Dr. Thomas LaBean
Duke University

Co-Investigators

Erik A. Schultes, Duke University
Peter Hraber, Los Alamos National Lab

Project Title

Experimentally Probing the Origins of Macromolecular Structure

Project Summary

Darwin's theory of evolution describes the close fit between adaptations and the environment, but what is the ultimate source of these adaptations from which natural selection must choose? For macromolecules such as proteins and the nucleic acids RNA and DNA, no amount of genomic or phylogentic data can answer this question because genealogical relationships among macromolecules confound the ultimate physiochemical properties creating adaptations and the historically contingent constraints that limit them. To understand the ultimate origins of macromolecular structures, it is therefore necessary to explore the much larger space of sequence possibilities from which particular evolutionary lineages are derived. This FQXi proposal will utilize new technology to literally "print" tens-of-thousands of closely-related DNA sequences on a "chip" so their functional adaptations can be directly analyzed using automated instrumentation. By systematically scanning through large regions sequence space, it will be possible to identify the entire spectrum of adaptations that are possible and to directly evaluate the likelihood that new structures and functions can emerge in the course of evolution. This experimental approach opens up a new kind of evolutionary analysis based not on what has happened in the past, but what is possible independent of any particular evolutionary lineage.



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