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PEDS Advance Access published online on July 25, 2006
Protein Engineering Design and Selection, doi:10.1093/protein/gzl029
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© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received May 2, 2006
Revised June 19, 2006
Accepted June 22, 2006

Review

Natural history as a predictor of protein evolvability

Taryn L. O'Loughlin 1, Wayne M. Patrick 1, and Ichiro Matsumura 1 *

1 Department of Biochemistry, Center for Fundamental and Applied Molecular Evolution, Emory University, 1510 Clifton Road, Atlanta, GA 30322, USA

* To whom correspondence should be addressed.
Ichiro Matsumura, E-mail: imatsum{at}emory.edu


  Abstract

Natural selection generally produces specific and efficient enzymes. In contrast, directed evolution experiments usually produce enzyme variants with broadened substrate specificity or enhanced catalytic promiscuity. Some proteins may be more evolvable than others, but few workers consider this problem when choosing starting points for laboratory evolution. Here, we review the variables associated with enzyme evolvability, namely promiscuity and mutational robustness. We present a qualitative model of adaptive evolution and recommend that protein engineers exploit their knowledge of natural history to identify evolvable wild-type proteins. Three examples of ‘generalist’ proteins that evolved in the laboratory into ‘specialists’ are described to illustrate the practical utility of this point.

Keywords: adaptive evolution; catalytic promiscuity; directed evolution; evolvability; robustness.
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