Proteins capable of self-perpetuating changes in conformation and function
(known as prions) can serve as genetic elements. To test whether novel prio
ns could be created by recombinant methods, a yeast prion determinant was f
used to the rat glucocorticoid receptor. The fusion protein existed in diff
erent heritable functional states, switched between states at a Low spontan
eous rate, and could be induced to switch by experimental manipulations. Th
e complete change in phenotype achieved by transferring a prion determinant
from one protein to another confirms the protein-only nature of prion inhe
ritance and establishes a mechanism for engineering heritable changes in ph
enotype that should be broadly applicable.