Highland deer mice support increased thermogenesis in response to chronic cold hypoxia by shifting uptake of circulating fatty acids from muscles to brown adipose tissue.

During maximal cold challenge (cold-induced V̇O2,max) in hypoxia, highland deer mice (Peromyscus maniculatus) show higher rates of circulatory fatty acid delivery compared with lowland deer mice. Fatty acid delivery also increases with acclimation to cold hypoxia (CH) and probably plays a major role in supporting the high rates of thermogenesis observed in highland deer mice. However, it is unknown which tissues take up these fatty acids and their relative contribution to thermogenesis. The goal of this study was to determine the uptake of circulating fatty acids into 24 different tissues during hypoxic cold-induced V̇O2,max, by using [1-14C]2-bromopalmitic acid. To uncover evolved and environment-induced changes in fatty acid uptake, we compared lab-born and -raised highland and lowland deer mice, acclimated to either thermoneutral (30°C, 21 kPa O2) or CH (5°C, 12 kPa O2) conditions. During hypoxic cold-induced V̇O2,max, CH-acclimated highlanders decreased muscle fatty acid uptake and increased uptake into brown adipose tissue (BAT) relative to thermoneutral highlanders, a response that was absent in lowlanders. CH acclimation was also associated with increased activities of enzymes citrate synthase and ß-hydroxyacyl-CoA dehydrogenase in the BAT of highlanders, and higher levels of fatty acid translocase CD36 (FAT/CD36) in both populations. This is the first study to show that cold-induced fatty acid uptake is distributed across a wide range of tissues. Highland deer mice show plasticity in this fatty acid distribution in response to chronic cold hypoxia, and combined with higher rates of tissue delivery, this contributes to their survival in the cold high alpine environment.

Microbiome diversity and zoonotic bacterial pathogen prevalence in Peromyscus mice from agricultural landscapes and synanthropic habitat.

Rodents are key reservoirs of zoonotic pathogens and play an important role in disease transmission to humans. Importantly, anthropogenic land-use change has been found to increase the abundance of rodents that thrive in human-built environments (synanthropic rodents), particularly rodent reservoirs of zoonotic disease. Anthropogenic environments also affect the microbiome of synanthropic wildlife, influencing wildlife health and potentially introducing novel pathogens. Our objective was to examine the effect of agricultural development and synanthropic habitat on microbiome diversity and the prevalence of zoonotic bacterial pathogens in wild Peromyscus mice to better understand the role of these rodents in pathogen maintenance and transmission. We conducted 16S amplicon sequencing on faecal samples using long-read nanopore sequencing technology to characterize the rodent microbiome. We compared microbiome diversity and composition between forest and synanthropic habitats in agricultural and undeveloped landscapes and screened for putative pathogenic bacteria. Microbiome richness, diversity, and evenness were higher in the agricultural landscape and synanthropic habitat compared to undeveloped-forest habitat. Microbiome composition also differed significantly between agricultural and undeveloped landscapes and forest and synanthropic habitats. We detected overall low diversity and abundance of putative pathogenic bacteria, though putative pathogens were more likely to be found in mice from the agricultural landscape. Our findings show that landscape- and habitat-level anthropogenic factors affect Peromyscus microbiomes and suggest that landscape-level agricultural development may be important to predict zoonotic pathogen prevalence. Ultimately, understanding how anthropogenic land-use change and synanthropy affect rodent microbiomes and pathogen prevalence is important to managing transmission of rodent-borne zoonotic diseases to humans.

Large nesting expression in deer mice remains stable under conditions of visual deprivation despite heightened limbic involvement: Perspectives on compulsive-like behavior.

