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The tree squirrel HP-25 gene is a pseudogene.

M Kojima1, T Shiba, N Kondo

  • 1Department of Biosciences, School of Science, Kitasato University, Kanagawa Japan.

European Journal of Biochemistry
|November 28, 2001
PubMed
Summary

The hibernation-specific HP-25 gene is not expressed in tree squirrels due to a mutation. This genetic difference, specifically in the HNF-4 binding site, prevents gene activation in non-hibernating species.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Comparative Genomics

Background:

  • The HP-25 protein is crucial for hibernation and is expressed in hibernating squirrels but not in non-hibernating species.
  • Understanding the genetic basis of hibernation provides insights into physiological adaptations.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying the lack of HP-25 gene expression in tree squirrels.
  • To compare the gene structure and promoter activity of the HP-25 gene between hibernating chipmunks and non-hibernating tree squirrels.

Main Methods:

  • Gene isolation and structural comparison between tree squirrel and chipmunk HP-25 genes.
  • Analysis of promoter activity using HepG2 cells and identification of transcription factor binding sites.
  • Site-directed mutagenesis to assess the impact of specific mutations on HNF-4 binding and gene transactivation.

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Main Results:

  • Tree squirrel HP-25 gene has conserved exon structure but contains a 13-nucleotide insertional mutation in exon 2, disrupting the open reading frame (ORF).
  • The 5' flanking sequence of the chipmunk HP-25 gene exhibits liver-specific promoter activity, dependent on HNF-4 binding.
  • The corresponding region in the tree squirrel HP-25 gene shows minimal promoter activity, with impaired HNF-4 binding, likely due to a point mutation in the HNF-4 binding site.

Conclusions:

  • An insertional mutation in exon 2 disrupts the HP-25 coding sequence in tree squirrels.
  • A critical point mutation within the HNF-4 binding site of the promoter region is responsible for the absence of HP-25 gene expression in tree squirrels.
  • This mutation highlights the role of specific genetic alterations in the evolution of hibernation phenotypes.