Mechanisms of non-LTR retrotransposition
We have long-term interests in understanding the ongoing evolutionary battle between genomic parasites and the host organism, and the cellular programs that have evolved in response to these conflicts. We study Long Interspersed Nuclear Elements (LINEs, or L1) due to their spectacular success in colonizing the human genome. LINEs are retrotransposons, genetic elements that replicate through an RNA intermediate and integrate back into the chromosome. LINEs are responsible for generating over one third of mammalian genome sequence, and LINE retrotransposition causes genome structural variation between human individuals. In addition, transposition is a process that generally occurs in germ cells, and loss of transposon regulation is associated with sterility in model organisms. This is likely due to the genotoxic effects of transposition.
Because of the continual bombardment of our genomes (and the genomes of many other species) with new mutations due to L1-like elements, we have an interest in understanding how these elements replicate and how they are regulated. We have developed a model system for LINE retrotransposition in the budding yeast Saccharomyces cerevisiae. We are using the powerful molecular and genetic tools of yeast to explore interactions between the LINE replication process and the host. In addition, we are modeling the initial acquisition and expansion of repetitive DNA in a naïve host. We are seeking conserved mechanisms that can eventually be manipulated to control transposon activity in vivo (e.g. in humans).