Visual stimuli and limbic activation varyingly influence obsessive-compulsive symptom expression and so impact treatment outcomes. Some symptom phenotypes, for example, covert repugnant thoughts, are likely less sensitive to sensory stimuli compared to symptoms with an extrinsic focus, that is, symptoms related to contamination, safety, and "just-right-perceptions." Toward an improved understanding of the neurocognitive underpinnings of obsessive-compulsive psychobiology, work in naturalistic animal model systems is useful. Here, we explored the impact of visual feedback and limbic processes on 24 normal (NNB) and large (LNB) nesting deer mice, respectively (as far as possible, equally distributed between sexes). Briefly, after behavioral classification into either the NNB or LNB cohorts, mice of each cohort were separated into two groups each and assessed for nesting expression under either standard light conditions or conditions of complete visual deprivation (VD). Nesting outcomes were assessed in terms of size and neatness. After nesting assessment completion, mice were euthanized, and samples of frontal-cortical and hippocampal tissues were collected to determine serotonin and noradrenaline concentrations. Our results show that LNB, as opposed to NNB, represents an inflexible and excessive behavioral phenotype that is not dependent on visually guided action-outcome processing, and that it associates with increased frontal-cortical and hippocampal noradrenaline concentrations, irrespective of lighting condition. Collectively, the current results are informing of the neurocognitive underpinnings of nesting behavior. It also provides a valuable foundation for continued investigations into the noradrenergic mechanisms that may influence the development and promulgation of excessive, rigid, and inflexible behaviors.

Evolved changes in phenotype across skeletal muscles in deer mice native to high altitude.

The cold and hypoxic conditions at high altitude necessitate high metabolic O2 demands to support thermogenesis while hypoxia reduces O2 availability. Skeletal muscles play key roles in thermogenesis, but our appreciation of muscle plasticity and adaptation at high altitude has been hindered by past emphasis on only a small number of muscles. We examined this issue in deer mice (Peromyscus maniculatus). Mice derived from both high-altitude and low-altitude populations were born and raised in captivity and then acclimated as adults to normoxia or hypobaric hypoxia (12 kPa O2 for 6-8 wk). Maximal activities of citrate synthase (CS), cytochrome c oxidase (COX), ß-hydroxyacyl-CoA dehydrogenase (HOAD), hexokinase (HK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) were measured in 20 muscles involved in shivering, locomotion, body posture, ventilation, and mastication. Principal components analysis revealed an overall difference in muscle phenotype between populations but no effect of hypoxia acclimation. High-altitude mice had greater activities of mitochondrial enzymes and/or lower activities of PK or LDH across many (but not all) respiratory, limb, core and mastication muscles compared with low-altitude mice. In contrast, chronic hypoxia had very few effects across muscles. Further examination of CS in the gastrocnemius showed that population differences in enzyme activity stemmed from differences in protein abundance and mRNA expression but not from population differences in CS amino acid sequence. Overall, our results suggest that evolved increases in oxidative capacity across many skeletal muscles, at least partially driven by differences in transcriptional regulation, may contribute to high-altitude adaptation in deer mice.NEW & NOTEWORTHY Most previous studies of muscle plasticity and adaptation in high-altitude environments have focused on a very limited number of skeletal muscles. Comparing high-altitude versus low-altitude populations of deer mice, we show that a large number of muscles involved in shivering, locomotion, body posture, ventilation, and mastication exhibit greater mitochondrial enzyme activities in the high-altitude population. Therefore, evolved increases in mitochondrial oxidative capacity across skeletal muscles contribute to high-altitude adaptation.

Adaptive tail-length evolution in deer mice is associated with differential Hoxd13 expression in early development.

Variation in the size and number of axial segments underlies much of the diversity in animal body plans. Here we investigate the evolutionary, genetic and developmental mechanisms driving tail-length differences between forest and prairie ecotypes of deer mice (Peromyscus maniculatus). We first show that long-tailed forest mice perform better in an arboreal locomotion assay, consistent with tails being important for balance during climbing. We then identify six genomic regions that contribute to differences in tail length, three of which associate with caudal vertebra length and the other three with vertebra number. For all six loci, the forest allele increases tail length, indicative of the cumulative effect of natural selection. Two of the genomic regions associated with variation in vertebra number contain Hox gene clusters. Of those, we find an allele-specific decrease in Hoxd13 expression in the embryonic tail bud of long-tailed forest mice, consistent with its role in axial elongation. Additionally, we find that forest embryos have more presomitic mesoderm than prairie embryos and that this correlates with an increase in the number of neuromesodermal progenitors, which are modulated by Hox13 paralogues. Together, these results suggest a role for Hoxd13 in the development of natural variation in adaptive morphology on a microevolutionary timescale.

