The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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Published online 13 January 2003 doi:10.1084/jem.20020250
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© Rockefeller University Press, 0022-1007/2003/1/207 $5.00
The Journal of Experimental Medicine, Volume 197, Number 2, 207-220

Prospective Estimation of Recombination Signal Efficiency and Identification of Functional Cryptic Signals in the Genome by Statistical Modeling

Lindsay G. Cowell1, Marco Davila1, Kaiyong Yang1, Thomas B. Kepler2 and Garnett Kelsoe1

1 Department of Immunology, Center for Bioinformatics and Computational Biology, Duke University Medical Center, Durham, NC 27710
2 Department of Biostatistics and Bioinformatics, Center for Bioinformatics and Computational Biology, Duke University Medical Center, Durham, NC 27710

Address correspondence to G. Kelsoe, Department of Immunology, DUMC 3010, Duke University Medical Center, Durham, NC 27710. Phone: 919-613-7815; Fax: 919-613-7878; E-mail: ghkelsoe{at}duke.edu

The recombination signals (RS) that guide V(D)J recombination are phylogenetically conserved but retain a surprising degree of sequence variability, especially in the nonamer and spacer. To characterize RS variability, we computed the position-wise information, a measure correlated with sequence conservation, for each nucleotide position in an RS alignment and demonstrate that most position-wise information is present in the RS heptamers and nonamers. We have previously demonstrated significant correlations between RS positions and here show that statistical models of the correlation structure that underlies RS variability efficiently identify physiologic and cryptic RS and accurately predict the recombination efficiencies of natural and synthetic RS. In scans of mouse and human genomes, these models identify a highly conserved family of repetitive DNA as an unexpected source of frequent, cryptic RS that rearrange both in extrachromosomal substrates and in their genomic context.

Key Words: recombination signal sequence • cryptic recombination signal • recombination efficiency • recombination signal models • illegitimate V(D)J recombination


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