Cross-species Variation Research Articles

Cross-species variability in lobular geometry and cytochrome P450 hepatic zonation: insights into CYP1A2, CYP2D6, CYP2E1 and CYP3A4.

There is a lack of systematic research exploring cross-species variation in liver lobular geometry and zonation patterns of critical drug-metabolizing enzymes, a knowledge gap essential for translational studies. This study investigated the critical interplay between lobular geometry and key cytochrome P450 (CYP) zonation in four species: mouse, rat, pig, and human. We developed an automated pipeline based on whole slide images (WSI) of hematoxylin-eosin-stained liver sections and immunohistochemistry. This pipeline allows accurate quantification of both lobular geometry and zonation patterns of essential CYP proteins. Our analysis of CYP zonal expression shows that all CYP enzymes (besides CYP2D6 with panlobular expression) were observed in the pericentral region in all species, but with distinct differences. Comparison of normalized gradient intensity shows a high similarity between mice and humans, followed by rats. Specifically, CYP1A2 was expressed throughout the pericentral region in mice and humans, whereas it was restricted to a narrow pericentral rim in rats and showed a panlobular pattern in pigs. Similarly, CYP3A4 is present in the pericentral region, but its extent varies considerably in rats and appears panlobular in pigs. CYP2D6 zonal expression consistently shows a panlobular pattern in all species, although the intensity varies. CYP2E1 zonal expression covered the entire pericentral region with extension into the midzone in all four species, suggesting its potential for further cross-species analysis. Analysis of lobular geometry revealed an increase in lobular size with increasing species size, whereas lobular compactness was similar. Based on our results, zonated CYP expression in mice is most similar to humans. Therefore, mice appear to be the most appropriate species for drug metabolism studies unless larger species are required for other purposes, e.g., surgical reasons. CYP selection should be based on species, with CYP2E1 and CYP2D6 being the most preferable to compare four species. CYP1A2 could be considered as an additional CYP for rodent versus human comparisons, and CYP3A4 for mouse/human comparisons. In conclusion, our image analysis pipeline together with suggestions for species and CYP selection can serve to improve future cross-species and translational drug metabolism studies.

Light competition drives species replacement during secondary tropical forest succession

Light competition is thought to drive successional shifts in species dominance in closed vegetations, but few studies have assessed this for species-rich and vertically structured tropical forests. We analyzed how light competition drives species replacement during succession, and how cross-species variation in light competition strategies is determined by underlying species traits. To do so, we used chronosequence approach in which we compared 14 Mexican tropical secondary rainforest stands that differ in age (8–32 year-old). For each tree, height and stem diameter were monitored for 2 years to calculate relative biomass growth rate (RGR, the aboveground biomass gain per unit aboveground tree biomass per year). For each stand, 3D light profiles were measured to estimate individuals’ light interception to calculate light interception efficiency (LIE, intercepted light per unit biomass per year) and light use efficiency (LUE, biomass growth per intercepted light). Throughout succession, species with higher RGR attained higher changes in species dominance and thus increased their dominance over time. Both light competition strategies (LIE and LUE) increased RGR. In early succession, a high LIE and its associated traits (large crown leaf mass and low wood density) are more important for RGR. During succession, forest structure builds up, leading to lower understory light levels. In later succession, a high LUE and its associated traits (high wood density and leaf mass per area) become more important for RGR. Therefore, successional changes in relative importance of light competition strategies drive shifts in species dominance during tropical rainforest succession.

Evolutionary scaling and cognitive correlates of primate frontal cortex microstructure.

Investigating evolutionary changes in frontal cortex microstructure is crucial to understanding how modifications of neuron and axon distributions contribute to phylogenetic variation in cognition. In the present study, we characterized microstructural components of dorsolateral prefrontal cortex, orbitofrontal cortex, and primary motor cortex from 14 primate species using measurements of neuropil fraction and immunohistochemical markers for fast-spiking inhibitory interneurons, large pyramidal projection neuron subtypes, serotonergic innervation, and dopaminergic innervation. Results revealed that the rate of evolutionary change was similar across these microstructural variables, except for neuropil fraction, which evolves more slowly and displays the strongest correlation with brain size. We also found that neuropil fraction in orbitofrontal cortex layers V-VI was associated with cross-species variation in performance on experimental tasks that measure self-control. These findings provide insight into the evolutionary reorganization of the primate frontal cortex in relation to brain size scaling and its association with cognitive processes.