Higher offspring mortality in deer mice (Peromyscus maniculatus bairdii) that spontaneously present with large nest building behaviour.

Nesting is a normal, evolutionary conserved rodent behavioural phenotype that is expressed for purposes of breeding, safety, and thermal regulation. Further, nesting is commonly assessed as marker of overall rodent health and wellbeing, with poorer nesting performance generally proposed to resemble a worse state of health. Deer mice can be bidirectionally separated with 30 % of mice presenting with excessively large nesting behaviour (LNB). All laboratory-housed deer mice are exposed to identical environmental conditions. Thus, the functional purpose of LNB remains unknown. Considering the evolutionary functions of nesting, we hypothesized that LNB will be related to an inflated drive to breed and nurse offspring. After breeding two generations of offspring from six 'normal' nesting (NNB) and seven LNB expressing pairs, our data showed that while as fertile as NNB expressing pairs, offspring survival of LNB mice were notably worse (67.9 % vs. 98.3 %). In conclusion, variance in nesting behaviour should be considered when animal health and wellbeing is considered, since it may point to underlying biobehavioural perturbations.

Anatomy and mechanisms of vocal production in harvest mice.

Characterizing mechanisms of vocal production provides important insight into the ecology of acoustic divergence. In this study, we characterized production mechanisms of two types of vocalizations emitted by western harvest mice (Reithrodontomys megalotis), a species uniquely positioned to inform trait evolution because it is a sister taxon to peromyscines (Peromyscus and Onychomys spp.), which use vocal fold vibrations to produce long-distance calls, but more ecologically and acoustically similar to baiomyines (Baiomys and Scotinomys spp.), which employ a whistle mechanism. We found that long-distance calls (∼10 kHz) were produced by airflow-induced vocal fold vibrations, whereas high-frequency quavers used in close-distance social interactions (∼80 kHz) were generated by a whistle mechanism. Both production mechanisms were facilitated by a characteristic laryngeal morphology. Our findings indicate that the use of vocal fold vibrations for long-distance communication is widespread in reithrodontomyines (Onychomys, Peromyscus, Reithrodontomys spp.) despite overlap in frequency content that characterizes baiomyine whistled vocalizations. The results illustrate how different production mechanisms shape acoustic variation in rodents and contribute to ecologically relevant communication distances.

Leveraging the unique social organization of California mice to study circuit-specific effects of oxytocin on behavior.

Oxytocin is a versatile neuropeptide that modulates many different forms of social behavior. Recent hypotheses pose that oxytocin enhances the salience of rewarding and aversive social experiences, and the field has been working to identify mechanisms that allow oxytocin to have diverse effects on behavior. Here we review studies conducted on the California mouse (Peromyscus californicus) that shed light on how oxytocin modulates social behavior following stressful experiences. In this species, both males and females exhibit high levels of aggression, which has facilitated the study of how social stress impacts both sexes. We review findings of short- and long-term effects of social stress on the reactivity of oxytocin neurons. We also consider the results of pharmacological studies which show that oxytocin receptors in the bed nucleus of the stria terminalis and nucleus accumbens have distinct but overlapping effects on social approach behaviors. These findings help explain how social stress can have different behavioral effects in males and females, and how oxytocin can have such divergent effects on behavior. Finally, we consider how new technological developments and innovative research programs take advantage of the unique social organization of California mice to address questions that can be difficult to study in conventional rodent model species. These new methods and questions have opened new avenues for studying the neurobiology of social behavior.

Adaptation in brain structure and respiratory and olfactory structures across environmental gradients in African and North American muroid rodents.

