Evolution of Retrotransposon Control Mechanisms

PROJECT SUMMARY/ABSTRACT Evolution of Retrotransposon Control Mechanisms Dysregulated expression of retrotransposons and other transposable elements (TEs) can lead to increases in TE copy number, DNA damage and instability, or aberrant regulation of host genes, which in turn can contribute to human disease. Conversely, TE activity is required for processes ranging from early mammalian development and cell senescence to horizontal transposon transfer (HTT) between species. The natural downregulation or absence of TE defense mechanisms such as RNA interference, DNA methylation, and repressive chromatin provides opportunities for TE expression and mobility. The fact that TEs do not always proliferate unchecked in such cases suggests new mechanisms of TE control remain to be discovered. The Saccharomyces cerevisiae/Ty paradigm is an attractive model for discovering new types of retrotransposon control. S. cerevisiae and its close relative S. paradoxus lack canonical TE control pathways but contain multiple active yet restrained retrotransposon families (Ty1-Ty5). We will expand on our discovery of a self-encoded form of copy number control (CNC) for the canonical Ty1 element (Ty1c) to determine if other Ty elements undergo forms of CNC, systematically determine whether Ty family interactions influence mobility, define the origin of Ty1c CNC, and understand the evolution and function of endogenized Ty sequences. In addition, we will develop new experimental models to study the mechanisms and consequences of HTT between species. Our work will combine rigorous experimental and computational approaches to provide insight into how novel mechanisms of retrotransposon regulation function and evolve to limit TE mobility and HTT.