Biology subjects

Sheehan, M. J.

Publications and source records attributed to Sheehan, M. J..

At least 19 recordsLinked to original sources

bioRxiv2025

The Sikkim mouse (Mus pahari) exhibits distinct spatial, circadian, and social behaviors compared to laboratory mice

While the laboratory mouse is one of the most studied organisms on the planet, comparative research on the spatial and social structures of closely related Mus species remains limited. Here, we characterize the spatial, circadian, and social behavior of the Sikkim mouse (Mus pahari) wild-derived inbred strain PAH/Eij in comparison to the laboratory mouse strain C57BL/6J (Mus musculus domesticus, shortened to B6). Using a common garden approach, we monitored mice in replicate mixed-sex group social behavior trials within an indoor mesocosm using radiofrequency identification (RFID) antennae. M. pahari exhibited markedly reduced spatial exploration and highly stereotyped circadian activity that was strongly coupled to the dark phase of the light-dark cycle compared to B6 mice. Most strikingly, M. pahari displayed distinctive social behaviors characterized by strong male-male gregariousness and enhanced overall social tolerance, contrasting sharply with the relatively less social nature of B6 mice. These results demonstrate the genetic influence on social organization within the Mus genus and identify unique socio-spatial phenotypes in M. pahari, highlighting the considerable potential of this strain and species as a novel model for social behavior research.

animal behavior and cognition↗

bioRxiv2025

The mouse gut microbiota responds to predator odor and predicts host behavior

Chronic stressors can alter the mammalian gut microbiota in ways that mediate host stress responses, but the impacts of acute stressors on these interactions are less well understood. Here, we show that brief exposure of wild-derived mice to predator odor altered gut-microbiota composition, which in turn predicted host behavior. We investigated the individual and combined effects of 15-minute exposures to synthetic fox fecal odor and 30 days of chronic social isolation, an established chronic stressor. Using ethological assays, visceral adipose tissue transcriptomics, and genome-resolved metagenomics, we found that predator-odor exposure significantly affected mouse behavior, gene expression, and gut microbiota. Predator odor-responsive bacteria were associated with the expression of genes involved in anti-microbial defense, and host behavioral responses were predicted by random forest models trained on gut-microbiota profiles. These findings indicate interactions between the gut microbiota and wild-mouse responses to the threat of predation, an ecologically relevant acute stressor.

microbiology↗

bioRxiv2025

DeltaBreed: A BrAPI-centric breeding data information system

DeltaBreed is a unified breeding data management system designed by Breeding Insight (BI, Cornell University) to serve the wide diversity of USDA-ARS specialty crop and animal breeding programs. DeltaBreed has a RESTful microservice architecture that utilizes the BrAPI Java Test Server as its primary database. The system is interoperable with many BrAPI-compliant applications (BrApps), including Field Book, and is continually aligned with the most recent BrAPI specifications. Here, we describe the features of DeltaBreed and provide several interoperability test cases to illustrate successes and challenges encountered during development. We also discuss future expansion and enhancement plans for DeltaBreed, as well as outline possible solutions to known limitations.

bioinformatics↗

bioRxiv2024

Rewilding alters mouse epigenetic aging

The aging of mammalian epigenomes fundamentally alters cellular functions, and such changes are the focus of many healthspan and lifespan studies. However, studies of this process typically use mouse models living under standardized laboratory conditions and neglect the impact of variation in social, physical, microbial, and other aspects of the living environment on age-related changes. We examined differences in age-associated methylation changes between traditionally lab-reared and "rewilded" C57BL6/J mice, which lived in an outdoor field environment with enhanced ecological realism. Systematic analysis of age-associated methylation dynamics in the liver indicates a genomic region-conditioned, faster epigenetic aging rate in mice living in the field than those living in the lab, implicating perturbed 3D genome conformation and liver function. Altered epigenetic aging rates were more pronounced in sites that gain methylation with age, including sites enriched for transcription factor binding related to DNA repair. These observations underscore the overlooked role of the social and physical environment in epigenetic aging with implications for both basic and applied aging research.

