Paramutation in Drosophila linked to emergence of a piRNA-producing locus

• Published in: Nature (London) 2012-10, Vol.490 (7418), p.112-115
• Main Authors: de Vanssay, Augustin, Bougé, Anne-Laure, Boivin, Antoine, Hermant, Catherine, Teysset, Laure, Delmarre, Valérie, Antoniewski, Christophe, Ronsseray, Stéphane
• Format: Article
• Language: English
• Subjects: 631/208/176; 631/337/384/2054; Alleles; Analytical, structural and metabolic biochemistry; Animals; Bioinformatics; Biological and medical sciences; Computer Science; Cytoplasm; Cytoplasm - genetics; DNA methylation; DNA Transposable Elements - genetics; Drosophila; Drosophila melanogaster - genetics; Drosophila Proteins - deficiency; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Epigenetics; Extrachromosomal Inheritance - genetics; Female; Fundamental and applied biological sciences. Psychology; Gene Silencing; Genetic aspects; Genetic engineering; Genetic Loci - genetics; Genetics; Genomes; Germ Cells - metabolism; Humanities and Social Sciences; Identification and classification; Insects; letter; Life Sciences; Male; Models, Genetic; Molecular and cellular biology; multidisciplinary; Multigene Family - genetics; Mutation; Observations; Ovary - metabolism; Paramutation; Peptide Initiation Factors - deficiency; Peptide Initiation Factors - genetics; Peptide Initiation Factors - metabolism; Quantitative Methods; Ribonuclease III - deficiency; Ribonuclease III - genetics; RNA; RNA Helicases - deficiency; RNA Helicases - genetics; RNA, Small Interfering - biosynthesis; RNA, Small Interfering - genetics; Science; Science (multidisciplinary); Transgenes - genetics
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature11416

A paramutation occurs between two alleles in the same locus, when one allele induces a heritable mutation in another allele without modifying the DNA sequence; now, in Drosophila , a paramutation is shown to be transmissible over generations. Paramutations transmissible in the fruitfly Paramutations are epigenetic interactions between two alleles at a given locus, in which one allele induces a heritable modification of the other without modifying the DNA sequence. Working in Drosophila , Augustin de Vanssay et al . show that clusters of P -element-derived transgenes that induce a strong trans -silencing effect (TSE) can convert other homologous transgene clusters incapable of TSE into strong silencers, which in turn transmit the acquired silencing capacity. The paramutation is mediated by maternal inheritance of cytoplasm-carrying Piwi-interacting RNAs (piRNAs) homologous to the transgenes. They show that the paramutated cluster is converted into a stable, strong piRNA-producing locus and becomes fully paramutagenic itself. Thus the authors provide a genetic model for the emergence of piRNA loci, as well as for RNA-mediated trans-generational repression of transposable elements. A paramutation is an epigenetic interaction between two alleles of a locus, through which one allele induces a heritable modification in the other allele without modifying the DNA sequence 1 , 2 . The paramutated allele itself becomes paramutagenic, that is, capable of epigenetically converting a new paramutable allele. Here we describe a case of paramutation in animals showing long-term transmission over generations. We previously characterized a homology-dependent silencing mechanism referred to as the trans -silencing effect (TSE), involved in P -transposable-element repression in the germ line 3 , 4 , 5 . We now show that clusters of P -element-derived transgenes that induce strong TSE 6 , 7 can convert other homologous transgene clusters incapable of TSE into strong silencers, which transmit the acquired silencing capacity through 50 generations. The paramutation occurs without any need for chromosome pairing between the paramutagenic and the paramutated loci, and is mediated by maternal inheritance of cytoplasm carrying Piwi-interacting RNAs (piRNAs) homologous to the transgenes. The repression capacity of the paramutated locus is abolished by a loss-of-function mutation of the aubergine gene involved in piRNA biogenesis, but not by a loss-of-function mutation of the Dicer-2