Non-Mendelian inheritance and homology-dependent effects in ciliates

Ciliates are single-celled eukaryotes that harbor two kinds of nuclei. The germline micronuclei function only to perpetuate the genome during sexual reproduction; the macronuclei are polyploid, somatic nuclei that differentiate from the micronuclear lineage at each sexual generation. Macronuclear development involves extensive and reproducible rearrangements of the genome, including chromosome fragmentation and precise excision of numerous internal sequence elements. In Paramecium and Tetrahymena, homology-dependent maternal effects have been evidenced by transformation of the vegetative macronucleus with germline sequences containing internal eliminated sequences (short single-copy elements), which can result in a specific inhibition of the excision of the homologous elements during development of a new macronucleus in the sexual progeny of transformed clones. Furthermore, transformation of the Paramecium maternal macronucleus with cloned macronuclear sequences can specifically induce new fragmentation patterns or internal deletions in the zygotic macronucleus. These experiments show that the processing of many germline sequences in the developing macronucleus is sensitive to the presence and copy number of homologous sequences in the maternal macronucleus. The generality and sequence specificity of this transnuclear, epigenetic regulation of rearrangements suggest that it is mediated by pairing interactions between zygotic sequences and sequences originating from the maternal macronucleus, presumably RNA molecules. Alternative macronuclear versions of the genome can be maternally inherited across sexual generations, suggesting a molecular model for some of the long-known cases of non-Mendelian inheritance, and in particular for the developmental determination and maternal inheritance of mating types in Paramecium tetraurelia.