Pitch affects human (Homo sapiens) perception of emotional arousal from diverse animal calls.

A growing body of research demonstrates that humans can accurately perceive the emotional states of animals solely by listening to their calls, highlighting shared evolutionary ancestry. Yet, the cognitive and perceptual mechanisms underlying heterospecific emotion perception have remained open to investigation. One hypothesis is that humans rely on simple acoustic heuristics to make such judgments, for example, perceiving higher-pitched calls as reflecting heightened emotional arousal (the "pitch rule"). This could lead to accurate judgments of emotion since in most mammals, as in humans, vocal fundamental frequency (the acoustic determinant of the pitch percept) does objectively correlate with emotional arousal. In the present study, we used digital pitch manipulation to create pairs of animal calls that were perceptually identical except for pitch, and we measured human perceptions of the caller's emotional arousal using an online survey. Calls of six phylogenetically diverse species were included as stimuli. Participants attributed slightly but statistically significantly higher arousal to higher-pitched versions of the same calls. Variation in application of the pitch rule across species was not well explained by familiarity, and prior experience with cats did not significantly predict sensitivity to pitch in cat vocalizations. Cross-species variation also did not align with phylogenetic distance from humans, or the hypothetical usefulness of pitch for making accurate judgments. Thus, the pitch rule may be a "mammalomorphic" heuristic leading to accurate emotion judgments in some taxa and call types and erroneous judgments in others, depending in part on phylogenetic distance and the mechanisms of call production. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Transmission of parasitic mites (Riccardoella oudemansi) between limacid slug hosts: the role of parasite and host behaviour

Transmission between hosts is crucial to the growth, development and reproduction of many parasites. As a consequence, parasites are under selection to maximise transmission success and exhibit many behavioural and morphological adaptations that allow detection of, and movement between, hosts. However, transmission success is not determined by parasites alone, but is also shaped by host behaviours. Often, host behaviours function to minimise the risk of exposure to parasites; in some cases, however, host behaviours may be manipulated by parasites to increase transmission success. In this study, we investigated transmission of the parasitic mite Riccardoella oudemansi between slug (Limacus maculatus) hosts, considering the role of both host and parasite behaviour in determining transmission success. Host-host transmission occurred when slugs were in physical contact, but mites were also capable of moving across the substrate to locate new hosts, a process facilitated by mucus trails. We found no strong evidence that slugs avoid parasitised conspecifics, or that mites manipulate slug behaviour to increase transmission. Finally, mites showed a preference for the mucus of parasitised slugs, but did not discriminate between mucus from their own host and another parasitised slug. A general preference for mucus from parasitised slugs is likely to be important in encouraging mites to remain in close contact with their host and may also facilitate host-switching and outbreeding. We encourage further study of parasitism by Riccardoella in limacid slugs, where cross-species variation in host social behaviour may drive differences in the rate and success of parasite transmission across slug species.

Novel physiological data needed for progress in global change ecology

Studies examining the underlying causes of the distributions of species and their future trajectories under climate change have benefitted from the accumulation of measurements of thermal tolerance across the tree of life. However, gaps in the global coverage of heat-tolerance data for ectotherms persist on four critical fronts. First, most large-scale analyses treat heat tolerance as a fixed species trait despite that population-level variation can equal or exceed cross-species variation. Second, terrestrial non-arthropod invertebrates and aquatic ectotherms other than bony fish have been poorly sampled, particularly in boreal and tropical regions, the Indian Ocean and the mesopelagic-deep ocean. Third, the study of climate impacts on the heat tolerance of terrestrial ectotherms has often neglected the interaction of environmental temperatures with water availability. And fourth, the mechanisms driving the dependence of heat tolerance on oxygen supply-demand remain largely unknown. We contend that filling those data and knowledge gaps requires novel strategies for the ecophysiological sampling of the range of understudied populations and species that occupy the length of climatic gradients globally. Such developments are essential for comprehensively predicting species responses to climate change across aquatic and terrestrial biomes.