Morphometric studies of 3D micro CT-scanned images can provide insights into the evolution of the brain and sensory structures but such data are still scarce for the most diverse mammalian order of rodents. From reviewed and new data, we tested for convergence to extreme aridity and high elevation in the sensory and brain morphology of rodents, from morphometric data from micro-CT X-ray scans of 174 crania of 16 species of three distantly related African murid (soft-furred mice, Praomyini, laminate-toothed rats, Otomyini, and gerbils, Gerbillinae) clades and one North American cricetid (deer mice and white-footed mice, Peromyscus) clade. Recent studies demonstrated convergent evolution acting on the oval window area of the cochlea (enlarged in extremely arid-adapted species of Otomyini and Gerbillinae) and on endocranial volume (reduced in high elevation taxa of Otomyini and Peromyscus). However, contrary to our predictions, we did not find evidence of convergence in brain structure to aridity, or in the olfactory/respiratory system (turbinate bones) to high elevation. Brain structure differed, particularly in the petrosal lobules of the cerebellum and the olfactory bulbs, between Otomyini and Gerbillinae, with extreme arid-adapted species in each clade being highly divergent (not convergent) from other species in the same clade. We observed greater "packing" of the maxillary turbinate bones, which have important respiratory functions, in Peromyscus mice from high and low elevations compared to the high-elevation African Praomyini, but more complex patterns within Peromyscus, probably related to trade-offs in respiratory physiology and heat exchange in the nasal epithelium associated with high-elevation adaptation.

Differential burdens of blacklegged ticks (Ixodes scapularis) on sympatric rodent hosts.

In the United States, there has been a steady increase in diagnosed cases of tick-borne diseases in people, most notably Lyme disease. The pathogen that causes Lyme disease, Borrelia burgdorferi, is transmitted by the blacklegged tick (Ixodes scapularis). Several small mammals are considered key reservoirs of this pathogen and are frequently-used hosts by blacklegged ticks. However, limited studies have evaluated between-species host use by ticks. This study compared I. scapularis burdens and tick-associated pathogen presence in wild-caught Clethrionomys gapperi (southern red-backed voles) and Peromyscus spp. (white-footed mice) in forested areas where the habitat of both species overlapped. Rodent trapping data collected over two summers showed a significant difference in the average tick burden between species. Adult Peromyscus spp. had an overall mean of 4.03 ticks per capture, while adult C. gapperi had a mean of 0.47 ticks per capture. There was a significant association between B. burgdorferi infection and host species with more Peromyscus spp. positive samples than C. gapperi (65.8% and 10.2%, respectively). This work confirms significant differences in tick-host use and pathogen presence between sympatric rodent species. It is critical to understand tick-host interactions and tick distributions to develop effective and efficient tick control methods.

Pair bonding and disruption impact lung transcriptome in monogamous Peromyscus californicus.

Social interactions affect physiological and pathological processes, yet their direct impact in peripheral tissues remains elusive. Recently we showed that disruption of pair bonds in monogamous Peromyscus californicus promotes lung tumorigenesis, pointing to a direct effect of bonding status in the periphery (Naderi et al., 2021). Here we show that lung transcriptomes of tumor-free Peromyscus are altered in a manner that depends on pair bonding and superseding the impact of genetic relevance between siblings. Pathways affected involve response to hypoxia and heart development. These effects are consistent with the profile of the serum proteome of bonded and bond-disrupted Peromyscus and were extended to lung cancer cells cultured in vitro, with sera from animals that differ in bonding experiences. In this setting, the species' origin of serum (deer mouse vs FBS) is the most potent discriminator of RNA expression profiles, followed by bonding status. By analyzing the transcriptomes of lung cancer cells exposed to deer mouse sera, an expression signature was developed that discriminates cells according to the history of social interactions and possesses prognostic significance when applied to primary human lung cancers. The results suggest that present and past social experiences modulate the expression profile of peripheral tissues such as the lungs, in a manner that impacts physiological processes and may affect disease outcomes. Furthermore, they show that besides the direct effects of the hormones that regulate bonding behavior, physiological changes influencing oxygen metabolism may contribute to the adverse effects of bond disruption.

When the tap runs dry: the physiological effects of acute experimental dehydration in Peromyscus eremicus.

