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Abstract Hibernation in brown bears is an annual process involving multiple physiologically distinct seasons—hibernation, active, and hyperphagia. While recent studies have characterized broad patterns of differential gene regulation and isoform usage between hibernation and active seasons, patterns of gene and isoform expression during hyperphagia remain relatively poorly understood. The hyperphagia stage occurs between active and hibernation seasons and involves the accumulation of large fat reserves in preparation for hibernation. Here, we use time-series analyses of gene expression and isoform usage to interrogate transcriptomic regulation associated with all three seasons. We identify a large number of genes with significant differential isoform usage (DIU) across seasons and show that these patterns of isoform usage are largely tissue-specific. We also show that DIU and differential gene-level expression responses are generally non-overlapping, with only a small subset of multi-isoform genes showing evidence of both gene-level expression changes and changes in isoform usage across seasons. Additionally, we investigate nuanced regulation of candidate genes involved in the insulin signaling pathway and find evidence of hyperphagia-specific gene expression and isoform regulation that may enhance fat accumulation during hyperphagia. Our findings highlight the value of using temporal analyses of both gene- and isoform-level gene expression when interrogating complex physiological phenotypes and provide new insight into the mechanisms underlying seasonal changes in bear physiology.
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This content will become publicly available on July 4, 2026
Genomic Insights into Bear Hibernation
Hibernation is a fascinating adaptation to food-scarce winters, characterized by significant physiological and behavioral changes, including fasting, inactivity, and insulin resistance. While hibernation is critical for the survival of many species, hibernation-related traits are often considered pathological in humans. Hibernation has been studied from a genomic perspective, especially with respect to transcription across multiple tissues. These studies have identified the differential activity of signaling pathways related to metabolism, tissue protection, and other mechanisms likely underlying hibernation phenotypes. Bears, in particular, are an interesting model for physiological and genomic studies of hibernation due to their large size and unique mode of hibernation compared to other small mammalian hibernators. Investigating the intricate molecular mechanisms underlying bear hibernation may therefore provide insight into fundamental biological processes with potential translational implications for human health, particularly with respect to metabolic disorders such as type II diabetes. This review focuses on recent advances and outstanding questions related to the exploration of bear hibernation from a genomic perspective.
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- Award ID(s):
- 2430336
- PAR ID:
- 10630434
- Publisher / Repository:
- Annual Reviews Inc.
- Date Published:
- Journal Name:
- Annual Review of Genetics
- ISSN:
- 0066-4197
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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