External seminar - Frédéric Ducongé (CEA)

Abstract : In vitro selection experiments have brought fundamental knowledge of how molecular function can arise from randomly synthesized molecules. It has contributed to strengthen the RNA world hypothesis as well as to develop innovative compounds for diagnostic or therapy. However, the molecular evolution that can happen in a test tube was difficult to access until the recent development of high-throughput sequencing (HTS). This technology has made it possible to study millions of sequences taken at different times during a process of molecular evolution. 

We developed a bioinformatics workflow to analyze these HTS data in successive steps. It can extract and graphically analyze several patterns of molecular evolution. First, an empirical genealogical evolutionary (EGE) tree can be reconstructed to represents the evolution of several aptamer variants from a family. This tree, which was inspired by the diagram published by Charles Darwin, provides the abundance of each variant at different rounds and uses this information, in addition to sequence alignment, to build family relationships between variants. Using this diagram we observed which variations could appear successively to improve an aptamer. This analyse can help to better understand the effect of selection pressure and to optimize aptamer selection.