transcriptomics

Contrasting almost all other mammalian wintering strategies, Eurasian common shrews, Sorex araneus, endure winter by shrinking their brain, skull, and most organs, only to then regrow to breeding size the following spring. How such tiny mammals achieve this unique brain size plasticity while maintaining activity through the winter remains unknown. To discover potential adaptations underlying this trait, we analyzed seasonal differential expression in the shrew hypothalamus, a brain region that both regulates metabolic homeostasis and drastically changes size and compared hypothalamus expression across species. We discovered seasonal variation in suites of genes involved in energy homeostasis and apoptosis, shrew-specific upregulation of genes involved in the development of the hypothalamic blood brain barrier and calcium signaling, as well as overlapping seasonal and comparative gene expression divergence in genes implicated in the development and progression of human neurological and metabolic disorders, including CCDC22, FAM57B, and GPR3. With high metabolic rates and facing harsh winter conditions, Sorex araneus have evolved both adaptive and plastic mechanisms to sense and regulate its energy budget. Many of these expression changes mirrored those identified in human neurological and metabolic disease, highlighting the interactions between metabolic homeostasis, brain size plasticity, and longevity.

First isolated from neotropical fruit bats in Trinidad in 1956, Tacaribe virus (TCRV) has rarely been detected since. We searched for New World arenavirus reads in roughly 5.7 million sequencing runs available on public databases using Serratus. We recovered a complete genome of a divergent TCRV in metatranscriptomic data derived from heart and eye tissue of an adult male Jamaican fruit-eating bat sampled in the Dominican Republic, 2014. In total, 2,733 reads were mapped resulting in mean coverages of 7.4-fold for the L and 10.2-fold for the S segment. Re-testing original bat specimens showed the highest viral loads in liver tissue (245 copies/mg). Sanger sequencing of PCR amplicons from liver confirmed correctness of and completed the genome recovered from metatranscriptomic data, revealing conserved arenavirus genomic organization, length, intergenic regions, and genome termini. The newly found TCRV strain tentatively named DOM2014 clustered in a basal sister relationship to all other known TCRV strains with which it shared between 83.3%–86.0% genomic and 91.8%–93.7% translated amino acid sequence identity across protein-coding regions. DOM2014 showed a conserved glycine, proline, proline, threonine (GPPT) nucleopro­ tein motif, which is essential for TCRV interferon β antagonism. Our data confirm the association of TCRV with the bat genus Artibeus put into question by lethal experi­ mental infections and scarce bat-derived TCRV genomic data. Broad genetic diversity and geographic spread require assessments of TCRV strain-associated pathogenicity, particularly for DOM2014 as a highly divergent TCRV strain. Confirmation of genomic database findings by testing original specimens provides robustness to our findings and supports the usefulness of metatranscriptomic studies.

Compared to their free-ranging counterparts, wild animals in captivity are subject to different conditions with lasting effects on their physiology and behavior. Alterations in gene expression in response to environmental changes occur upstream of physiological and behavioral phenotypes, but there are no experiments analyzing differential gene expression in captive vs. free-ranging mammals. We assessed gene expression profiles of three brain regions (cortex, olfactory bulb, and hippocampus) of wild juvenile shrews (Sorex araneus) in comparison to shrews kept in captivity for two months. We found hundreds of differentially expressed genes in all three brain regions, suggesting a large and uniform captivity effect. Many of the downregulated genes in captive shrews significantly enrich pathways associated with neurodegenerative disease (p<0.001), oxidative phosphorylation (p<0.001), and genes encoding ribosomal proteins (p<0.001). Transcriptomic changes associated with captivity in the shrew resemble responses identified in several human pathologies, such as major depressive disorder and neurodegeneration. Thus, not only does captivity impact brain function and expression, but captivity effects may also confound analyses of natural physiological processes in wild individuals under captive conditions.

Human brains typically grow through development, then remain the same size in adulthood, and often shrink through age-related degeneration that induces cognitive decline and impaired functionality. In most cases, however, the neural and organismal changes that accompany shrinkage, especially early in the process, remain unknown. Paralleling neurodegenerative phenotypes, the Eurasian common shrew Sorex araneus, shrinks its brain in autumn through winter, but then reverses this process by rapidly regrowing the brain come spring. To identify the molecular underpinnings and parallels to human neurodegeneration of this unique brain size change, we analyzed multi-organ, season-specific transcriptomics and metabolomic data. Simultaneous with brain shrinkage, we discovered system-wide metabolic shifts from lipid to glucose metabolism, as well as neuroprotection of brain metabolic homeostasis through reduced cholesterol efflux. These mechanisms rely on a finely tuned brain-liver crosstalk that results in changes in expression of human markers of aging and neurodegeneration in Parkinson’s disease and Huntington’s disease. We propose metabolic shifts with signals that cross the brain blood barrier are central to seasonal brain size changes in S. araneus, with potential implications for therapeutic treatment of human neurodegeneration.

