Sorex araneus

Almost all mammals rely on the thymus and bone marrow to generate and differentiate B- and T cells essential for adaptive immunity. A few members of the family Soricidae, or true shrews, have also evolved the pancreas of Aselli, a kidney-sized organ hypothesized to serve this primary immune role, and whose gene expression profile is unknown. Here we introduce transcriptomes of juvenile Sorex araneus pancreas of Aselli, compare them to those of the spleen and chick bursa of Fabricius, an analogous and bird-specific organ, and explore differential expression overlaps with positively selected genes. While differential gene expression analyses revealed overexpression of genes that regulate the differentiation of B cells into long-term plasma cells (e.g., IRF4, XBP1, PRDM1) compared to the spleen and more convergent expression with the bursa of Fabricius than expected by chance (including IRF4), overlaps with positive selection were as expected and included PTPRCAP, which regulates both T and B cell antigen responses and lymph node size. Our results support the specialized role of the pancreas of Aselli in adaptive immunity, and we propose this unique organ evolved at the intersection between extreme metabolic demands and high parasite burdens in tiny yet very active shrews.

Sorex araneus, the Eurasian common shrew, has seasonal brain size plasticity (Dehnel’s phenomenon) and abundant intraspecific chromosomal rearrangements, but genomic contributions to these traits remain unknown. We couple a chromosome-scale genome assembly with seasonal brain transcriptomes to discover relationships between molecular changes and both traits. Positively selected genes enriched the Fanconi anemia DNA repair pathway, which prevents the accumulation of chromosomal aberrations, and is likely involved in chromosomal rearrangements (FANCI, FAAP100). Genes involved in neurogenesis show either signatures of positive selection (PCDHA6), seasonal differential expression in the cortex and hippocampus (Notch signaling), or both (SOX9), suggesting a role for cellular proliferation in seasonal brain shrinkage and regrowth. Both positive selection and evolutionary upregulation in the shrew hypothalamus of VEGFA and SPHK2 indicate adaptations in hypothalamic metabolic homeostasis have evolved together with Dehnel’s phenomenon. These findings reveal genomic changes central to the evolution of both chromosomal instability and cyclical patterns in brain gene expression that characterizes mammalian brain size plasticity.

To meet the challenge of wintering in place many high-latitude small mammals reduce energy demands through hibernation. In contrast, short-lived Eurasian common shrews, Sorex araneus, remain active and shrink, including energy-intensive organs in winter, regrowing in spring in an evolved strategy called Dehnel’s phenomenon. How this size change is linked to metabolic and regulatory changes to sustain their high metabolism is unknown. We analyzed metabolic, proteomic, and gene expression profiles spanning the entirety of Dehnel’s seasonal cycle in wild shrews. We show regulatory changes to oxidative phosphorylation and increased fatty acid metabolism during autumn-to-winter shrinkage, as previously found in hibernating species. But in shrews we also found upregulated winter expression of genes involved in gluconeogenesis: the biosynthesis of glucose from non-carbohydrate substrates. Co-expression models revealed changes in size and metabolic gene expression interconnect via FOXO signaling, whose overexpression reduces size and extends lifespan in many model organisms. We propose that while shifts in gluconeogenesis meet the challenge posed by high metabolic rate and active winter lifestyle, FOXO signaling is central to Dehnel’s phenomenon, with spring downregulation limiting lifespan in these shrews.

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 gene expression in the shrew hypothalamus, a brain region that both regulates metabolic homeostasis and drastically changes size, and compared hypothalamus gene 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. With high metabolic rates and facing harsh winter conditions, S. araneus have evolved both adaptive and plastic mechanisms to sense and regulate their energy budget. Many of these changes mirrored those identified in human neurological and metabolic disease, highlighting the interactions between metabolic homeostasis, brain size plasticity, and longevity.

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 …