their strategies for resource allocation. KEY FINDINGS: Following optimal partitioning theory, Himalayan plants distribute more biomass to key organs vital for acquiring and preserving limited resources necessary for their growth and survival. Allocation strategies are mainly influenced by plant growth forms and habitat conditions, notably temperature, water availability and evaporative demands. Alpine plants invest primarily in below-ground stem bases for storage and regeneration, reducing above-ground stems while increasing leaf mass fraction to maximize carbon assimilation in their short growing season. Conversely, arid steppe plants prioritize deep roots over leaves to secure water and minimize transpiration. Wetland plants allocate resources to above-ground stems and below-ground rhizomes, enabling them to resist competition and grazing in fertile environments. CONCLUSIONS: Himalayan plants from extreme elevations optimize their allocation strategies to acquire scarce resources under specific conditions, efficiently investing carbon from supportive to acquisitive and protective functions with increasing cold and drought. Intraspecific variation and shared ancestry have not significantly altered biomass allocation strategies of Himalayan plants. Despite diverse evolutionary histories, plants from similar habitats have developed comparable phenotypic structures to adapt to their specific environments. This study offers new insights into plant adaptations in diverse Himalayan environments and underscores the importance of efficient resource allocation for survival and growth in challenging conditions.

From a local descriptive to a generic predictive model of cereal aphid regulation by predators.

The temporal dynamics of insect populations in agroecosystems are influenced by numerous biotic and abiotic interactions, including trophic interactions in complex food webs. Predicting the regulation of herbivorous insect pests by arthropod predators and parasitoids would allow for rendering crop production less dependent on chemical pesticides. Curtsdotter et al. (2019) developed a food-web model simulating the influences of naturally occurring arthropod predators on aphid population dynamics in cereal crop fields. The use of an allometric hypothesis based on the relative body masses of the prey and various predator guilds reduced the number of estimated parameters to just five, albeit field-specific. Here, we extend this model and test its applicability and predictive capacity. We first parameterized the original model with a dataset with the dynamic arthropod community compositions in 54 fields in six regions in France. We then integrated three additional biological functions to the model: parasitism, aphid carrying capacity and suboptimal high temperatures that reduce aphid growth rates. We developed a multi-field calibration approach to estimate a single set of generic allometric parameters for a given group of fields, which would increase model generality needed for predictions. The original and revised models, when using field-specific parameterization, achieved quantitatively good fits to observed aphid population dynamics for 59% and 53% of the fields, respectively, with pseudo-R2 up to 0.99. But the multi-field calibration showed that increased model generality came at the cost of reduced model reliability (goodness-of-fit). Our study highlights the need to further improve our understanding of how body size and other traits affect trophic interactions in food webs. It also points up the need to acquire high-resolution data to use this type of modelling approach. We propose that a hypothesis-driven strategy of model improvement based on the integration of additional biological functions and additional functional traits beyond body size (e.g., predator space search or prey defences) into the food-web matrix can improve model reliability.

A Mathematical Model of Stroma-Supported Allometric Tumor Growth.

Mounting empirical research suggests that the stroma, or interface between healthy and cancerous tissue, is a critical determinate of cancer invasion. At the same time, a cancer cell's location and potential to proliferate can influence its sensitivity to cancer treatments. In this paper, we use ordinary differential equations to develop spatially structured models for solid tumors wherein the growth of tumor components is coordinated. The model tumors feature two components, a proliferating peripheral growth region, which potentially includes a mix of cancerous and noncancerous stroma cells, and a solid tumor core. Mathematical and numerical analysis are used to investigate how coordinated expansion of the tumor growth region and core can influence overall growth dynamics in a variety of tumor types. Model assumptions, which are motivated by empirical and in silico solid tumor research, are evaluated through comparison to tumor volume data and existing models of tumor growth.

Holy grail of tissue regeneration: Size.

