Comparison of intron-containing and intron-lacking human genes elucidates putative exonic splicing enhancers.
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.
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA. afedorov@nucleus.harvard.edu
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Fedorov
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Saxonov
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Fedorova
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Daizadeh
D017398:Alternative Splicing; D001482:Base Composition; D016208:Databases, Factual; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005796:Genes / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics*; D016366:Open Reading Frames; D011506:Proteins / Q000235:genetics; D013223:Statistics as Topic
D011506:Proteins