Desert organisms have evolved physiological, biochemical and genomic mechanisms to survive the extreme aridity of desert environments. Studying desert-adapted species provides a unique opportunity to investigate the survival strategies employed by organisms in some of the harshest habitats on Earth. Two of the primary challenges faced in desert environments are maintaining water balance and thermoregulation. We collected data in a simulated desert environment and a captive colony of cactus mice (Peromyscus eremicus) and used lab-based experiments with real time physiological measurements; energy expenditure, water loss rate and respiratory exchange rate, to characterize the response to water deprivation. Mice without access to water had significantly lower energy expenditures and in turn, reduced water loss compared to mice with access to water after the first 24 h of the experiment. Additionally, we observed significant mass loss that is probably due to dehydration-associated anorexia a response to limit fluid loss by reducing waste and the solute load as well as allowing water reabsorption from the kidneys and gastrointestinal tract. Finally, we observed body temperature correlated with sex, with males without access to water maintaining body temperature when compared with hydrated males, whereas body temperature decreased for females without access to water, suggesting daily metabolic depression in females.

Everglades virus: an underrecognized disease-causing subtype of Venezuelan equine encephalitis virus endemic to Florida, USA.

Everglades virus (EVEV) is subtype II of the Venezuelan equine encephalitis virus (VEEV) complex (Togaviridae: Alphavirus), endemic to Florida, USA. EVEV belongs to a clade that includes both enzootic and epizootic/epidemic VEEV subtypes. Like other enzootic VEEV subtypes, muroid rodents are important vertebrate hosts for EVEV and certain mosquitoes are important vectors. The hispid cotton rat Sigmodon hispidus and cotton mouse Peromyscus gossypinus are important EVEV hosts, based on natural infection (virus isolation and high seropositivity), host competence (experimental infections), and frequency of contact with the vector. The mosquito Culex (Melanoconion) cecedei is the only confirmed vector of EVEV based upon high natural infection rates, efficient vector competence, and frequent feeding upon muroid rodents. Human disease attributed to EVEV is considered rare. However, cases of meningitis and encephalitis are recorded from multiple sites, separated by 250 km or more. Phylogenetic analyses indicate that EVEV is evolving, possibly due to changes in the mammal community. Mutations in the EVEV genome are of concern, given that epidemic strains of VEEV (subtypes IAB and IC) are derived from enzootic subtype ID, the closest genetic relative of EVEV. Should epizootic mutations arise in EVEV, the abundance of Aedes taeniorhynchus and other epizootic VEEV vectors in southern Florida provides a conducive environment for widespread transmission. Other factors that will likely influence the distribution and frequency of EVEV transmission include the establishment of Culex panocossa in Florida, Everglades restoration, mammal community decline due to the Burmese python, land use alteration by humans, and climate change.

Zoonotic implications of white-footed mice habitat selection and territoriality in fragmented landscapes.

White-footed mouse (Peromyscus leucopus) populations can thrive in fragmented suburban and urban parks and residential spaces and play a pivotal role in the spread and prevalence of tick-borne diseases. We collected spatial data on 58 individual mice living at the intersection of county park land and residential land in suburban Howard County, MD, U.S.A. We analyzed mouse density, home-range size and overlap, and a Bayesian mixed-effects model to identify the habitats where they were found relative to where they were caught, as well as a resource selection function for general habitat use. We found that as mouse density increased, home-range size decreased. The overlap indices and the resource selection function supported territoriality coupled with site-specific space use in these suburban mouse populations. While mice occurred in open areas, forest edge, and forest, they showed a strong preference for forested areas. Interestingly, mice captured only 30 to 40 m into the forest rarely used the nearby private yards or human structures and this has direct implications for the placement of rodent-targeted tick control treatments. Our study supports the need for zoonotic disease management frameworks that are based on site-specific land cover characteristics as well as specific management objectives.

It's about time: small mammal communities and Lyme disease emergence.

