Phylogenetic Investigation on the Evolution of the Secretary Apparatus

Molecular functions are result of the functional and structural communication between protein interfaces and these interfaces are maintained by the action of evolutionary pressure on the regions of the interacting proteins that contribute to binding. During the course of evolution, proteins undergo variability in their sequence due to spontaneous mutations. However, this variability should not affect the basic structure and function of the protein. Selection restricts amino acid replacements, accounting for the conservation of binding interfaces. So changes or mutations in one protein will be mitigated by compensatory change in its binding partner, maintaining function in the face of evolutionary change. Such coordinated mutations in proteins are thought to occur since there is a stronger selective pressure to maintain protein structure and function than sequence. Thus, the proteins involved in complex interactions undergo co-evolution to maintain functional and structural complementarity.

Correlated mutations or co-evolutionary studies can be performed in sequence evolution to predict interactions of proteins. This approach involves use of sequences to identify correlations by different approaches and so infer probable binding. However, other factors such as shared evolutionary history and similarities in the rates of evolution confound these whole-sequence–based approaches. The study of these coevolving residues could give an insight to the structurally and functionally important residues. A large number of bioinformatics tools and programs have been developed for the prediction of coevolving residues, given a query sequence or a multiple sequence alignment of orthologous sequences. However, all of them have some or the other limitations.

We aim to develop a program for detection of co-evolution in protein interactions that can overcome the limitations of the previous approaches. Ultimately, we want to use the developed program for detection and study of the co-evolutionary patterns in the evolutionary history of the SNARE protein, so as to identify the key elements of the prototypic fusion mechanism and to pinpoint its functionally important sites. This will help us to establish a detailed evolutionary and functional description of the “SNARE interaction network”. In addition, we want to uncover how the interaction network has adapted in different eukaryotic lineages and how it was most probably organized in the proto-eukaryotic cell. This will enable us to understand the fundamental mechanism of the vesicle fusion in a better way.