genomics↗

bioRxiv2024

Seasonality of the estrus cycle in laboratory mice under constant conditions

Seasonality governs every aspect of life in the natural environment. Controlled laboratory settings are intended to keep animals under a constant set of environmental cues with no seasonality. However, prior research suggests that seasonal variation may exist despite aseasonal lab environments. Here, we examined if seasonal reproductive variation was present in a laboratory mouse strain (C57BL/6J) under standard laboratory housing conditions. We found that female C57BL/6J mice exhibited reproductive seasonality mirroring the outside environment, in a controlled "simulated summer" environment. In the winter and spring, females have longer ovulating phases (proestrus and estrus), compared to the fall. Females similarly experience lengthier complete cycles in the spring, with the most rapid cycling occurring in the fall. Additionally, females spent more time in ovulating phases across seasons than previously reported. Laboratory mice are sensitive to external seasonal changes, despite their local environment being light, temperature, and humidity controlled. This may be due to the detection of an unidentified external cue providing information about external seasonal changes. These findings represent just one example of how seasonality may impact mouse physiology in laboratory settings, emphasizing the need to account for such influences in biomedical research.

physiology↗

bioRxiv2024

Lineage-specific patterns of sexually dimorphic antennal transcription in the paper wasp Polistes fuscatus

Olfaction mediates many behaviors in social Hymenoptera, with sexual dimorphism in antennal transcription associated with different behaviors between sexes. Females display coordinated social behaviors within colonies, while males exhibit limited social behavior but are selected for finding mates. The expanded "9-exon" odorant receptor (OR) gene subfamily is associated with chemical communication and exhibits strongly female biased antennal transcription in ants and honey bees. Polistine wasps represent an independent evolution of sociality and associated expansion of 9-exon ORs, though antennal expression patterns are unknown. Here, we report distinct patterns of sexually dimorphic OR transcription in Polistes fuscatus compared to ants and bees. Most P. fuscatus 9-exon transcripts were detected at similar levels in males and females, and some were male biased. We also report differential antennal transcription of cytochromes P450 and muscle-related genes between sexes. We discuss these patterns in the context of the unique sexual and social behaviors of Polistes wasps, including prolonged male mating aggregations and male antennal tapping and curling during courtship and copulation. These results call attention to the lineage-specific selective pressures shaping sexually dimorphic antennal transcription in social insects.

evolutionary biology↗

bioRxiv2024

Multi-trait modeling and machine learning discover new markers associated with stem traits in alfalfa

Alfalfa biomass can be fractionated into leaf and stem components. Leaves comprise a protein-rich and highly digestible portion of biomass for ruminant animals, while stems constitute a high fiber and less digestible fraction, representing 50 to 70% of the biomass. However, little attention has focused on stem-related traits, which are a key aspect in improving the nutritional value and intake potential of alfalfa. This study aimed to identify molecular markers associated with four morphological traits in a panel of five populations of alfalfa generated over two cycles of divergent selection based on 16-h and 96-h in vitro neutral detergent fiber digestibility in stems. Phenotypic traits of stem color, presence of stem pith cells, winter standability, and winter injury were modeled using univariate and multivariate spatial mixed linear models (MLM), and the predicted values were used as response variables in genome-wide association studies (GWAS). The alfalfa panel was genotyped using a 3K DArTag SNP markers for the evaluation of the genetic structure and GWAS. Principal component and population structure analyses revealed differentiations between populations selected for high- and low-digestibility. Thirteen molecular markers were significantly associated with stem traits using either univariate or multivariate MLM. Additionally, support vector machine (SVM) and random forest (RF) algorithms were implemented to determine marker importance scores for stem traits and validate the GWAS results. The top-ranked markers from SVM and RF aligned with GWAS findings for solid stem pith, winter standability, and winter injury. Additionally, SVM identified additional markers with high variable importance for solid stem pith and winter injury. Most molecular markers were located in coding regions. These markers can facilitate marker-assisted selection to expedite breeding programs to increase winter hardiness or stem palatability. Author SummaryThe alfalfa stem constitutes a significant portion of forage yield, accounting for 50 to 70% of biomass yield, and influences various traits including plant height, standability, and digestibility. In our study, we identified thirteen molecular markers associated with stem color, presence of stem pith parenchyma, winter standability, and winter injury in a panel of five divergent stem digestibility populations. Multivariate trait modeling enhances the correlation among traits, thereby expanding the number of markers associated via GWAS. Similarly, machine learning algorithms increase the confidence of markers initially identified by GWAS and uncover new candidate regions that could serve as associated markers. Genes harboring markers associated to the four stem traits play roles in plant growth, response to plant injury, or tolerance to cold, underscoring their potential utility in enhancing traits such as cold tolerance and forage quality in alfalfa.

