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Darwinian evolution of prions in cell culture

Jiali Li1, Shawn Browning, Sukhvir P Mahal

  • 1Department of Infectology, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, USA.

Science (New York, N.Y.)
|January 2, 2010
PubMed

Insights

Prions, infectious proteins, exhibit mutation and selection similar to organisms with genes. Different prion strains adapt to environments like cell cultures versus brains, demonstrating evolutionary principles.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Prion Biology

Background:

  • Prions are infectious proteins, primarily PrP(Sc), a misfolded form of PrP(C).
  • Prion strains are believed to be determined by PrP(Sc) conformation.
  • Prions lack a nucleic acid genome.

Purpose of the Study:

  • To investigate prion mutation and selection dynamics.
  • To understand how prion populations evolve under different conditions.

Main Methods:

  • Biologically cloned prion populations were monitored for heterogeneity.
  • Selective pressures, including host environment (brain vs. cell culture) and drug inhibition (swainsonine), were applied.
  • Prion adaptation and outgrowth were assessed.

Main Results:

  • Cloned prion populations accumulated mutations, becoming heterogeneous.
  • Cell-adapted prions outcompeted brain-adapted prions in cell cultures, and vice versa.
  • Swainsonine selected for resistant prion substrains, while its absence favored susceptible substrains.

Conclusions:

  • Prions, despite lacking a genome, undergo mutation and selective amplification.
  • Prion evolution is influenced by environmental pressures and host adaptation.
  • This suggests evolutionary principles apply to non-genetic infectious agents.

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