Ecological and life-history correlates of erythrocyte size and shape in Lepidosauria.

Blood oxygen‐carrying capacity is shaped both by the ambient oxygen availability as well as species‐specific oxygen demand. Erythrocytes are a critical part of oxygen transport and both their size and shape can change in relation to species‐specific life‐history, behavioural or ecological conditions. Here, we test whether components of the environment (altitude), life history (reproductive mode, body temperature) and behaviour (diving, foraging mode) drive erythrocyte size variation in the Lepidosauria (lizards, snakes and rhynchocephalians). We collected data on erythrocyte size (area) and shape (L/W: elongation ratio) from Lepidosauria across the globe (N = 235 species). Our analyses show the importance of oxygen requirements as a driver of erythrocyte size. Smaller erythrocytes were associated with the need for faster delivery (active foragers, high‐altitude species, warmer body temperatures), whereas species with greater oxygen demands (diving species, viviparous species) had larger erythrocytes. Erythrocyte size shows considerable cross‐species variation, with a range of factors linked to the oxygen delivery requirements being major drivers of these differences. A key future aspect for study would include within‐individual plasticity and how changing states, for example, pregnancy, perhaps alter the size and shape of erythrocytes in Lepidosaurs.

Wood Nutrient-Water-Density Linkages Are Influenced by Both Species and Environment.

Tropical trees store a large amount of nutrients in their woody tissues, thus triggering the question of what the functional association of these elements with other wood traits is. Given the osmotic activity of mineral elements such as potassium, sodium, and calcium, these elements should be strong candidates in mediating the water storing capacity in tropical trees. We investigated the role of wood nutrients in facilitating wood water storage in trees by using branch samples from 48 tropical tree species in South America and examined their associations with wood density (ρ). Wood density varied from 316 kg/m3 in Peru plots, where the soil nutrient status is relatively higher, to 908 kg/m3 in Brazil plots, where the nutrient availability is lower. Phosphorus content in wood varied significantly between plots with lowest values found in French Guiana (1.2 mol/m3) and plots with highest values found in Peru (43.6 mol/m3). Conversely, potassium in woody tissues showed a significant cross-species variation with Minquartia guianensis in Brazil showing the lowest values (8.8 mol/m3) and with Neea divaricata in Peru having the highest values (114 mol/m3). We found that lower wood density trees store more water in their woody tissues with cations, especially potassium, having a positive association with water storage. Specific relationships between wood cation concentrations and stem water storage potential nevertheless depend on both species’ identity and growing location. Tropical trees with increased water storage capacity show lower wood density and have an increased reliance on cations to regulate this reservoir. Our study highlights that cations play a more important role in tropical tree water relations than has previously been thought, with potassium being particularly important.

Tracing Modification to Cortical Circuits in Human and Nonhuman Primates from High-Resolution Tractography, Transcription, and Temporal Dimensions.

The neural circuits that support human cognition are a topic of enduring interest. Yet, there are limited tools available to map brain circuits in the human and nonhuman primate brain. We harnessed high-resolution diffusion MR tractography, anatomic, and transcriptomic data from individuals of either sex to investigate the evolution and development of frontal cortex circuitry. We applied machine learning to RNA sequencing data to find corresponding ages between humans and macaques and to compare the development of circuits across species. We transcriptionally defined neural circuits by testing for associations between gene expression and white matter maturation. We then considered transcriptional and structural growth to test whether frontal cortex circuit maturation is unusually extended in humans relative to other species. We also considered gene expression and high-resolution diffusion MR tractography of adult brains to test for cross-species variation in frontal cortex circuits. We found that frontal cortex circuitry development is extended in primates, and concomitant with an expansion in corticocortical pathways compared with mice in adulthood. Importantly, we found that these parameters varied relatively little across humans and studied primates. These data identify a surprising collection of conserved features in frontal cortex circuits across humans and Old World monkeys. Our work demonstrates that integrating transcriptional and structural data across temporal dimensions is a robust approach to trace the evolution of brain pathways in primates.SIGNIFICANCE STATEMENT Diffusion MR tractography is an exciting method to explore pathways, but there are uncertainties in the accuracy of reconstructed tracts. We broaden the repertoire of toolkits to enhance our ability to trace human brain pathways from diffusion MR tractography. Our integrative approach finds corresponding ages across species and transcriptionally defines neural circuits. We used this information to test for variation in circuit maturation across species and found a surprising constellation of similar features in frontal cortex neural circuits across humans and primates. Integrating across scales of biological organization expands the repertoire of tools available to study pathways in primates, which opens new avenues to study pathways in health and diseases of the human brain.