Theory predicts that biodiversity changes due to climate warming can mediate the rate of disease emergence. The mechanisms linking biodiversity-disease relationships have been described both theoretically and empirically but remain poorly understood. We investigated the relations between host diversity and abundance and Lyme disease risk in southern Quebec, a region where Lyme disease is rapidly emerging. We found that both the abundance of small mammal hosts and the relative abundance of the tick's natural host, the white-footed mouse (Peromyscus leucopus), influenced measures of disease risk in tick vectors (Borrelia burgdorferi infection abundance and prevalence in tick vectors). Our results suggest that the increase in Lyme disease risk is modulated by regional processes involving the abundance and composition of small mammal assemblages. However, the nature and strength of these relationships was dependent both on time and geographic area. The strong effect of P. leucopus abundance on disease risk we report here is of significant concern, as this competent host is predicted to increase in abundance and occurrence in the region, with the northern shift in the range of North American species under climate warming.

Omnivore diet composition alters parasite resistance and host condition.

Diet composition modulates animals' ability to resist parasites and recover from stress. Broader diet breadths enable omnivores to mount dynamic responses to parasite attack, but little is known about how plant/prey mixing might influence responses to infection. Using omnivorous deer mice (Peromyscus maniculatus) as a model, we examine how varying plant and prey concentrations in blended diets influence resistance and body condition following infestation by Rocky Mountain wood ticks (Dermacentor andersoni). In two repeated experiments, deer mice fed for 4 weeks on controlled diets that varied in proportions of seeds and insects were then challenged with 50 tick larvae in two sequential infestations. The numbers of ticks successfully feeding on mice declined by 25% and 66% after the first infestation (in the first and second experiments, respectively), reflecting a pattern of acquired resistance, and resistance was strongest when plant/prey ratios were more equally balanced in mouse diets, relative to seed-dominated diets. Diet also dramatically impacted the capacity of mice to cope with tick infestations. Mice fed insect-rich diets lost 15% of their body weight when parasitized by ticks, while mice fed seed-rich diets lost no weight at all. While mounting/maintaining an immune response may be energetically demanding, mice may compensate for parasitism with fat and carbohydrate-rich diets. Altogether, these results suggest that a diverse nutritional landscape may be key in enabling omnivores' resistance and resilience to infection and immune stressors in their environments.

Postcranial skeleton of Goodwin's brush-tailed mouse (Calomyscus elburzensis Goodwin, 1939) (Rodentia: Calomyscidae): Shape, size, function, and locomotor adaptation.

Goodwin's brush-tailed mouse (Calomyscus elburzensis Goodwin, 1939) is a poorly known small rodent that occupies rocky habitats in Iran, Turkmenistan, Afghanistan, Pakistan, Azerbaijan, and Syria. Herein, a detailed description of the shape, size, and function of the postcranial skeleton of this species is presented for the first time. Trapping was carried out in eastern Iran between the years 2013 and 2015. Skeletal parts of 24 adult male specimens were removed using the papain digestion protocol, and several postcranial morphological characteristics and measurements were examined. We attempted to achieve a morpho-functional characterization of Goodwin's brush-tailed mouse and to match morphological specializations with previous information on the ecology, behavior, and phylogenetic inferences of this rodent. Goodwin's brush-tailed mouse has extended transverse processes and long zygapophyses in the first five caudal vertebrae along with a good innervation of the caudal vertebrae, which has resulted in a well-developed basal musculature of the tail. It has extended forelimb, long ilium, and short post-acetabular part of the innominate bone, loose hip joint with high degree of lateral movement of the hindlimb, and long distal elements of the hindlimb. These features have resulted in fast terrestrial movements in open microhabitats, including climbing and jumping. Although superficial scratching of the ground is observed, the species is incapable of digging burrows. Evaluation of postcranial morphological characteristics and character states further indicated the basal radiation of the genus Calomyscus among other Muroidea. Findings constitute a source of information for morpho-functional and phylogenetic comparisons between Calomyscidae and other mouse-like muroids.

Reproductive and immune effects emerge at similar thresholds of PFHxS in deer mice.

