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Nucleic Acids Research, 2001, Vol. 29, No. 7 1464-1469
© 2001 Oxford University Press

Comparison of intron-containing and intron-lacking human genes elucidates putative exonic splicing enhancers

Alexei Fedorov*, Serge Saxonov, Larisa Fedorova1 and Iraj Daizadeh

Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA and 1Department of Ophthalmology, New England Medical Center, Boston, MA 02111, USA

Of the rules used by the splicing machinery to precisely determine intron–exon boundaries only a fraction is known. Recent evidence suggests that specific short sequences within exons help in defining these boundaries. Such sequences are known as exonic splicing enhancers (ESE). A possible bioinformatical approach to studying ESE sequences is to compare genes that harbor introns with genes that do not. For this purpose two non-redundant samples of 719 intron-containing and 63 intron-lacking human genes were created. We performed a statistical analysis on these datasets of intron-containing and intron-lacking human coding sequences and found a statistically significant difference (P = 0.01) between these samples in terms of 5–6mer oligonucleotide distributions. The difference is not created by a few strong signals present in the majority of exons, but rather by the accumulation of multiple weak signals through small variations in codon frequencies, codon biases and context-dependent codon biases between the samples. A list of putative novel human splicing regulation sequences has been elucidated by our analysis.

* To whom correspondence should be addressed. Tel: +1 617 495 0560; Fax: +1 617 496 4313; Email: afedorov{at}nucleus.harvard.edu Present addresses: Serge Saxonov, Stanford Medical Informatics, 251 Campus Drive, Medical School Office Building X-215, Stanford, CA 94305, USA Iraj Daizadeh, Silicon Life Science, 1401 Camino del Mar, Suite #202, Del Mar, CA 92014, USA


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