Feather growth and quality across passerines is explained by breeding rather than moulting latitude.

Tropical bird species are characterized by a comparatively slow pace of life, being predictably different from their temperate zone counterparts in their investments in growth, survival and reproduction. In birds, the development of functional plumage is often considered energetically demanding investment, with consequences on individual fitness and survival. However, current knowledge of interspecific variation in feather growth patterns is mostly based on species of the northern temperate zone. We evaluated patterns in tail feather growth rates (FGR) and feather quality (stress-induced fault bar occurrence; FBO), using 1518 individuals of 167 species and 39 passerine families inhabiting Afrotropical and northern temperate zones. We detected a clear difference in feather traits between species breeding in the temperate and tropical zones, with the latter having significantly slower FGR and three times higher FBO. Moreover, trans-Saharan latitudinal migrants resembled temperate zone residents in that they exhibited a comparatively fast FGR and low FBO, despite sharing moulting environments with tropical species. Our results reveal convergent latitudinal shifts in feather growth investments (latitudinal syndrome) across unrelated passerine families and underscore the importance of breeding latitude in determining cross-species variation in key avian life-history traits.

Comparison of human and faunal enamel isotopes reveals diverse paleodiet and exchange patterns at the highland Maya Site of Kaminaljuyu, Guatemala

This study provides an isotopic examination of both human and animal paleodiets and mobility patterns at a highland Maya community. Kaminaljuyu, Guatemala, was a large Prehispanic center located in a distinctly cooler, drier setting compared with the majority of Maya sites in the surrounding lowlands. Previous archaeological research at Kaminaljuyu revealed it played an important political and economic role in the Maya region, assisting in the obsidian trade network and maintaining ties with communities as far away as Teotihuacan in central Mexico. By examining the strontium (87Sr/86Sr), carbon (δ13C), and oxygen (δ18O) isotope values from dental enamel of humans and terrestrial mammals at the site, this study provides direct evidence of long-distance animal trade, explores the nature and timing of such activities, and compares highland dietary patterns with faunal studies in the lowlands. Our results indicate that isotopically non-local humans and animals are most frequently found in special and ceremonial contexts, indicating that long-distance movements of people and products were motivated for politically or ritually significant events. Although dietary patterns showed cross-species variation, diets within species were similar between highland and lowland settings.

Decoding the effects of synonymous variants.

Synonymous single nucleotide variants (sSNVs) are common in the human genome but are often overlooked. However, sSNVs can have significant biological impact and may lead to disease. Existing computational methods for evaluating the effect of sSNVs suffer from the lack of gold-standard training/evaluation data and exhibit over-reliance on sequence conservation signals. We developed synVep (synonymous Variant effect predictor), a machine learning-based method that overcomes both of these limitations. Our training data was a combination of variants reported by gnomAD (observed) and those unreported, but possible in the human genome (generated). We used positive-unlabeled learning to purify the generated variant set of any likely unobservable variants. We then trained two sequential extreme gradient boosting models to identify subsets of the remaining variants putatively enriched and depleted in effect. Our method attained 90% precision/recall on a previously unseen set of variants. Furthermore, although synVep does not explicitly use conservation, its scores correlated with evolutionary distances between orthologs in cross-species variation analysis. synVep was also able to differentiate pathogenic vs. benign variants, as well as splice-site disrupting variants (SDV) vs. non-SDVs. Thus, synVep provides an important improvement in annotation of sSNVs, allowing users to focus on variants that most likely harbor effects.

