Genomes are constantly under threat from transposons: “selfish” DNA sequences that can copy themselves independently of the replication of the genome. Left unchecked accumulation of transposon copies within the genome can disrupt essential gene functions, thus placing enormous selective pressure on organisms to evolve robust defense mechanisms to shut down the expression of transposons and reduce their spreading. However, transposons may not always be detrimental: there are many examples where transposon insertions appear to have contributed positively to the evolution of species. Thus transposon-silencing pathways have to control their targets without completely stifling evolutionary novelty. Our aim is to understand how organisms regulate transposon-silencing pathways to achieve this balance and what happens if this regulation fails.
To study mechanisms of transposon silencing we use the simple, genetically tractable nematode Caenorhabditis elegans, along with a variety of related nematodes, as a model system to which we apply comparative genomics, computational modeling and in lab evolution. Our particular interest is the Piwi-interacting (piRNA) pathway, conserved from nematode worms to mammals, in which small RNAs called piRNAs seek out transposon RNAs through base-pairing interactions and target them for transcriptional and post-transcriptional silencing. Transcriptional silencing triggered by piRNAs establishes epigenetic changes, which can last for several generations in the absence of the initial piRNA itself (See Figure 1). By studying the piRNA pathway in C. elegans we hope to understand the fundamental mechanisms of transposon control in animals, and how transgenerational epigenetic inheritance initiated by piRNAs might contribute to adaptation and evolution.
Transgenerational inheritance of piRNA mediated silencing in C. elegans. In wild type animals, piRNAs bound by the Piwi protein PRG-1 instigate the formation of further small RNAs (22Gs) against target RNAs. When the piRNA pathway is removed, the 22Gs can maintain themselves for several generations; however eventually this decays leading to accumulation of repetitive RNA and infertility. Interestingly though, mutation of the insulin receptor homologue daf-2 can restore fertility by potentiating an alternative, piRNA independent silencing pathway.
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