The Eickbush laboratory studies the mechanism of integration, cellular control, and population genetics of mobile elements that insert specifically into the 28S rRNA genes of their hosts. Most of our work focuses on the R2 retrotransposon; elements found in animals as diverse as vertebrates, arthropods, and hydra. Our early biochemical studies of the proteins encoded by R2 revealed a new mechanism of insertion (retrotransposition) in which the element's RNA transcript is directly reverse transcribed using the chromosomal target site as primer. A large family of mobile elements, the non-LTR retrotransposons, is now thought to use this Target Primed Reverse Transcription (TPRT) mechanism. Non-LTR retrotransposon insertions have had dramatic effects on the evolution and current functioning of eukaryotic genomes. For example, the TPRT mechanism has been estimated to account for 40% of the DNA in the human genome.
Strong selective pressure should eliminate R2 elements from the rDNA locus, because every R2 insertion blocks the production of functional 28S rRNA. Individual R2 copies are rapidly eliminated by the frequent recombination events that lead to the concerted evolution of the rRNA genes. However, studies of the abundance of R2 elements within populations, as well as the phylogenetic studies of R2 elements in different species, suggest R2 elements are seldom completely lost, and as a group undergo highly stable transmission over millions of years. Our current studies focus on the balance that must exist between the rate of new R2 insertions to preserve the element and their rate of loss by recombination and selection. We are also dissecting the mechanisms that control R2 activity using active and inactive lines of Drosophila. R2 elements are co-transcribed with the rRNA genes and are processed from this co-transcript by a self-cleaving ribozyme encoded at the 5’ end of R2. Primary control over R2 is at the level of transcription of the rDNA unit. Our studies have shown that R2 transcription is influenced by the genes involved in heterochromatin formation, but ultimately it is the distribution of R2-inserted units in the rDNA locus that controls whether R2-inserted units are transcribed. Current studies are designed to determine both when and how the R2 protein is translated from the self-cleaved RNA, and thus when during development R2 elements retrotranspose. For more information go to our lab website http://blogs.rochester.edu/EickbushLab/