Contemporary spatial extent and environmental drivers of larval coregonine distributions across Lake Ontario

Coregonine fishes are important to Laurentian Great Lakes food webs and fisheries and are central to basin-wide conservation initiatives. In Lake Ontario, binational management objectives include conserving and restoring spawning stocks of cisco (Coregonus artedi) and lake whitefish (C. clupeaformis), but the spatial extent of contemporary coregonine spawning habitat and the environmental factors regulating early life success are not well characterized. In Spring 2018, we conducted a binational ichthyoplankton assessment to describe the spatial extent of coregonine spawning habitat across Lake Ontario. We then quantified the relative importance of a suite of biophysical variables hypothesized to influence coregonine early life success using generalized additive mixed models and multimodel inference. Between April 10 and May 14, we conducted 1,092 ichthyoplankton tows and captured 2,350+ coregonine larvae across 17 sampling areas, predominantly within embayments. Although 95% of catches were in the eastern basin, coregonine larvae were also found in historical south shore spawning areas. Most coregonine larvae were cisco; <6% were lake whitefish. Observed catches of both species across sampling areas were strongly and similarly associated with ice cover duration, but the importance of site-specific characteristics varied, such as distance to shore and site depth for cisco and lake whitefish, respectively. These results suggest that regional-scale climatic drivers and local environmental habitat characteristics interact to regulate early life stage success. Furthermore, strong regional and cross-species variation in larval distributions emphasize the importance of lake-wide assessments for monitoring both the current eastern basin populations and potential expansions into western Lake Ontario habitats.

A new model of myofibroblast-cardiomyocyte interactions and their differences across species

Although coupling between cardiomyocytes and myofibroblasts is well known to affect the physiology and pathophysiology of cardiac tissues across species, relating these observations to humans is challenging because the effect of this coupling varies across species and because the sources of these effects are not known. To identify the sources of cross-species variation, we built upon previous mathematical models of myofibroblast electrophysiology and developed a mechanoelectrical model of cardiomyocyte-myofibroblast interactions as mediated by electrotonic coupling and transforming growth factor-β1. The model, as verified by experimental data from the literature, predicted that both electrotonic coupling and transforming growth factor-β1 interaction between myocytes and myofibroblast prolonged action potential in rat myocytes but shortened action potential in human myocytes. This variance could be explained by differences in the transient outward K+ current associated with differential Kv4.2 gene expression across species. Results are useful for efforts to extrapolate the results of animal models to the predicted effects in humans and point to potential therapeutic targets for fibrotic cardiomyopathy.

Correlated Evolution of Acrobatic Display and Both Neural and Somatic Phenotypic Traits in Manakins (Pipridae).

Brightly colored manakin (Aves: Pipridae) males are known for performing acrobatic displays punctuated by non-vocal sounds (sonations) in order to attract dull colored females. The complexity of the display sequence and assortment of display elements involved (e.g., sonations, acrobatic maneuvers, and cooperative performances) varies considerably across manakin species. Species-specific display elements coevolve with display-distinct specializations of the neuroanatomical, muscular, endocrine, cardiovascular, and skeletal systems in the handful of species studied. Conducting a broader comparative study, we previously found positive associations between display complexity and both brain mass and body mass across eight manakin genera, indicating selection for neural and somatic expansion to accommodate display elaboration. Whether this gross morphological variation is due to overall brain and body mass expansion (concerted evolution) versus size increases in only functionally relevant brain regions and growth of particular body ("somatic") features (mosaic evolution) remains to be explored. Here, we test the hypothesis that cross-species variation in male brain mass and body mass is driven by mosaic evolution. We predicted positive associations between display complexity and variation in the volume of the cerebellum and sensorimotor arcopallium, brain regions which have roles in sensorimotor processes, and learning and performance of precisely timed and sequenced thoughts and movements, respectively. In contrast, we predicted no associations between the volume of a limbic arcopallial nucleus or a visual thalamic nucleus and display complexity as these regions have no-specific functional relationship to display behavior. For somatic features, we predicted that the relationship between body mass and complexity would not include contributions of tarsus length based on a recent study suggesting selection on tarsus length is less labile than body mass. We tested our hypotheses in males from 12 manakin species and a closely related flycatcher. Our analyses support mosaic evolution of neural and somatic features functionally relevant to display and indicate that sexual selection for acrobatic complexity increases the capacity for procedural learning via cerebellar enlargement and may decrease maneuverability via increases in tarsus length.