Cells and tissue within injured organs undergo a complicated healing process that still remains poorly understood. Interestingly, smaller organisms respond to injury with tissue regeneration and restoration of function, while humans and other large organisms respond to injury by forming dysfunctional, fibrotic scar tissue. Over the past few decades, allometric scaling principles have been well established to show that larger organisms experience exponentially higher tissue forces during movement and locomotion and throughout the organism's lifespan. How these evolutionary adaptations may affect tissue injury has not been thoroughly investigated in humans. We discuss how these adapations may affect healing and demonstrate that blocking the most evolutionary conserved biologic force sensor enables large organisms to heal after injury with true tissue regeneration. Future strategies to disrupt tissue force sensors may unlock the key to regenerating after injury in a wide range of organ systems.

A systematic review of allometric scaling exponents for IgG mAbs.

Increasing complexity of mAbs in development creates challenges in predicting human pharmacokinetic (PK) parameters from preclinical data. The aim of this analysis was to identify optimal allometric scaling exponents.Data were extracted from literature to create a central database (currently the largest available published database) of two-compartment model parameters for mAbs (n = 59) in cynomolgus monkey (CM) and human.Global allometric exponents were calculated and drug-dependent factors were investigated as potential variables in determining the optimal scaling factor.The global exponents for scaling CM mAb PK data were 0.74 (CL), 0.80 (CL with Fc-modified mAbs excluded), 0.44 (CL with Fc-modified mAbs only), 0.71 (Q), 1.12 (V1), and 0.99 (V2). These values are in line with previously published literature values.

In vitro and in vivo preclinical pharmacokinetic characterization of aficamten, a small molecule cardiac myosin inhibitor.

Aficamten, a small molecule selective inhibitor of cardiac myosin, was characterised in preclinical in vitro and in vivo studies.Protein binding in human plasma was 10.4% unbound and ranged from 1.6% to 24.9% unbound across species. Blood-to-plasma ratios ranged from 0.69 to 1.14 across species. Aficamten hepatic clearance in human was predicted to be low from observed high metabolic stability in vitro in human liver microsomes. Aficamten demonstrated high permeability in Caco-2 cell monolayers.Aficamten in vivo clearance was low across species at 8.8, 2.1, 3.3, and 11 mL/min/kg in mouse, rat, dog, and monkey, respectively. The volume of distribution was low-to-high ranging from 0.53 in rat to 11 L/kg in dog. Oral bioavailability ranged from 41% in monkey to 98% in mouse.Aficamten was metabolised in vitro to eight metabolites with hydroxylated metabolites M1a and M1b predominating. CYP phenotyping indicated multiple CYPs (2C8, 2C9, 2D6, and 3A4) contributing to the metabolism of aficamten.Human clearance (1.1 mL/min/kg) and volume of distribution (6.5 L/kg) were predicted using 4-species allometry employing 'rule-of-exponents'. A predicted 69 hour half-life is consistent with observed half-life in human Phase-1.No CYP-based drug-drug interaction liability as a precipitant was predicted for aficamten.

Is there tree senescence? The fecundity evidence.

Despite its importance for forest regeneration, food webs, and human economies, changes in tree fecundity with tree size and age remain largely unknown. The allometric increase with tree diameter assumed in ecological models would substantially overestimate seed contributions from large trees if fecundity eventually declines with size. Current estimates are dominated by overrepresentation of small trees in regression models. We combined global fecundity data, including a substantial representation of large trees. We compared size-fecundity relationships against traditional allometric scaling with diameter and two models based on crown architecture. All allometric models fail to describe the declining rate of increase in fecundity with diameter found for 80% of 597 species in our analysis. The strong evidence of declining fecundity, beyond what can be explained by crown architectural change, is consistent with physiological decline. A downward revision of projected fecundity of large trees can improve the next generation of forest dynamic models.

Life-history parameters of adult females of Merluccius capensis (Gadidae) off the south coast of South Africa.

