ABI Innovation: Co-evolution of domains, genes and species: models, algorithms, and software

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An award is made to Carnegie Mellon University to develop evolutionary models, algorithms, and software for multidomain protein families. These families evolve through the insertion, duplication, and deletion of domains, sequences that encode discrete structural units that are the building blocks of protein function. The emergence of novel domain combinations drives the evolution of functional variation and interaction specificity in protein families that perform core molecular functions. Multidomain families are of central importance throughout life. In bacteria, multidomain families encode the two-component kinase signaling systems that are the back-bone of cellular communication. In eukaryotes, multidomain families are implicated in tissue repair, cell death, inflammation response, antigen recognition, and innate immunity. This project will develop a computational framework for reconstructing the evolutionary history of a multidomain family, including the domain events that gave rise to present-day proteins, the ancestral domain architectures from which they evolved, and a tree describing the history of the family as a whole. This new framework will comprise a formal, event-based model of multidomain family evolution; algorithms for inferring domain events and the ancestral domain content of a given family; and an implementation of these algorithms in prototype software for inference and visualization of multidomain protein histories. Because this approach considers domain sequence, as well as domain content, and incorporates an explicit model of events, it promises a dramatic increase in accuracy and detail. The results of this project will enable evolutionary biologists to investigate the processes of protein evolution, bench biologists to identify appropriate experimental targets, and cell biologists to complement experimental results with evolutionary analyses. This project will contribute to educational resources through the development of teaching materials on multidomain evolution for an undergraduate course, a graduate course, and a workshop on "Developing Bioinformatics Programs at Minority Schools." This one week workshop is part of a Pittsburgh Supercomputing Center initiative to develop new bioinformatics programs at minority-serving institutions. This project will also provide research training for undergraduate and graduate students at the interface between biology and computer science.