Darwinian evolution of prions in cell culture.
Prions are infectious proteins consisting mainly of PrP(Sc), a beta sheet-rich conformer of the normal host protein PrP(C), and occur in different strains. Strain identity is thought to be encoded by PrP(Sc) conformation. We found that biologically cloned prion populations gradually became heterogeneous by accumulating "mutants," and selective pressures resulted in the emergence of different mutants as major constituents of the evolving population. Thus, when transferred from brain to cultured cells, "cell-adapted" prions outcompeted their "brain-adapted" counterparts, and the opposite occurred when prions were returned from cells to brain. Similarly, the inhibitor swainsonine selected for a resistant substrain, whereas, in its absence, the susceptible substrain outgrew its resistant counterpart. Prions, albeit devoid of a nucleic acid genome, are thus subject to mutation and selective amplification.
Li
Jiali
J
Department of Infectology, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, USA.
Browning
Shawn
S
Mahal
Sukhvir P
SP
Oelschlegel
Anja M
AM
Weissmann
Charles
C
D000818:Animals; D001923:Brain Chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D003470:Culture Media; D017077:Culture Media, Conditioned; D019143:Evolution, Molecular; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D018620:PrPSc Proteins / Q000737:chemistry / Q000145:classification / Q000472:pathogenicity; D017096:Prion Diseases; D011328:Prions / Q000737:chemistry / Q000145:classification / Q000472:pathogenicity* / Q000502:physiology*; D011487:Protein Conformation; D017026:Swainsonine / Q000494:pharmacology
D003470:Culture Media; D017077:Culture Media, Conditioned; D018620:PrPSc Proteins; D011328:Prions; D017026:Swainsonine