Prion variant generation by cross-seeding could overcome species barriers to prion transmission. (a) An altered form (a 'mutant') of mouse scrapie strain 139A is selected by the high species barrier encountered when it is transferred to hamsters (modified from ). (b) The species barrier between the S. cerevisiae Sup 35 prion [PSI+] and a chimeric protein with a P. methanolica Sup35 prion domain results in the rare generation of either of two [CHI+
] prion variants of the latter on exposure to [PSI+] . (c) Schematic diagram showing partial templating by species A amyloid filament of species B protein. Species B protein sequence is incompatible with all of species A filament structure, and so assumes an altered self-propagating form – a prion variant.