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Genome, the Edited Version: DNA and RNA Editing of Mammalian Retroelements (Gendever)
Start date: Oct 1, 2012, End date: Sep 30, 2017 PROJECT  FINISHED 

It is generally thought that an organism contains the exactly same genomic information in all its cells and that a genome remains unaltered throughout the organism’s life, with the exception of rare and random somatic mutations that might occur. This genomic information will also serve as a template for exact RNA copies. However, endogenous and powerful means of creating inner genomic diversity are known to exist: (1) RNA editing that leads to alteration of one nucleotide into another, (mainly A-to-I); (2) DNA editing that changes the DNA’s content by shifting C-into-U; (3) active retroelements that can insert copies of their sequences into new locations in a genome.Recently, we and others have found that although considered extremely rare, all three mechanisms are active somatically or at least leave traces of their occurrence in the genome, and are linked together, as most editing events occur in retroelements. However, the magnitude and scope of these mechanisms, which can lead to huge diversity and complexity within an organism and even within a cell, are still a mystery. This explosion of genomic variety can have dramatic effect on diverse biological processes, such as brain complexity, cancer and evolution acceleration.In GENEDVER, we aim to perform the first genome-wide mapping of editing and active retroelements in various genomes using a combination of computational and genomic approaches. Specifically, we will develop a strategy to detect RNA and DNA editing in retroelements, scan for editing events in various genomes, and build the first global editing atlas. In addition, we will exploit the close association between editing and retroelements in to produce a genome-wide approach to detect active retroelements. Finally, we will screen for editing events and retrotranspositions in various biological conditions, in order to expose their involvement in many biological states and evolution.

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