Ancestral sequence reconstruction as a tool to understand natural history and guide synthetic biology: realizing and extending the vision of Zuckerkandl and Pauling
Ancestral sequence reconstruction as a tool to understand natural history and guide synthetic biology: realizing and extending the vision of Zuckerkandl and Pauling
The perspective on natural history and medicine by Emile Zuckerkandl combined with the chemical expertise of Linus Pauling generated many novel ideas concerning molecular evolution. These included generating multiple sequence alignments, determining phylogenetic relationships based on sequence data, formulating the molecular clock hypothesis, and the proposal to resurrect ancestral sequences based on information contained within extant sequences, inter alia. Although the field of ancestral sequence reconstruction is still burgeoning, the concepts guiding the field are embraced by today's community more so than when originally proposed by Zuckerkandl and Pauling. This chapter presents a view of the field of ancestral sequence reconstruction, including recognition that genes are dynamic fossils in that they record ancient events while still adapting to new environments. It concludes with a discussion of the potential of combining ancestral sequence space and synthetic biology to expand protein functionality for directed evolution studies.
Keywords: Emile Zuckerkandl, Linus Pauling, multiple sequence alignmens, phylogentic relationships, molecular clock hypothesis, genes, protein functionality
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