genomics↗

bioRxiv2024

Sex-specific competitive social feedback amplifies the role of early life contingency in male mice

Contingency (or luck) in early life plays an important role in shaping individuals development. When individuals live within larger societies, social experiences may cause the importance of early contingencies to be magnified or dampened. Here we test the hypothesis that competition magnifies the importance of early contingency in a sex-specific manner by comparing the developmental trajectories of genetically identical, free-living mice who either experienced high levels of territorial competition (males) or did not (females). We show that male territoriality results in a competitive feedback loop that magnifies the importance of early contingency and pushes individuals onto divergent, self-reinforcing life trajectories, while the same process appears absent in females. Our results indicate that the strength of sexual selection may be self-limiting, as within-sex competition increases the importance of early life contingency, thereby reducing the ability of selection to lead to evolution. They also demonstrate the potential for contingency to lead to dramatic differences in life outcomes, even in the absence of any underlying differences in ability ( merit).

evolutionary biology↗

bioRxiv2024

Neural correlates of individual facial recognition in a social wasp

Individual recognition is critical for social behavior across species. Whether recognition is mediated by circuits specialized for social information processing has been a matter of debate. Here we examine the neurobiological underpinning of individual visual facial recognition in Polistes fuscatus paper wasps. Front-facing images of conspecific wasps broadly increase activity across many brain regions relative to other stimuli. Notably, we identify a localized subpopulation of neurons in the protocerebrum which show specialized selectivity for front-facing wasp images, which we term wasp cells. These wasp cells encode information regarding the facial patterns, with ensemble activity correlating with facial identity. Wasp cells are strikingly analogous to face cells in primates, indicating that specialized circuits are likely an adaptive feature of neural architecture to support visual recognition. One-Sentence SummaryWe identify a localized population of neurons specifically tuned to wasp faces in a social wasp that has independently evolved individual facial recognition analogous to the face cells of primates.

neuroscience↗

bioRxiv2023

Adaptive genomic variation is linked to a climatic gradient in a social wasp

Species vary in their ability to adapt to rapid changes, with the presence of genetic variation often facilitating long-term evolutionary responses. Given the impending threat of climate change, it is critical to investigate how genetic variation facilitates persistence and possible range expansion in animals. Here, we combine genomic and climatic data to characterize the drivers of local adaptation in the widely distributed, social wasp Mischocyttarus mexicanus cubicola. Using whole genome sequence data, we show that adaptive genomic variation is linked to a climatic gradient across the broad distribution of this species. We found strong population structure, dividing the species into two genetic clusters that follow subtropical and temperate regions. Patterns of gene flow across the range deviate from those expected by isolation by distance alone with climatic differences resulting in reduced gene flow even between adjacent populations. Importantly, genotype-environment analyses reveal candidate single nucleotide polymorphism (SNPs) associated with temperature and rainfall, suggesting adaptation for thermal and desiccation tolerance. In particular, candidate SNPs in or near mitochondrial genes ND5, CO1, and COIII are linked to cold tolerance and metabolism. Similarly, the Gld nuclear gene shown to mediate cold hardiness and cuticle formation, shows two candidate SNPs with non-synonymous mutations unique to temperate populations. Together, our results reveal candidate SNPs consistent with local adaptation to distinct climatic conditions. Thus, the integration of genomic and climatic data can be a powerful approach to predict vulnerability and persistence of species under rapid climate change.

