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Published online on January 23, 2008, 10.1073/pnas.0709132105
PNAS | March 25, 2008 | vol. 105 | no. 12 | 4601-4608


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Chemical Ecology Special Feature
CHEMICAL ECOLOGY SPECIAL FEATURE / PERSPECTIVE
The evolution of gene collectives: How natural selection drives chemical innovation

Michael A. Fischbach, Christopher T. Walsh, and Jon Clardy*

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115

Edited by Jerrold Meinwald, Cornell University, Ithaca, NY, and approved November 2, 2007 (received for review October 3, 2007)

DNA sequencing has become central to the study of evolution. Comparing the sequences of individual genes from a variety of organisms has revolutionized our understanding of how single genes evolve, but the challenge of analyzing polygenic phenotypes has complicated efforts to study how genes evolve when they are part of a group that functions collectively. We suggest that biosynthetic gene clusters from microbes are ideal candidates for the evolutionary study of gene collectives; these selfish genetic elements evolve rapidly, they usually comprise a complete pathway, and they have a phenotype—a small molecule—that is easy to identify and assay. Because these elements are transferred horizontally as well as vertically, they also provide an opportunity to study the effects of horizontal transmission on gene evolution. We discuss known examples to begin addressing two fundamental questions about the evolution of biosynthetic gene clusters: How do they propagate by horizontal transfer? How do they change to create new molecules?

Author contributions: M.A.F., C.T.W., and J.C. wrote the paper.

The authors declare no conflict of interest.

*To whom correspondence should be addressed. E-mail: jon_clardy{at}hms.harvard.edu

© 2008 by The National Academy of Sciences of the USA


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