This study explores the life-history parameters of female Merluccius capensis off South Africa (N = 1819) during 2014-2016, including gonadosomatic index (GSI), length-at-maturity, length-weight relationships, and condition indices (relative condition [k] and Fulton's condition factor [K]). We detected weak indications of two peaks of spawning within the year, the first in austral autumn from March to May, whereas the other in austral spring around August. GSI was slightly higher in spring and autumn, though still low at all maturity stages (≤7%), though the opposite was true for the actively spawning stage (≥7%) as well as access to less such data during winter- and summertime. The length (L) at 50% maturity was around 38 cm (L50), though differences occurred between the two applied staging methods, histology and visual (macroscopic) classification, when L approached infinity. The latter method presented underestimated length at maturity values at the 75 and 95 percentiles (48 and 60 cm) compared to the corresponding percentiles given by histology (50 and 65 cm). There were trivial across-method differences in L50. However, we found a clear reduction in L50 in view of published information in prior years when this estimate was 48 (1985), 42 (2008), 53 (2011), and 24.8 (2015) cm. Overall, L explained 90% of the variation in whole body weight (W). As the bootstrapped, grand mean growth coefficient was b = 2.98, indicating a slight allometric growth function, there were no significant variations between years, though an isometric growth existed for 2016 with b = 3.0, whereas for 2014 and 2015 this b was 2.98 and 2.93, respectively. In terms of demography, females <60 cm generally showed isometric growth (b = 3) as opposed to allometric growth (b = 2.95) at >60 cm. The relative condition index (k = 1) exhibited higher values than Fulton's K, which was 0.80. Overall, the maternal stock of M. capensis along the south coast seems to be in good condition and likely spawns throughout the year, but we found that the macroscopic data tend to give biased maturity ogives.

Prediction of Human Pharmacokinetics of E0703, a Novel Radioprotective Agent, Using Physiologically Based Pharmacokinetic Modeling and an Interspecies Extrapolation Approach.

E0703, a new steroidal compound optimized from estradiol, significantly increased cell proliferation and the survival rate of KM mice and beagles after ionizing radiation. In this study, we characterize its preclinical pharmacokinetics (PK) and predict its human PK using a physiologically based pharmacokinetic (PBPK) model. The preclinical PK of E0703 was studied in mice and Rhesus monkeys. Asian human clearance (CL) values for E0703 were predicted from various allometric methods. The human PK profiles of E0703 (30 mg) were predicted by the PBPK model in Gastro Plus software 9.8 (SimulationsPlus, Lancaster, CA, USA). Furthermore, tissue distribution and the human PK profiles of different administration dosages and forms were predicted. The 0.002 L/h of CL and 0.005 L of Vss in mice were calculated and optimized from observed PK data. The plasma exposure of E0703 was availably predicted by the CL using the simple allometry (SA) method. The plasma concentration-time profiles of other dosages (20 and 40 mg) and two oral administrations (30 mg) were well-fitted to the observed values. In addition, the PK profile of target organs for E0703 exhibited a higher peak concentration (Cmax) and AUC than plasma. The developed E0703-PBPK model, which is precisely applicable to multiple species, benefits from further clinical development to predict PK in humans.

Inter-Species Pharmacokinetic Modeling and Scaling for Drug Repurposing of Pyronaridine and Artesunate.

