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Evolution of hormone-receptor complexity by molecular exploitation.

Jamie T Bridgham1, Sean M Carroll, Joseph W Thornton

  • 1Center for Ecology and Evolutionary Biology, University of Oregon, Eugene, OR 97403, USA.

Science (New York, N.Y.)
|April 8, 2006
PubMed
Summary

Evolutionary biology explains complex systems through natural selection. This study shows how the mineralocorticoid receptor

Area of Science:

  • Evolutionary Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Darwinian theory posits that biological complexity arises through gradual adaptation and natural selection.
  • Highly integrated biological systems, where components depend on each other, pose a challenge to understanding stepwise evolutionary origins.
  • The specific interaction between aldosterone and the mineralocorticoid receptor exemplifies such a tightly integrated system.

Purpose of the Study:

  • To investigate the evolutionary pathway of the aldosterone-mineralocorticoid receptor interaction.
  • To demonstrate how complex molecular interactions can evolve via a Darwinian stepwise process.
  • To elucidate the role of molecular exploitation in the evolution of functional partnerships.

Main Methods:

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  • Ancestral gene resurrection techniques were employed to reconstruct ancient receptor variants.
  • The binding affinity of resurrected ancestral receptors to aldosterone and related ligands was experimentally assessed.
  • Site-directed mutagenesis was used to introduce specific amino acid changes into ancestral receptor sequences.

    • Main Results:

    • The ancestral mineralocorticoid receptor exhibited inherent affinity for aldosterone, predating the hormone's evolution.
    • This affinity was a byproduct of the receptor's interaction with chemically similar, ancestral ligands.
    • Introducing just two specific amino acid substitutions in the ancestral receptor recreated the specificity of the modern receptor.

    Conclusions:

    • Complex molecular interactions, like the aldosterone-receptor partnership, can evolve through a stepwise Darwinian process.
    • Molecular exploitation, where existing molecular structures are repurposed for new functions, is a key mechanism for evolving integrated systems.
    • This study provides a molecular basis for understanding the evolution of hormone-receptor specificity and complex biological machinery.