Toward a phylogeny of biological functions.

Karl Schweighofer, Michael New and Andrew Pohorille

The key issue in studying the origin and evolution of life on earth, and the possibilities for the origin of life on other planets, is to determine how essential cellular functions developed, were performed and became integrated into a simple cell. The best approach to this problem is to exploit our knowledge of presently living organisms and their antiquity. This is the subject of evolutionary biology and is largely pursued by constructing evolutionary (phylogenetic) trees, which describe evolutionary relations between different organisms. These trees are based on the sequence of nucleic acids encoding different genes. Unfortunately, the knowledge of phylogenetic trees yields only very limited information about three-dimensional structures of proteins, their functions and evolution. Since it is the three-dimensional structure that is directly related to protein functionality, we currently cannot systematically study how new biological functions arose, evolved and became integrated into extant metabolic networks.

Our goal is to develop novel computational approaches, based on modern information theory, for incorporating sequence, structural and functional information about a group of proteins into a single representation, and for using this representation to answer fundamental questions about evolutionary relationships between the proteins and their functions. This approach will be used to elucidate the evolutionary history of ligand-gated ion channels and their relationship to other ion channel proteins.

LGICs are particularly suitable models because their origin and evolution, as inferred from current methods, is uncertain, but should become much clearer once additional information about sequence, structure pharmacology, etc. is incorporated. LGICs are a super-family of protein assemblies which transport ions accross cell membranes in response to the presence of specific chemicals in the environment. They are present in a diverse range of species, from nematodes to humans, and are estimated to have diverged from an unknown common ancestor 2-2.5 billion years ago.