Sequences related to transposons constitute a large fraction of extant genomes, but insertions within coding sequences have generally not been tolerated during evolution. Thanks to their unique nuclear dimorphism and to their original mechanism of programmed DNA elimination from their somatic nucleus (macronucleus), ciliates are emerging model organisms for the study of the impact of transposable elements on genomes. The germline genome of the ciliate Paramecium, located in its micronucleus, contains thousands of short intervening sequences, the IESs, which interrupt 47% of genes. Recent data provided support to the hypothesis that an evolutionary link exists between Paramecium IESs and Tc1/mariner transposons. During development of the macronucleus, IESs are excised precisely thanks to the coordinated action of PiggyMac, a domesticated piggyBac transposase, and of the NHEJ double-strand break repair pathway. A PiggyMac homolog is also required for developmentally programmed DNA elimination in another ciliate, Tetrahymena. Here, we present an overview of the life cycle of these unicellular eukaryotes and of the developmentally programmed genome rearrangements that take place at each sexual cycle. We discuss how ancient domestication of a piggyBac transposase might have allowed Tc1/mariner elements to spread throughout the germline genome of Paramecium, without strong counterselection against insertion within genes. 1. Introduction Since the initial evidence for the existence of transposable elements (TEs) reported by McClintock [1], large-scale sequencing of the genome of a wide range of living organisms has highlighted the abundance of TE-derived sequences relative to the coding portion of genomes. Transposable elements, often considered as “selfish” or “parasitic” DNA, are mobile genetic elements that encode their own mobility enzymes and move from one genomic locus to another. Based on their transposition mechanisms, they can be classified into two main categories [2, 3]: class I elements transpose via the reverse transcription of an RNA molecule, while class II elements transpose via a DNA intermediate. Class II transposons, also called DNA transposons, are found in variable proportions among eukaryotic and prokaryotic genomes; for instance, they constitute the major fraction of resident TEs in bacteria (reviewed in [4]) but are underrepresented relative to class I elements in the human genome [5] and absent from the genome of the yeast Saccharomyces cerevisiae [6]. Among DNA transposons, cut-and-paste transposons move in two steps: (i) excision
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