Although perfluorohexane sulfonate (PFHxS) is structurally similar to perfluorooctane sulfonate (PFOS) and also widely detected in humans and the environment, comparatively fewer toxicity data exists on this 6-chain perfluoroalkyl sulfonic acid. In this study, repeated oral doses of PFHxS were administered to deer mice (Peromyscus maniculatus) to evaluate subchronic toxicity and potential effects on reproduction and development. Maternal oral exposure to PFHxS caused increased stillbirths, which is relevant for ecological risk assessment, and resulted in a benchmark dose lower limit (BMDL) of 5.72 mg/kg-d PFHxS. Decreased plaque formation, which is relevant for human health risk assessment, occurred in both sexes of adult animals (BMDL = 8.79 mg/kg-d PFHxS). These data are the first to suggest a direct link between PFHxS and decreased functional immunity in an animal model. Additionally, female animals exhibited increased liver:body weight and animals of both sexes exhibited decreased serum thyroxine (T4) levels. Notably, since reproductive effects were used to support 2016 draft health advisories and immune effects were used in 2022 drinking water health advisories released by the United States Environmental Protection Agency for PFOS and perfluorooctanoic acid (PFOA), these novel data can potentially support advisories for PFHxS because relevant points of departure emerge at similar thresholds in a wild mammal and corroborate the general understanding of per- and polyfluoroalkyl substances (PFAS).

Ecological interactions driving population dynamics of two tick-borne pathogens, Borrelia burgdorferi and Babesia microti.

Borrelia burgdorferi (Bb) and Babesia microti (Bm) are vector-borne zoonotic pathogens commonly found co-circulating in Ixodes scapularis and Peromyscus leucopus populations. The restricted distribution and lower prevalence of Bm has been historically attributed to lower host-to-tick transmission efficiency and limited host ranges. We hypothesized that prevalence patterns are driven by coinfection dynamics and vertical transmission. We use a multi-year, multiple location, longitudinal dataset with mathematical modelling to elucidate coinfection dynamics between Bb and Bm in natural populations of P. leucopus, the most competent reservoir host for both pathogens in the eastern USA. Our analyses indicate that, in the absence of vertical transmission, Bb is viable at lower tick numbers than Bm. However, with vertical transmission, Bm is viable at lower tick numbers than Bb. Vertical transmission has a particularly strong effect on Bm prevalence early in the active season while coinfection has an increasing role during the nymphal peak. Our analyses indicate that coinfection processes, such as facilitation of Bm infection by Bb, have relatively little influence on the persistence of either parasite. We suggest future work examines the sensitivity of Bm vertical transmission and other key processes to local environmental conditions to inform surveillance and control of tick-borne pathogens.

Adaptive structural and functional evolution of the placenta protects fetal growth in high-elevation deer mice.

Environmental hypoxia challenges female reproductive physiology in placental mammals, increasing rates of gestational complications. Adaptation to high elevation has limited many of these effects in humans and other mammals, offering potential insight into the developmental processes that lead to and protect against hypoxia-related gestational complications. However, our understanding of these adaptations has been hampered by a lack of experimental work linking the functional, regulatory, and genetic underpinnings of gestational development in locally adapted populations. Here, we dissect high-elevation adaptation in the reproductive physiology of deer mice (Peromyscus maniculatus), a rodent species with an exceptionally broad elevational distribution that has emerged as a model for hypoxia adaptation. Using experimental acclimations, we show that lowland mice experience pronounced fetal growth restriction when challenged with gestational hypoxia, while highland mice maintain normal growth by expanding the compartment of the placenta that facilitates nutrient and gas exchange between gestational parent and fetus. We then use compartment-specific transcriptome analyses to show that adaptive structural remodeling of the placenta is coincident with widespread changes in gene expression within this same compartment. Genes associated with fetal growth in deer mice significantly overlap with genes involved in human placental development, pointing to conserved or convergent pathways underlying these processes. Finally, we overlay our results with genetic data from natural populations to identify candidate genes and genomic features that contribute to these placental adaptations. Collectively, these experiments advance our understanding of adaptation to hypoxic environments by revealing physiological and genetic mechanisms that shape fetal growth trajectories under maternal hypoxia.