Tracing the evolution of cortical circuits in humans from ultra‐high resolution connectomic, transcriptomic, and temporal dimensions

How neural circuits supporting human cognition evolved is a topic of enduring interest. The lack of tools available to map human brain circuits has precluded our ability to map the human connectome and trace its evolution. Here, we harness ultra-high resolution connectomic, anatomic, and transcriptomic variation to investigate the evolution and development of frontal cortex circuitry in humans. We align temporal trajectories in gene expression to identify equivalent ages across humans, macaques, and mice during postnatal development. We use these data to test for cross-species variation in developmental programs leading to modifications in adult neural circuits. We test for cross-species variation in temporal and spatial expression of genes linked to long-range projections across the frontal cortex (i.e., “supragranular-enriched genes”). We also compare the growth and pathway types coursing through the frontal cortex of mice, macaques, and humans with structural and high resolution diffusion MR tractography. We find that compared with that of mice, frontal cortex circuitry development is protracted in primates and is concomitant with an expansion of cortico-cortical projections in adulthood. We also find very little variation in these parameters among studied primates. For instance, an analysis of variance on the proportion of cortico-cortical pathways shows major differences across the three species (F=19.11; p<0.05; n=17) but post hoc Tukey tests show no differences between humans and macaques (p>0.05). These data together identify a collection of conserved features in frontal cortex circuitry of humans and Old World monkeys. Our work is the first to demonstrate that integrating transcriptional and connectomic data across temporal dimensions in primates is a robust approach to trace the evolution of human brain connectomics.

Patterns and processes of pathogen exposure in gray wolves across North America

The presence of many pathogens varies in a predictable manner with latitude, with infections decreasing from the equator towards the poles. We investigated the geographic trends of pathogens infecting a widely distributed carnivore: the gray wolf (Canis lupus). Specifically, we investigated which variables best explain and predict geographic trends in seroprevalence across North American wolf populations and the implications of the underlying mechanisms. We compiled a large serological dataset of nearly 2000 wolves from 17 study areas, spanning 80° longitude and 50° latitude. Generalized linear mixed models were constructed to predict the probability of seropositivity of four important pathogens: canine adenovirus, herpesvirus, parvovirus, and distemper virus—and two parasites: Neospora caninum and Toxoplasma gondii. Canine adenovirus and herpesvirus were the most widely distributed pathogens, whereas N. caninum was relatively uncommon. Canine parvovirus and distemper had high annual variation, with western populations experiencing more frequent outbreaks than eastern populations. Seroprevalence of all infections increased as wolves aged, and denser wolf populations had a greater risk of exposure. Probability of exposure was positively correlated with human density, suggesting that dogs and synanthropic animals may be important pathogen reservoirs. Pathogen exposure did not appear to follow a latitudinal gradient, with the exception of N. caninum. Instead, clustered study areas were more similar: wolves from the Great Lakes region had lower odds of exposure to the viruses, but higher odds of exposure to N. caninum and T. gondii; the opposite was true for wolves from the central Rocky Mountains. Overall, mechanistic predictors were more informative of seroprevalence trends than latitude and longitude. Individual host characteristics as well as inherent features of ecosystems determined pathogen exposure risk on a large scale. This work emphasizes the importance of biogeographic wildlife surveillance, and we expound upon avenues of future research of cross-species transmission, spillover, and spatial variation in pathogen infection.

