Single Molecule Genetics: Tiemann-Boege
The research interest of our lab is to study how recombination and mutation is shaping the evolution of our genome. We are using single molecule analysis to accurately characterize recombination hotspots. Homologous meiotic recombination is localized in small regions known as hotspots. Interestingly, we share only a small fraction of hotspots with our closest relative, the chimp.
On a shorter evolutionary scale some hotspots are population-specific, and are highly variable even among different individuals. Models about recombination hotspots are incomplete and controversial with several bizarre findings such as the hotspot paradox, rapid hotspot turnover during evolution and what appear to be heritable shifts in how hotspots are recruited for recombination. In order to understand the mechanisms controlling hotspot activity and its evolution we are addressing the following research questions:
Mutation: Recombination is highly mutagenic based on direct studies in lower order organisms and indirect evidence from sequence comparisons. We are experimentally measuring the mutation frequency associated with homologous meiotic recombination in the human genome. Selection: Recent evidence suggests that recombination hotspots might play a role in the evolution of certain gene classes. Genes involved with external functions seem to have higher recombination rates than genes with intra-cellular functions. We are comparing the activity of different recombination hotspots associated with specific gene classes to test this hypothesis.
In order to study recombination hotspots, we are using a technology called bead-emulsion amplification (BEA) to analyze in parallel millions of single molecule PCR reactions. Single molecules are amplified on microscopic beads in isolation by compartments formed by an emulsion.