evolutionary biology↗

bioRxiv2023

Into the Wild: A novel wild-derived inbred strain resource expands the genomic and phenotypic diversity of laboratory mouse models

The laboratory mouse has served as the premier animal model system for both basic and preclinical investigations for a century. However, laboratory mice capture a narrow subset of the genetic variation found in wild mouse populations. This consideration inherently restricts the scope of potential discovery in laboratory models and narrows the pool of potentially identified phenotype-associated variants and pathways. Wild mouse populations are reservoirs of predicted functional and disease-associated alleles, but the sparsity of commercially available, well-characterized wild mouse strains limits their broader adoption in biomedical research. To overcome this barrier, we have recently imported, sequenced, and phenotyped a set of 11 wild-derived inbred strains developed from wild-caught Mus musculus domesticus. Each of these "Nachman strains" immortalizes a unique wild haplotype sampled from five environmentally diverse locations across North and South America: Saratoga Springs, New York, USA; Gainesville, Florida, USA; Manaus, Brazil; Tucson, Arizona, USA; and Edmonton, Alberta, Canada. Whole genome sequence analysis reveals that each strain carries between 4.73-6.54 million single nucleotide differences relative to the mouse reference assembly, with 42.5% of variants in the Nachman strain genomes absent from classical inbred mouse strains. We phenotyped the Nachman strains on a customized pipeline to assess the scope of disease-relevant neurobehavioral, biochemical, physiological, metabolic, and morphological trait variation. The Nachman strains exhibit significant inter-strain variation in >90% of 1119 surveyed traits and expand the range of phenotypic diversity captured in classical inbred strain panels alone. Taken together, our work introduces a novel wild-derived inbred mouse strain resource that will enable new discoveries in basic and preclinical research. These strains are currently available through The Jackson Laboratory Repository under laboratory code NachJ.

genetics↗

bioRxiv2023

Major urinary protein (Mup) gene family deletion drives sex-specific alterations on the house mouse gut microbiota

The gut microbiota is shaped by host metabolism. In house mice (Mus musculus), major urinary protein (MUP) pheromone production represents a considerable energy investment, particularly in sexually mature males. Deletion of the Mup gene family shifts mouse metabolism towards an anabolic state, marked by lipogenesis, lipid accumulation, and body mass increases. Given the metabolic implications of MUPs, they may also influence the gut microbiota. Here, we investigated the effect of deletion of the Mup gene family on the gut microbiota of sexually mature mice. Shotgun metagenomics revealed distinct taxonomic and functional profiles between wildtype and knockout males, but not females. Deletion of the Mup gene cluster significantly reduced diversity in microbial families and functions in male mice. Additionally, specific taxa of the Ruminococcaceae family, which is associated with gut health and reduced risk of developing metabolic syndrome, and several microbial functions, such as transporters involved in vitamin B5 acquisition, were significantly depleted in the microbiota of Mup-knockout males. Altogether these results show that major urinary proteins significantly affect the gut microbiota of house mouse in a sex-specific manner. ImportanceThe community of microorganisms that inhabit the gastrointestinal track of animals, known as the gut microbiota, can have profound effects on host phenotypes. The gut microbiota is in turn shaped by host genes, including those involved with host metabolism. In adult male house mice, expression of the major urinary protein (Mup) gene cluster represents a substantial energy investment, and deletion of Mup gene family leads to fat accumulation and weight gain in males. We show for the first time that deleting Mup genes also alters the gut microbiota of male, but not female, mice in terms of both taxonomic and functional composition. Male mice without Mup genes harbored fewer gut bacterial families and reduced abundances of several species, including bacteria previously shown to reduce obesity risk. Studying the impact of the Mup genes on the gut microbiota will help us understand how these genes influence host phenotype more broadly.

