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Molecular evolution of proglucagon.

D M Irwin1

  • 1Department of Laboratory Medicine and Pathobiology, Banting and Best Diabetes Centre, Faculty of Medicine, University of Toronto, 100 College St., ON, M5G 1L5, Toronto, Canada. david.irwin@utoronto.ca

Regulatory Peptides
|February 17, 2001
PubMed
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The vertebrate proglucagon gene evolved slowly, with hormones like glucagon-like peptide-1 (GLP-1) and GLP-2 changing functions. Mammalian GLP-2 gained new functions, indicating evolutionary adaptation.

Area of Science:

  • Evolutionary biology
  • Molecular biology
  • Endocrinology

Background:

  • The vertebrate proglucagon gene produces glucagon, GLP-1, and GLP-2.
  • Understanding the evolution of these hormones' functions is crucial.

Purpose of the Study:

  • To investigate the evolutionary history and functional diversification of glucagon, GLP-1, and GLP-2.
  • To analyze the evolutionary rates and selective pressures on these hormones across vertebrates.

Main Methods:

  • Comparative analysis of proglucagon gene structure and sequences across vertebrate classes.
  • Examination of amino acid sequence evolution rates for glucagon, GLP-1, and GLP-2.
  • Tracing functional shifts, such as GLP-1's transition to an incretin in mammals.

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Main Results:

  • Proglucagon gene structure is conserved in vertebrates; duplications are rare, linked to genome duplication.
  • Hormone evolution is episodic, with varying selective constraints across vertebrate lineages.
  • Mammalian GLP-2 shows rapid evolution, suggesting a novel function distinct from other vertebrates.
  • Key functional residues in mammalian hormones are not always conserved throughout vertebrate evolution.

Conclusions:

  • The distinct hormonal roles of glucagon, GLP-1, and GLP-2 evolved through varying selective pressures.
  • GLP-1's function shifted from a glucagon-like role in fish to an incretin in mammals.
  • Mammalian GLP-2 likely acquired new biological functions during early mammalian evolution.