Even though several new targets (mostly viral infection) for drug repurposing of pyronaridine and artesunate have recently emerged in vitro and in vivo, inter-species pharmacokinetic (PK) data that can extend nonclinical efficacy to humans has not been reported over 30 years of usage. Since extrapolation of animal PK data to those of humans is essential to predict clinical outcomes for drug repurposing, this study aimed to investigate inter-species PK differences in three animal species (hamster, rat, and dog) and to support clinical translation of a fixed-dose combination of pyronaridine and artesunate. PK parameters (e.g., steady-state volume of distribution (Vss), clearance (CL), area under the concentration-time curve (AUC), mean residence time (MRT), etc.) of pyronaridine, artesunate, and dihydroartemisinin (an active metabolite of artesunate) were determined by non-compartmental analysis. In addition, one- or two-compartment PK modeling was performed to support inter-species scaling. The PK models appropriately described the blood concentrations of pyronaridine, artesunate, and dihydroartemisinin in all animal species, and the estimated PK parameters in three species were integrated for inter-species allometric scaling to predict human PKs. The simple allometric equation (Y = a × Wb) well explained the relationship between PK parameters and the actual body weight of animal species. The results from the study could be used as a basis for drug repurposing and support determining the effective dosage regimen for new indications based on in vitro/in vivo efficacy data and predicted human PKs in initial clinical trials.

Neck shrivel in European plum is caused by cuticular microcracks, resulting from rapid lateral expansion of the neck late in development.

MAIN CONCLUSION: Susceptibility to neck shrivel in European plum is due to cuticular microcracking resulting from high surface area growth rates in the neck region, late in development. Susceptibility to the commercially important fruit disorder 'neck shrivel' differs among European plum cultivars. Radial cuticular microcracking occurs in the neck regions of susceptible cultivars, but not in non-susceptible ones, so would seem to be causal. However, the reason for the microcracking is unknown. The objective was to identify potential relationships between fruit growth pattern and microcracking incidence in the neck (proximal) and stylar (distal) ends of selected shrivel-susceptible and non-susceptible cultivars. Growth analysis revealed two allometric categories: The first category, the 'narrow-neck' cultivars, showed hypoallometric growth in the neck region (i.e., slower growth than in the region of maximum diameter) during early development (stages I + II). Later (during stage III) the neck region was 'filled out' by hyperallometric growth (i.e., faster than in the region of maximum diameter). The second category, the 'broad-neck' cultivars, had more symmetrical, allometric growth (all regions grew equally fast) throughout development. The narrow-neck cultivars exhibited extensive radial cuticular microcracking in the neck region, but little microcracking in the stylar region. In contrast, the broad-neck cultivars exhibited little microcracking overall, with no difference between the neck and stylar regions. Across all cultivars, a positive relationship was obtained for the level of microcracking in the neck region and the difference in allometric growth ratios between stage III and stages I + II. There were no similar relationships for the stylar region. The results demonstrate that accelerated stage III neck growth in the narrow-neck plum cultivars is associated with more microcracking and thus with more shrivel.

Is the 90-day dog study necessary for pesticide toxicity testing?

When registering a new pesticide, 90-day oral toxicity studies performed with both rodent and non-rodent species, typically rats and dogs, are part of a standard battery of animal tests required in most countries for human health risk assessment (RA). This analysis set out to determine the need for the 90-day dog study in RA by reviewing data from 195 pesticides evaluated by the US Environmental Protection Agency (USEPA) from 1998 through 2021. The dog study was used in RA for only 42 pesticides, mostly to set the point of departure (POD) for shorter-term non-dietary pesticide exposures. Dog no-observed-adverse-effect-levels (NOAELs) were lower than rat NOAELs in 90-day studies for 36 of the above 42 pesticides, suggesting that the dog was the more sensitive species. However, lower NOAELs may not necessarily correspond to greater sensitivity as factors such as dose spacing and/or allometric scaling need to be considered. Normalizing doses between rats and dogs explained the lower NOAELs in 22/36 pesticides, indicating that in those cases the dog was not more sensitive, and the comparable rat study could have been used instead for RA. For five of the remaining pesticides, other studies of appropriate duration besides the 90-day rat study were available that would have offered a similar level of protection if used to set PODs. In only nine cases could no alternative be found in the pesticide's database to use in place of the 90-day dog study for setting safe exposure levels or to identify unique hazards. The present analysis demonstrates that for most pesticide risk determinations the 90-day dog study provided no benefit beyond the rat or other available data.

