Natalia Volfovsky ^{1, 2,  3}, Brian J. Haas ¹, and Steven L. Salzberg ¹

¹ The Institute for Genomic Research, Rockville, Maryland 20850, USA
² Present address: Advanced Biomedical Computing Center, National Cancer Institute-Frederick/SAIC,
Frederick, Maryland 21702, USA.
³ Corresponding author.
E-MAIL:    natalia@ncifcrf.gov     FAX: (301) 838-0208. 

Very short exons, also known as micro-exons, occur in large numbers in some eukaryotic genomes. Existing annotation tools have a limited ability to recognize these short sequences, which range in length up to 25 bp. Here, we describe a computational method for the identification of micro-exons using near-perfect alignments between cDNA and genomic DNA sequences. Using this method, we detected 319 micro-exons in 4 complete genomes, of which 224 were previously unknown, human (170), the nematode Caenorhabditis elegans (4), the fruit fly Drosophila melanogaster (14), and the mustard plant Arabidopsis thaliana (36). Comparison of our computational method with popular cDNA alignment programs shows that the new algorithm is both efficient and accurate. The algorithm also aids in the discovery of micro-exon-skipping events and cross-species micro-exon conservation.  [Supplementary material available online at http://www.genome.org ] 

1. Haas BJ, Volfovsky N, Town CD, Troukhan M, Alexandrov N, Feldmann KA, Flavell RB, White O, Salzberg SL. Full-length messenger RNA sequences greatly improve genome annotation. Genome Biol. 2002;3(6):RESEARCH0029. Epub 2002 May 30.

2. Volfovsky N, Haas BJ, Salzberg SL. A clustering method for repeat analysis in DNA sequences. Genome Biol. 2001;2(8):RESEARCH0027. Epub 2001 Aug 01.

3. Salzberg SL. Genomics: Yeast rises again. Nature. 2003 May 15;423(6937):233-4.

4. Fraser CM, Eisen JA, Nelson KE, Paulsen IT, Salzberg SL. The value of complete microbial genome sequencing (you get what you pay for). J Bacteriol. 2002 Dec;184(23):6403-5; discusion 6405. Review.

5. Saha S, Ansari AZ , Jarell KZ, and Ptashne M, "RNA Sequences that Work as Transcriptional Activating Regions".

6. Hovsepian JA, and Frenster JH, "RNA-Induced Melting of DNA during Selective Gene Transcription".

7. Frenster JH, "Ultrastructural Probes of Active DNA Sites, and the RNA Activators of DNA".