Defining the shape of evolutionary landscapes

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It is possible to infer the past by observing the diversity of genes that exist today only if we understand the mechanics of diversification. In the case of genes and their products, we call this diversification "evolution". We further represent the natural history of genes using phylogenetic trees: where each leaf is an observation, each bifurcation an assumed ancestor to its leaves, and the root being the last common ancestor to all leaves. This proposal is about the rigorous understanding of how the most likely tree can be found, and about the meaning of trees inferred from the 3D structures of proteins. If we are given the amino acid sequence of a number of related genes and the topology (shape) of a tree, it is possible to compute how likely this tree fits the sequence data. The main difficulty is to find the most likely topology amongst an extremely large number of others. This research looks at all possible trees as an optimisation landscape which has to be searched for the best solution. We are proposing to develop tools to define, visualise and explore landscapes. With these, we will be able to understand why finding the most likely tree is so difficult. If we understand better the problem, we can improve on the solution and positively affect all bioinformatics methods that rely on a tree to predict functions, classify organisms, or discover new knowledge. Studying protein sequence data has been done for years. The shape of the tree often reflects the diversification of proteins through inheritance and duplication. The mechanism of evolution of the 3D structures encoded by these sequences is not as well understood. In this program, we are using the well defined methodologies of inferring sequence trees to build phylogenies of protein structures. The kind of stories told by these trees will be very different, reaching possibly to much ancient events in evolutionary time. This is because structures do not evolve as quickly as sequences. Reconstructing events of structural diversification is especially challenging since there are reasons to believe that structures do not always evolve in a tree-like fashion. This makes their natural histories more similar to the evolution of whole bacterial genomes.