High viral tolerance coupled with an extraordinary regulation of the immune response makes bats a great model to study host-pathogen evolution. Although many immune-related gene gains and losses have been previously reported in bats, important gene families such as antimicrobial peptides (AMPs) remain understudied. We built an exhaustive bioinformatic pipeline targeting the major gene families of defensins and cathelicidins to explore AMP diversity and analyze their evolution and distribution across six bat families. A combination of manual and automated procedures identified 29 AMP families across queried species, with α-, β-defensins, and cathelicidins representing around 10% of AMP diversity. Gene duplications were inferred in both α-defensins, which were absent in five species, and three β-defensin gene subfamilies, but cathelicidins did not show significant shifts in gene family size and were absent in Anoura caudifer and the pteropodids. Based on lineage-specific gains and losses, we propose diet and diet-related microbiome evolution may determine the evolution of α- and β-defensins gene families and subfamilies. These results highlight the importance of building species-specific libraries for genome annotation in non-model organisms and shed light on possible drivers responsible for the rapid evolution of AMPs. By focusing on these understudied defenses, we provide a robust framework for explaining bat responses to pathogens.

Winters are challenging environmental periods, consisting of decreased temperature and nutrient limitations. The Eurasian common shrew, …

The common shrew, Sorex araneus, is a small mammal of growing interest in neuroscience research, as it exhibits dramatic and reversible …

In nature, encounters between humans and wildlife correlate with greater viral burdens in wildlife and therefore with higher risk of new viral pathogens spilling over into human populations. Yet, the factors contributing to this risk remain poorly understood, especially among highly mobile, but tightly packed populations of animals, such as cave-dwelling bats. Using the Egyptian fruitbat as a study system, this project seeks to understand how factors such as access to food, overall animal health, and responses to immune challenges influence each other in the wild to control the degree of viral infection in populations experiencing variable exposure to humans. The project will use highly integrative approaches to illuminate the fundamental biology of disease risk and to enhance the capacity to predict risks of viral spillover from bats to other wildlife or to humans. The project will also have broader impact on education and training by implementing an innovative active-learning experience, called “From the Bat Cave – Integrative Disease Research for Undergraduates”, in which postdoctoral researchers will learn to apply integrative research and mentoring methods to involve cohorts of undergraduate students in research and peer-peer mentoring through GBatNet, a NSF-funded international network of bat research groups.

While evolvability of genes and traits may promote specialization during species diversification, how ecology subsequently restricts such variation remains unclear. Chemosensation requires animals to decipher a complex chemical background to locate fitness-related resources, and thus the underlying genomic architecture and morphology must cope with constant exposure to a changing odorant landscape; detecting adaptation amidst extensive chemosensory diversity is an open challenge. In phyllostomid bats, an ecologically diverse clade that evolved plant-visiting from an insectivorous ancestor, the evolution of novel food detection mechanisms is suggested to be a key innovation, as plant-visiting species rely strongly on olfaction, supplementarily using echolocation. If this is true, exceptional variation in underlying olfactory genes and phenotypes may have preceded dietary diversification. We compared olfactory receptor (OR) genes sequenced from olfactory epithelium transcriptomes and olfactory epithelium surface area of bats with differing diets. Surprisingly, although OR evolution rates were quite variable and generally high, they are largely independent of diet. Olfactory epithelial surface area, however, is relatively larger in plant-visiting bats and there is an inverse relationship between OR evolution rates and surface area. Relatively larger surface areas suggest greater reliance on olfactory detection and stronger constraint on maintaining an already diverse OR repertoire. Instead of the typical case in which specialization and elaboration are coupled with rapid diversification of associated genes, here the relevant genes are already evolving so quickly that increased reliance on smell has led to stabilizing selection, presumably to maintain the ability to consistently discriminate among specific odorants — a potential ecological constraint on sensory evolution.

In most vertebrates, the demand for glucose as the primary substrate for cellular respiration is met by the breakdown of complex …