A Transforming Principle

ϩ ] (Wickner, 2001). [PSI ϩ ] is hereditary by classical Cambridge, Massachusetts 02142 genetic criteria—[PSI ϩ ] is transmitted from parents to their progeny both in somatic divisions (mitosis) and in Transformation continues to provide the most compelling evidence that DNA is genetic material. A purified sexual divisions (meiosis). A cross of [PSI ϩ ] by [psi Ϫ ] results in all [PSI ϩ ]progeny. Although these breeding molecule of DNA can be taken up by an organism, propagated , and passed down from generation to generation, experiments demonstrated that the [PSI ϩ ] factor is not chromosomal DNA, the actual molecule responsible for forever changing the heredity of the recipient and its descendants. When the introduced DNA changes a trait [PSI ϩ ]-based inheritance remained obscure. What was missing was vertical transmission, isolation of a mole-of the recipient cell, the cell is said to be " transformed. " Remarkably, several recent experiments with the same cule that could transform a [psi Ϫ ] organism to [PSI ϩ ]. The identification of a protein as the key molecule in formal structure as these DNA experiments lead to the conclusion that protein can also transform cells (Sparrer [PSI ϩ ] inheritance set the stage for this transformation experiment. The yeast prion [PSI ϩ ] results from self-et al., 2000; Maddelein et al., 2002). The protracted saga of transformation began in 1928 propagating aggregation of Sup35p (Glover et al., 1997), a protein required for efficient termination of translation. when F. Griffith, a British army surgeon, reported that an avirulent strain of the pneumococcus bacterium In the [psi Ϫ ] state, the Sup35p is unaggregated and active , whereas in the [PSI ϩ ] state it is aggregated and could be converted to a virulent strain using an extract of heat-killed virulent pneumococcus (Griffith, 1928). As inactive. The [PSI ϩ ] aggregates of Sup35p enhance the ability of ribosomes to read through nonsense muta-bacterial genetics had not yet been discovered, the transformation of an avirulent to a virulent bacterium by tions. This ability of [PSI ϩ ] to suppress nonsense mutations provides a clear-cut assay that distinguishes [PSI ϩ ] some inanimate material was burdened with the stigma of alchemy—in the vernacular of that time, the metamor-from [psi Ϫ ] cells. The [PSI ϩ ] prion propagates when a misfolded version of the Sup35 protein templates the phosis of one species into …