microbiology↗

bioRxiv2023

Genetically Identical Mice Express Alternative Reproductive Tactics Depending on Social Conditions in the Field

In many species, establishing and maintaining a territory is critical to survival and reproduction, and an animals ability to do so is strongly influenced by the presence and density of competitors. Here we manipulate social conditions to study the alternative reproductive tactics displayed by genetically identical, age-matched laboratory mice competing for territories under ecologically realistic social environmental conditions. We introduced adult males and females of the laboratory mouse strain (C57BL/6J) into a large, outdoor field enclosure containing defendable resource zones under one of two social conditions. We first created a low-density social environment, such that the number of available territories exceeded the number of males. After males established stable territories, we introduced a pulse of intruder males and observed the resulting defensive and invasive tactics employed. In response to this change in social environment, males with large territories invested more in patrolling but were less effective at excluding intruder males as compared to males with small territories. Intruding males failed to establish territories and displayed an alternative tactic featuring greater exploration as compared to genetically identical territorial males. Alternative tactics did not lead to equal reproductive success--males that acquired territories experienced greater survival and had greater access to females.

ecology↗

bioRxiv2022

Local adaptation of host-species specific gut microbiota

Mammalian species harbor compositionally distinct gut microbial communities, but the mechanisms that maintain specificity of symbionts to host species remain unclear. Here we show that natural selection within house mice (Mus musculus domesticus) drives deterministic assembly of the house-mouse gut microbiota from mixtures of native and non-native microbiotas. Competing microbiotas from wild-derived lines of house mice and other mouse species (Mus and Peromyscus spp.) within germ-free wildtype (WT) and Rag1-knockout (Rag1-/-) house mice revealed widespread fitness advantages for native gut bacteria. Certain native Bacteriodetes and Firmicutes favored by selection in WT hosts were not favored or disfavored in Rag1-/- hosts, which lack adaptive immunity, indicating that Rag1 mediates fitness advantages of these strains. This study demonstrates local adaptation of gut microbiota to a mammalian species. One-Sentence SummaryAdaptive advantages for native bacteria underlie the assembly of the mouse gut microbiota.

evolutionary biology↗

bioRxiv2022

Reproductive state switches the valence of male urinary pheromones in female mice

Internal states shape responses to sensory stimuli. Mammalian female reproductive states are understudied considering they are one of the most regular state changes in the animal kingdom. Here we examine female house mouse preferences toward male odors across the reproductive states of estrus and late-stage pregnancy. In house mice, urine scent marks are salient social odors that convey information about the sex and identity of individuals by major urinary proteins (MUPs). Males secrete a sex-specific pheromonal protein called darcin (MUP20). Additionally, genetically diverse mice secrete unique combinations of MUPs used in individual recognition. Prior work has revealed that male odors are powerful social stimuli for female mice, yet we have a limited understanding of how the valence of such odors change across reproductive states. We discovered a valence shift among estrus and pregnant females toward novel male urine, in which estrus females exhibit preference and pregnant females show strong avoidance. This valence switch also occurs toward darcin alone, providing further support for darcin as a strong sexual signal. However, when presented with familiar male urine, the approach-avoidance response disappears, even when additional darcin is added. In contrast, when an existing identity protein (MUP11) is added to familiar male urine the approach-avoidance response is recovered. This indicates that darcin in the absence of other identity information denotes a novel male and that familiar identity information present in male urine is sufficient to modify responses to darcin. Our findings suggest that the sex and identity information encoded by MUPs are likely processed via distinct, and potentially opposing pathways, that modulate responses toward complex social odor blends. Furthermore, we identify a state-modulated shift in decision-making toward social odors and propose a neural circuit model for this flow of information. These data underscore the importance of physiological state and signal context for interpreting the meaning and importance of social odors.

