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Proc Natl Acad Sci U S A. 2004 Nov 30;101(48):16745-9. Epub 2004 Nov 19.

Evolution of new nonantibody proteins via iterative somatic hypermutation.

Author information

1
Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093-0647, USA.

Abstract

B lymphocytes use somatic hypermutation (SHM) to optimize immunoglobulins. Although SHM can rescue single point mutations deliberately introduced into nonimmunoglobulin genes, such experiments do not show whether SHM can efficiently evolve challenging novel phenotypes requiring multiple unforeseeable mutations in nonantibody proteins. We have now iterated SHM over 23 rounds of fluorescence-activated cell sorting to create monomeric red fluorescent proteins with increased photostability and far-red emissions (e.g., 649 nm), surpassing the best efforts of structure-based design. SHM offers a strategy to evolve nonantibody proteins with desirable properties for which a high-throughput selection or viable single-cell screen can be devised.

PMID:
15556995
PMCID:
PMC529417
DOI:
10.1073/pnas.0407752101
[Indexed for MEDLINE]
Free PMC Article

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