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Conserved Noncoding Cis-Elements Associated with Hibernation Modulate Metabolic and Behavioral Adaptations in Mice.

Susan Steinwand1, Cornelia Stacher Hörndli1, Elliott Ferris1

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Convergent evolution in hibernators reveals key cis-elements regulating metabolism. These genetic elements influence Fat Mass & Obesity (Fto) gene expression, impacting metabolic control and behavior.

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Area of Science:

  • Genomics
  • Evolutionary Biology
  • Metabolic Research

Background:

  • Mammalian hibernation involves complex physiological adaptations.
  • Conserved cis-elements play crucial roles in gene regulation and evolution.
  • The Fat Mass & Obesity (Fto) locus is implicated in metabolic regulation.

Purpose of the Study:

  • To elucidate the functional roles of conserved cis-elements in mammalian hibernation evolution.
  • To investigate the impact of cis-elements on gene expression and metabolic control.
  • To understand the behavioral and obesogenic effects of specific cis-elements.

Main Methods:

  • Genomic analyses to identify topologically associated domains (TADs) with convergent changes in hibernators.
  • Gene knockout studies in mice to assess cis-element function.
  • Phenotypic profiling across hibernation states and dietary challenges.

Main Results:

  • Identified TADs, including the Fto locus, with significant convergent genomic changes in hibernators.
  • Demonstrated that hibernation-linked cis-elements regulate Fto, Irx3, and Irx5 gene expression, affecting downstream genes.
  • Discovered distinct roles for cis-elements in metabolic control during different hibernation phases and varying diets.
  • Showcased one cis-element's influence on lean phenotype and foraging behavior.

Conclusions:

  • Convergent evolution in hibernators highlights functional genetic mechanisms of mammalian metabolic control.
  • Specific cis-elements are critical for regulating metabolism, obesity, and behavior.
  • These findings provide insights into the genetic basis of hibernation and metabolic adaptation.