Paramecium tetraurelia, stock d 1 13, although completely homozygous, produces t w o kinds of genomically identical clones: N (nondischarge) clones incapable of trichocyst exocytosis (discharge) from intact cells in response t o picric acid; and D (discharge) $ones that d o respond. These alternatives are irreversibly determined (at 27 C) during a determination sensitive period the first day after fertilization (autogamy, conjugation, or cytogamy): D parents are always determined t o produce D progeny; N parents produce mostly N progeny if kept in exhausted medium, but mostly D progeny if kept in bacterized nutrient medium, throughout the sensitive period. If connecting bridges between mates persist long after the time for pair separation, t h e N member of N X D conjugant and cytogamous pairs produces D progeny even if exposed t o exhausted medium throughout t h e sensitive period, thus indicating the presence in D mates of a D-determining cytoplasmic factor,A, which overrides effects of external conditions. N and D determinations are brought about o n newly developing somatic nuclei (macronuclear anlagen). After macronuclear development has been completed, determination is irreversible in it and its descendant macronuclei. M (mixed) clones produce N , D, and partial D cells; within these clones, diverse subclones can be selected. Crosses of d113 (N) X standard wild stock 5 1 (D) yield n o segregation in F,, indicating no genomic difference between d113 (N) and wild t y p e (D). A may be a genic product regulating its o w n production. This results in "cytoplasmic inheritance" of D vs N in crosses of D X N followed by exhausted medium during t h e sensitive period. As with t h e only other well-analyzed comparable example, mating types, neither a genetic nor an epigenetic interpretation has yet been excluded for this system of developmental differentiation.
Sonneborn and Schneller
INTRODUCTIONWe present in this paper an example of alternative hereditary phenotypes in cell lineages that have identical and completely homozygous genotypes and that are cultured under identical external conditions. These hereditary alternatives are nevertheless determined by the nucleus as nuclear differentiations that can be brought about only during a limited period of less than one day in tlie whole clonal life cycle, a period responsive to irreversible determining action of external and internal factors. We intend to report further study and analysis of each of the features of this system in a series of later papers. Here we attempt to give only an overview of the system with supporting data.The chief interest of systems of this kind lies in their phenomenological similarity to those normal cellular differences that commonly arise during development of multicellular animals and are highly stable during long culture as explants. The existence o f at least superficially similar clonal systems in unicellular organisms has long been known and has been frequently reviewed [ 1-91 . To the extent that underlying mechanisms have been d...