First-in-Patient Dose Prediction for Adeno-Associated Virus-Mediated Hemophilia Gene Therapy Using Allometric Scaling.

In this study, the author compared the performance of two allometric scaling approaches and body-weight-based dose conversion approach for first-in-patient (FIP) dose prediction for adeno-associated virus (AAV)-mediated hemophilia gene therapy using preclinical and clinical efficacy data of nine AAV vectors. In general, body-weight-based direct conversion of effective doses in monkeys or dogs was more likely to underestimate FIP dose but worked for one bioengineered vector with a high transduction efficiency specifically in humans. In contrast, allometric scaling between gene efficiency factor (log GEF) and body weight (log W) was likely to overestimate FIP dose but worked for two vectors with capsid-specific T-cell responses in patients. The third approach, allometric scaling between log GEF and W-0.25 was appropriate for FIP dose prediction in the absence of T-cell responses to AAV vectors or a dramatic difference in vector transduction efficiency between animals and humans.

Strong positive allometry of bite force in leaf-cutter ants increases the range of cuttable plant tissues.

Atta leaf-cutter ants are the prime herbivore in the Neotropics: differently sized foragers harvest plant material to grow a fungus as a crop. Efficient foraging involves complex interactions between worker size, task preferences and plant-fungus suitability; it is, however, ultimately constrained by the ability of differently sized workers to generate forces large enough to cut vegetation. In order to quantify this ability, we measured bite forces of Atta vollenweideri leaf-cutter ants spanning more than one order of magnitude in body mass. Maximum bite force scaled almost in direct proportion to mass; the largest workers generated peak bite forces 2.5 times higher than expected from isometry. This remarkable positive allometry can be explained via a biomechanical model that links bite forces with substantial size-specific changes in the morphology of the musculoskeletal bite apparatus. In addition to these morphological changes, we show that bite forces of smaller ants peak at larger mandibular opening angles, suggesting a size-dependent physiological adaptation, probably reflecting the need to cut leaves with a thickness that corresponds to a larger fraction of the maximum possible gape. Via direct comparison of maximum bite forces with leaf mechanical properties, we demonstrate (i) that bite forces in leaf-cutter ants need to be exceptionally large compared with body mass to enable them to cut leaves; and (ii), that the positive allometry enables colonies to forage on a wider range of plant species without the need for extreme investment in even larger workers. Our results thus provide strong quantitative arguments for the adaptive value of a positively allometric bite force.

Multiple axes of visual system diversity in Ithomiini, an ecologically diverse tribe of mimetic butterflies.

The striking structural variation seen in arthropod visual systems can be explained by the overall quantity and spatio-temporal structure of light within habitats coupled with developmental and physiological constraints. However, little is currently known about how fine-scale variation in visual structures arises across shorter evolutionary and ecological scales. In this study, we characterise patterns of interspecific (between species), intraspecific (between sexes) and intraindividual (between eye regions) variation in the visual system of four ithomiine butterfly species. These species are part of a diverse 26-million-year-old Neotropical radiation where changes in mimetic colouration are associated with fine-scale shifts in ecology, such as microhabitat preference. Using a combination of selection analyses on visual opsin sequences, in vivo ophthalmoscopy, micro-computed tomography (micro-CT), immunohistochemistry, confocal microscopy and neural tracing, we quantify and describe physiological, anatomical and molecular traits involved in visual processing. Using these data, we provide evidence of substantial variation within the visual systems of Ithomiini, including: (i) relaxed selection on visual opsins, perhaps mediated by habitat preference, (ii) interspecific shifts in visual system physiology and anatomy, and (iii) extensive sexual dimorphism, including the complete absence of a butterfly-specific optic neuropil in the males of some species. We conclude that considerable visual system variation can exist within diverse insect radiations, hinting at the evolutionary lability of these systems to rapidly develop specialisations to distinct visual ecologies, with selection acting at the perceptual, processing and molecular level.