Trait-density-microsite interactions indicate plastic and non-plastic germination strategies of co-occurring desert annual plants

Functional traits have been linked to relevant vital rates across co-occurring species, such as growth and survival. However, the relationship between plant traits and germination has been much less studied, despite that germination can be a key transition for plants. Building on evolutionary theory, we propose that variation in germination fraction across co-occurring desert annual plants may result from the interaction of post-germination plant traits, density dependence and microsite type. Our study system consisted of three summer annual species abundant in a desert in western Argentina, for which we quantified germination fractions in three microsite types: Larrea divaricata shrub, Bulnesia retama shrub, and open spaces among shrubs. Based on post-germination trait data (summarized by a principal component, PC1), the annual species can be arranged in terms of increasing stress-tolerance, from Amaranthus standleyanus, to Gomphrena martiana and Tribulus terrestris. We found an interaction between PC1 and density of conspecific seeds suggesting that the strength of plastic negative density-dependence decreased with the increase of plant stress-tolerance. Our results emphasize that both plastic and non-plastic (bet-hedging) mechanisms would contribute to shape germination dynamics across annual plants, and that plant traits can offer parsimonious explanations for such cross-species variation.

Outbreak of Encephalitis Caused by Human Herpesvirus Type 1 (HSV-1) in NonHuman Captive Primates in São Paulo, SP, Brazil

Human herpesvirus type 1 (HSV-1), a Alphaherpesvirinae, has a broad range of cross-species infectivity with considerable variation in expression and disease severity among different hosts. Infection in humans, results in mild disease characterized by mucocutaneous lesions. In some species of nonhuman primates, however, the infection can be lethal. Transmission occurs through food contaminated by humans with labial herpes, offered to monkeys, constituting an important anthropozoonosis. In this study, we describe the occurrence of two outbreaks of encephalitis caused by HSV-1, occurring in the State of São Paulo, Brazil. The first outbreak affected a Brown howler monkey and three marmosets. The Brown howler monkey had tongue ulcers and enteritis and the marmosets were found dead without presenting clinical symptomatology. The second outbreak affected ten marmosets that were found dead suddenly in the enclosure without presenting symptoms or clinical signs. Organ fragments were processed for transmission electron microscopy, histopathology and inoculation in cell culture techniques. Ballooning degeneration, foci of monolymphocytic inflammatory reaction, corpuscle of eosinophilic inclusion, monolymphocytic meningitis and desquamative monolymphocytic enterocolitis, were the main lesions observed by histopathology. By the negative staining technique, enveloped and non-enveloped, herpesvirus particles were found, measuring 120-200 nm in diameter in all samples of organ fragments. The presence of aggregates formed by antigenantibody complex, characterized the positive result obtained in the immunoelectron microscopy technique for HSV-1. Using the immunocytochemistry technique, the antigen-antibody interaction was strongly enhanced by the colloidal gold particles over the herpesvirus, confirming the presence of HSV-1. Intranuclear incomplete particles measuring 80-100 nm in diameter and complete or enveloped scattered in the cytoplasm, were visualized in ultrathin sections of liver and cell culture measuring 140 nm of diameter. Immature particles budding from cell membranes were also observed. In viral isolation in VERO cells, typical cytopathic effect was observed in brain samples.

Variation of the adaptive substitution rate between species and within genomes

The importance of adaptive mutations in molecular evolution is extensively debated. Recent developments in population genomics allow inferring rates of adaptive mutations by fitting a distribution of fitness effects to the observed patterns of polymorphism and divergence at sites under selection and sites assumed to evolve neutrally. Here, we summarize the current state-of-the-art of these methods and review the factors that affect the molecular rate of adaptation. Several studies have reported extensive cross-species variation in the proportion of adaptive amino-acid substitutions (α) and predicted that species with larger effective population sizes undergo less genetic drift and higher rates of adaptation. Disentangling the rates of positive and negative selection, however, revealed that mutations with deleterious effects are the main driver of this population size effect and that adaptive substitution rates vary comparatively little across species. Conversely, rates of adaptive substitution have been documented to vary substantially within genomes. On a genome-wide scale, gene density, recombination and mutation rate were observed to play a role in shaping molecular rates of adaptation, as predicted under models of linked selection. At the gene level, it has been reported that the gene functional category and the macromolecular structure substantially impact the rate of adaptive mutations. Here, we deliver a comprehensive review of methods used to infer the molecular adaptive rate, the potential drivers of adaptive evolution and how positive selection shapes molecular evolution within genes, across genes within species and between species.