DOI: 10.5061/dryad.sn02v6xgw
title: Genes underlying adaptive physiological shifts among hibernating mammals

description: Hibernation has evolved independently in several mammalian lineages,
 allowing animals to survive extreme environmental conditions through
 profound physiological shifts, including reduced metabolic rate, heart
 rate, respiration, and body temperature. These physiological shifts allow
 hibernators to rely solely on fat reserves, simultaneously avoiding the
 adverse effects of prolonged immobility seen in non-hibernating species.
 Although research on individual species has highlighted key aspects of
 these adaptations, the genetic basis of hibernation across mammals remains
 poorly understood. Synthesizing both single species and comparative
 approaches, we use metabolomic data from waking and hibernating black
 bears (Ursus americanus) to guide bioinformatic analyses of genes using
 tests of selection and evolutionary rate convergence across independent
 lineages of hibernating mammals. Our analyses reveal significant changes
 in carnitine levels between states. Using public databases we generate
 candidate genes which may contribute to regulation of carnitine, and use
 these to test for signatures of selection across several independent
 lineages of hibernating mammals. We also utilize a dataset of 19k proteins
 across 120 mammalian genomes to identify genes evolving at convergent
 rates across hibernating mammals.  Using both approaches, we find
 several novel genes likely to impact carnitine metabolism and related
 functions vital to hibernation such as metabolic shifts, oxidative stress,
 and tissue preservation. These findings provide new insights into the
 genetic basis of hibernation and offer promising targets for translational
 research, including the development of clinical therapies that mimic
 hibernation-like states for applications in medicine and space
 exploration.
description: # Genes underlying adaptive physiological shifts among hibernating mammals
 Dataset DOI: [10.5061/dryad.sn02v6xgw](10.5061/dryad.sn02v6xgw) This
 dataset accompanies the manuscript *"Genes Underlying Adaptive
 Physiological Shifts Among Hibernating Mammals"* and provides files
 used in comparative genomics and gene enrichment analyses related to
 hibernation and carnitine metabolism in mammals. ## File Descriptions **1.
 RERConverge_120MasterTree.tre** * Format: Newick (.tre) * Description:
 Species tree topology used in RERconverge analyses of gene-wide
 evolutionary rate shifts. **2. 206Species_MasterTree.tre** * Format:
 Newick (.tre) * Description: Full species tree for all species represented
 in the 404 carnitine-related genes from NCBI ortholog datasets. Used to
 prune gene-specific trees for selection tests. **3.
 19610_mammalGeneTrees.txt** * Format: Plain text (multi-line Newick
 format) * Description: Protein-based gene trees from 19,610 orthologs
 across 120 mammalian genomes, formatted for use in RERconverge. **4.
 19610_mammalGeneTrees.trees** * Format: Serialized .trees file (compatible
 with RERconverge) * Description: Same gene trees as above, but serialized
 for rapid use in RERconverge pipelines. --- ## RawEnrichmentData.xlsx –
 Sheet-by-Sheet Explanation This Excel file contains results from
 enrichment analyses testing functional enrichment in gene sets related to
 hibernation-associated selection signals. **➤ Summary_Unique_Enrichment**
 * **Purpose**: Summarizes unique gene ontology enrichments **only**
 observed in genes under selection (positive or relaxed) but **not** in the
 full 371-gene carnitine dataset. * **Highlights**: Significant after
 Bonferoni Correction * **Red Text**: Uniquely enriched in the focal group
 but not the background group test (ex: genes under positive selection vs
 all human genes, but not all 371 carnitine related genes vs all human
 genes) * **Columns**: * Category: GO or UniProt category (e.g.,
 GOTERM_MF_DIRECT) * Term: Enrichment term and ID * Count: Number of genes
 enriched * %: Percentage of genes in the list showing enrichment * PValue,
 Bonferroni, Benjamini, FDR: Statistical metrics * Genes: List of enriched
 genes * Fold Enrichment: Fold overrepresentation relative to background *
 List Total, Pop Hits, Pop Total: Gene counts in list vs. background **➤
 ALL_371_GenesVS_ALL_Human** * **Purpose**: GO and pathway enrichment for
 all 371 carnitine-related genes compared to the full human genome. *
 **Columns**: Same as above. Includes terms from KEGG, GO (CC, BP, MF), and
 UniProt keywords. **➤ PosSelGenesVS_ALL_Human** * **Purpose**: Enrichment
 results from genes identified as under **positive selection**. *
 **Interpretation**: Functional categories enriched among these positively
 selected genes. **➤ RelaxedSelGenesVS_ALL_Human** * **Purpose**:
 Enrichment results from genes under **relaxed selection**. *
 **Interpretation**: Functional categories losing constraint in hibernating
 lineages. **➤ 33_RERGenes_VS_19610_background** * **Purpose**: Enrichment
 test of the **33 RERconverge-significant genes** against all 19,610 genes
 from the main mammalian background set. --- ## Software and Code
 Requirements * **R** (v4.x) — Used for RERconverge analysis * **Excel** —
 For viewing the enrichment data * **Any text viewer** — To inspect .tre or
 .txt files ## Access information Data was derived from the following
 sources: * NCBI ortholog database  *
 [https://doi.org/10.1093/gigascience/giz159](https://doi.org/10.1093/gigascience/giz159) 120 mammalian genomes.