animal behavior and cognition↗

bioRxiv2022

Postural analysis reveals persistent vigilance in paper wasps after conspecific challenge

Vigilant animals detect and respond to threats in the environment, often changing posture and movement patterns. In social animals vigilance is modulated not only by predators but also by threatening conspecifics. Precisely how social interactions alter vigilance behavior over time is not well understood. We report persistent effects of a simulated social challenge on the vigilance behavior of wild northern paper wasp foundresses, Polistes fuscatus. During the founding phase of the colony cycle conspecific wasps may usurp nests from the resident foundress, representing a severe threat. Using postural tracking, we found that after simulated intrusions wasps displayed increased vigilance during the minutes after the threat was removed. Sustained vigilance elicited after social threat manifested as increased movement, greater bilateral wing extension, and reduced antennal separation. However, no postural changes were observed after a control stimulus presentation. By rapidly adjusting individual vigilance behavior after fending off a conspecific intruder, paper wasp foundresses invest in surveillance of potential social threats, even when such threats are no longer immediately present. The prolonged state of vigilance observed here is relevant to plasticity of recognition processes as a result of conspecific threats.

animal behavior and cognition↗

bioRxiv2022

Scent mark signal investment predicts fight dynamics in house mice

Signals mediate competitive interactions by allowing rival assessment, yet are often energetically expensive to produce. Individuals face tradeoffs when deciding when and where to signal, such that over or under-investing in signaling effort can be costly. One of the key mechanisms maintaining signal reliability is via social costs. While the social costs of over-signaling are well-known, the social costs of under-signaling are underexplored, particularly for dynamic signals. In this study we investigate a dynamic and olfactory-mediated signaling system that is ubiquitous among mammals: scent marking. Male house mice territorially scent mark their environment with metabolically costly urine marks. While competitive male mice are thought to deposit abundant scent marks in the environment, we recently identified a cohort of low-marking males that win fights. Whereas there are clear energetic costs to investing in urine signals in mice, we hypothesized that there may be social costs imposed on individuals who under-invest in signaling. Here we find that scent mark investment predicts fight dynamics. Despite fight outcome being unambiguous, aggressive intensity varies considerably across trials. Males that produce fewer scent marks engage in more intense fights that take longer to resolve. This effect appears to be driven by an unwillingness among losers to acquiesce to weakly signaling winners. We therefore find evidence for rival assessment of scent marks as well as social costs to under-signaling, which supports existing hypotheses for the importance of social punishment in maintaining optimal signaling equilibria. Our results further highlight the possibility of diverse signaling strategies in house mice.

ecology↗

bioRxiv2022

Dynamic changes to signal allocation rules in response to variable social environments in house mice

Male house mice use metabolically costly urine marks in intrasexual competition and mate attraction. Given the high costs of signaling and the depletable nature of urine reserves, males should dynamically modulate signal allocation as the social landscape is updated with new information. We investigate which aspects of male urine marking behavior are static or dynamic in light of changing social environments. To do this, we use thermal imaging to capture spatiotemporal data of urine deposition decisions. This novel method reveals fine-scale variation in urinary motor patterns in response to competition and social odors. Males demonstrate striking winner-loser effects in both the total allocation effort and temporal dynamics of scent marking. We find that competitive experience primes key temporal features of signal allocation and modulates responses to familiar and unfamiliar male scents. Males adjust their signaling effort, mark latency, and scent mark rhythm, depending on the scent identities present in the environment. Winners dramatically increase marking effort toward unfamiliar compared to familiar male scent, consistent with a dear enemy effect. Losers, in contrast, greatly reduce marking to unfamiliar scent but increase marking effort to the scent of their familiar rival, consistent with a nasty neighbor effect. Counter to the high lability of many features, the initial signal investment pattern influences allocation decisions days later, revealing the possibility of alternative scent mark strategies among competitive males. Thus, different features of urine mark signal allocation vary in responsiveness to fluctuating social landscapes, suggesting there are multiple distinct behavioral modules underlying marking behavior.

ecology↗