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

Abstract

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. 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. We now show that clusters of P-element-derived transgenes that induce strong TSE 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 gene involved in siRNA production. The paramutated cluster, previously producing barely detectable levels of piRNAs, is converted into a stable, strong piRNA-producing locus by the paramutation and becomes fully paramutagenic itself. Our work provides a genetic model for the emergence of piRNA loci, as well as for RNA-mediated trans-generational repression of transposable elements.

Could interallelic interactions be a key to the epigenetic aspects of fitness-trait inbreeding depression?

“…One important characteristic of these ICRs is that the maternally methylated ICRs can either exert promoter activity on the paternal allele or silence it (Haun et al, 2009). This kind of interallelic talk resembles the paramutations that have been reported in plants and in the mouse, and more recently in Drosophila (de Vanssay et al, 2012). In these paramutations the two parent-oforigin alleles can influence one another's expression; these epigenetic modifications are known to be transmitted to the offspring, and have been shown to be triggered by changing epigenetic states of TEs in maize (Goettel and Messing, 2013).…”

Guest list or black list: heritable small RNAs as immunogenic memories

“…Unlike maternally-inherited proteins, which dilute quickly over generations, piRNAs are amplifiable, and the maternally-deposited piRNAs in flies persist long into adulthood [39]. Moreover, amplification mechanisms allow piRNAs to establish multigenerational defense against a variety of selfish elements [26,28,40,41]. piRNA amplification is achieved by different mechanisms in different organisms.…”

“…Long-term piRNA inheritance appears to be well conserved: recently it was shown that piRNAs are inherited for 50 generations in Drosophila [40], and for at least two generations in Danio rerio [44]. While piRNAs are involved in many inherited immunity effects, they are obviously not central to all such mechanisms.…”

Paramutation inDrosophilaRequires Both Nuclear and Cytoplasmic Actors of the piRNA Pathway and InducesCis-spreading of piRNA Production

“…This cluster shows a low level of variegation at 25°but variegation is stronger at higher temperatures presenting almost a fully white phenotype at 29°(data not shown). DX1 has no trans-silencing capacities (Ronsseray et al 2001;de Vanssay et al 2012). The two reciprocal crosses were first performed between DX1 and w 1118 ; Cy/Xa individuals to test for the existence of a maternal effect of DX1 inheritance on its eye phenotype and no significant difference was observed between the two types of progeny for white expression ( Figure 5B).…”