Thousands of single-copy internal eliminated sequences (IESs) are excised from the germ line genome of ciliates during development of the polygenomic somatic macronucleus, following sexual events. Paramecium IESs are short, noncoding elements that frequently interrupt coding sequences. No absolutely conserved sequence element, other than flanking 5-TA-3 direct repeats, has been identified among sequenced IESs; the mechanisms of their specific recognition and precise elimination are unknown. Previous work has revealed the existence of an epigenetic control of excision. It was shown that the presence of one IES in the vegetative macronucleus results in a specific inhibition of the excision of the same element during the development of a new macronucleus, in the following sexual generation. We have assessed the generality and sequence specificity of this transnuclear maternal control by studying the effects of macronuclear transformation with 13 different IESs. We show that at least five of them can be maintained in the new macronuclear genome; sequence specificity is complete both between genes and between different IESs in the same gene. In all cases, the degree of excision inhibition correlates with the copy number of the maternal IES, but each IES shows a characteristic inhibition efficiency. Short internal IES-like segments were found to be excised from two of the IESs when excision between normal boundaries was inhibited. Available data suggest that the sequence specificity of these maternal effects is mediated by pairing interactions between homologous nucleic acids.Ciliates are unicellular eukaryotes in which germ line and somatic functions are assumed by two kinds of nuclei coexisting in the same cytoplasm. The diploid micronuclei are transcriptionally silent during vegetative growth; their main function is to provide gametic nuclei upon meiosis. Vegetative transcription takes place in the polygenomic, somatic macronuclei that divide amitotically and are lost soon after meiosis. Following fertilization, both kinds of nuclei differentiate from copies of the diploid zygotic nucleus. Macronuclear development involves extensive rearrangements of the germ line genome: chromosomes are fragmented into shorter, acentric molecules, and tens of thousands of internally eliminated sequences (IESs) are removed from coding and noncoding sequences, in a reproducible and often highly precise manner. In addition, the genome is amplified to the final ploidy level, ϳ1,000n in Paramecium aurelia complex species (for general reviews, see references 5 and 34; for a review of IESs, see reference 19).All known Paramecium IESs are short (26 to 882 bp), ATrich, single-copy elements flanked by 5Ј-TA-3Ј direct repeats in the germ line sequence. Excision invariably leaves one of the TA repeats in the rearranged macronuclear sequence, suggesting that the same basic mechanism is used for all IESs. Although the excision mechanism is currently unknown, reaction products and intermediates have been identified in other ciliate species. In E...