Transgenerational epigenetic inheritance: adaptation, genome stability and evolution. (360G-Wellcome-104640_Z_14_Z)

Transgenerational epigenetic inheritance: adaptation, genome stability and evolution Since Weismann formulated the distinction between innate and acquired characteristics in the 19th century, the debate about the inheritance of acquired traits has raised many controversies in the scientific community. Following convincing arguments against, e.g. by William Bateson, this debate was then largely set aside. However, a number of phenomena and epigenetic mechanisms involving RNA, histone modificat ion or DNA methylation have renewed interest in this area. Transgenerational epigenetic effects likely have wide-ranging implications for human health, biological adaptation and evolution, however their mechanisms remain poorly understood. We recently demonstrated that a germline nuclear RNA and chromatin pathway maintains gene silencing stably for many generations in the nematode Caenorhabditis elegans. We hypothesise that transgenerational epigenetic inheritance (TEI) is the consequence of interactions between repetitive and genic parts of the genome mediated by small RNA. We will investigate the mechanisms underlying TEI, determine if and how TEI provides an environmental memory (Lamarckism) and examine its implications for genome stability and evolution. Our questions are: Q1. What are the mechanisms underlying transgenerational epigenetic inheritance? Q2. How does the environment shape the transgenerational epigenetic landscape to anticipate the phenotype of the next gen eration? Q3. How do transgenerational epigenetic effects shape the distributions of the genetic and epigenetic landscape of populations? We will use the powerful molecular genetic tools available for C. elegans, an animal with a generation time of three days and a genome 1/30 the size of the human genome. In addition, we will take advantage of recent advances in induced pluripotent stem cell (iPS) technology to translate our work to humans.