Beyond the Identification of Transcribed Sequences: Functional and Expression Analysis

9th Annual Workshop, October 28-31, 1999

Co-sponsored by the U.S. Department of Energy


Functional and molecular evolutional analysis of predicted gene products of human long cDNAs

Reiko Kikuno, Takahiro Nagase, Ken-Ichi Ishikawa, Mikita Suyama, Mina Waki, Makoto Hirosawa, Nobuo Nomura, and Osamu Ohara

Kazusa DNA Research Institute
Kisarazu, Chiba, Japan

Our cDNA sequencing project has focused on human cDNAs that have a potential to code for large proteins expressed in brain and so far published more than 1200 new cDNA sequences. We have assigned a KIAA number to each sequence as a name of the gene. Among them, the gene products of 1117 cDNAs were predicted and studied in detail from functional and molecular evolutional viewpoints by computer analysis at amino acid sequence level. Database search of the protein sequences revealed that functions of 682 proteins (61.1%) were classified into 7 classes such as Structure/Motility (8.7%), Metabolism (3.2%), Cell division (1.1%), Signal/Communication (25.3 %), Nucleic acids managing (16.7%), Protein managing (4.1%), and others (1.9%), while the functions of 139 protein could not be predicted although the sequences indicated significant similarity to other sequences and/or motifs in public databases. The number of the protein sequences that showed no significant similarity neither to known sequences nor to motifs was 296 (26.5%).

The detail results of our analyses for each KIAA gene can be browsed in our HUGE protein database, which is accessible via World Wide Web at In addition, the HUGE database contains experimental results such as expression profiling and RH-mapping together with their experimental conditions. Functions of keyword search and homology search were also prepared to retrieve KIAA entries of user's interest.

To examine the evolutionary origin of KIAA genes, we compared the protein sequences with those deduced from the genomes of yeast (S. cerevisiae) and nematode (C. elegans). It was shown that 1) only 3% and 10% of KIAA genes had homologous genes (i.e., homologous along the entire coding regions) in yeast and nematode, respectively; 2) 35% and 14 % of KIAA gene products were lack of any homologous regions to gene products encoded by the genomes of yeast and nematode, respectively. The remaining KIAA gene products were found to have some homologous region(s) in these lower eukaryotes. Possible evolutionary processes of these genes will be also discussed.

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