Y east Genome

Detection of Frame-Shift Error in theSequences

Naoko Kasahara

kasahara@crl.hitachi.co.jp

Naoyuki Haradan-harada@crl.hitachi.co.jp

Keiichi Nagai

k-nagai@crl.hitachi.co.jp

Central Research Laboratory, Hitachi, Ltd.
1-280 Higashi-koigakubo, Kokubunji-shi, Tokyo 185-8601, Japan

1 Introduction
Recently the number of organisms, whose whole genome sequences have been determined, is increasing.
They are utilized to various analyses, such as comparative genomics. In case of protein sequence
analyses, frame-shift errors are crucial. Even in the 99.99 % accuracy, there might be about 1,000errors including insertions and deletions in the YEAST genome sequence. We have developed twokinds of homology search methods based on Smith-Waterman-like algorithm considering nucleotide
and amino acid gaps simultaneously. One compares a translated DNA sequence and a protein sequence(transq) [1]. The other compares two translated DNA sequences (transw) [2]. We also developed theirparallel computation programs to realize practical computation time for database search [3]. We
utilized them to detect frame-shift errors in the YEAST genome sequence.

2 Method and Results
We obtained the YEAST genome sequence from SGD(http://genome-www.stanford.edu/Saccharomyces/, June, 1998). We tried to nd frame-shift errors
in the regions where short ORFs are located. We compared the sequences in those regions with theall amino acid sequences in SwissProt (rel. 34.0) using transq. An example of the results is shown inFig. 1. The alignment obtained by transw is also shown in Fig. 2. From the alignments with a YEAST
hypothetical protein including an intron, there might be two frame-shift errors in this region. As aresult, the originally assigned three ORFs [4] could be connected to one ORF as shown in Fig. 3. The
potential substitution errors are also shown in Fig. 1 and Fig. 2. We consider our methods is ecientto detect frame-shift errors as well as substitution errors in the genome sequences.

References[1] Kasahara, N., Hiraoka, S., and Nagai, K., Direct comparison between DNA and amino acid sequences based on a dynamic programming method, Genome Informatics 1996, Universal AcademyPress, 202{203, 1996.
[2] Irie, R., Kasahara, N., Hiraoka, S., and Nagai, K., Codon-sensitive comparison of DNA sequences
contains insertions/deletions and statistical signi cance of the similarity scores, Genome Informatics 1997, Universal Academy Press, 286{287, 1997.
[3] Kasahara, N., Hiraoka, S., Irie, R., and Nagai, K., Highly sensitive homology search methods onparallel computer, Genome Informatics 1997, Universal Academy Press, 294{295, 1997.
[4] Mewes, H.W., Albermann, K., Bahr, M., Frishman, D., Gkeissner, A., Hani, J., Heumann, K.,
Kleine, K., Maierl, A., Oliver, S.G., Pfei er, F., and Zollner, A., Overview of the yeast genome,Nature, 387:7{65, 1997.
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Query sequence:Yeast Chromosome VI ( posision 1500 )Target sequence:>sp:YH18_YEAST HYPOTHETICAL 68.9 KD PROTEIN IN PUR5 3'REGION.
Score: 6929 - strand
Alignment region Query :3709 .. 1802
Target:
1 .. 603

A
A
A A
A
A
AA

Query: 3469 tataatgagttgagttttccgtgtcctggaacgttgtcacgaaatagcgagtgccaggccg
TyrAsnGluLeuSer PheArgValLeuGluArgCysHisGluIleAlaSerAlaArgPro| | | | || | | | | | | : | | | | | | |Target: 81 TyrAsnGluLeuSer PheArgValLeuGluArgCysTyrGluIleAlaSerAlaArgPro

Query: 3408 aacgacagctctacgatgcgtactttcactgactttgtttctggcgcacctattgtaagg
AsnAspSerSerThrMetArgThrPheThrAspPheValSerGlyAlaProIleValArg| | | | | | | | | | | | | | | . | | | |Target: 102 AsnAspSerSerThrMetArgThrPheThrAspPheValSerGlyThrProIleValArg:detected frame-shift errors

Fig. 1:detected substitutions

Alignment result obtained by transqAAAA A
AAAAA
AA

Query sequence:Yeast Chromosome VI ( posision 1500 )Target sequence:>YSCH9117 Saccharomyces cerevisiae chromosome VIII cosmid 9177.
Query:3469 tataatgagttgagttttccgtgtcctggaacgttgtcacgaaatagcgagtgccaggccg
TyrAsnGluLeuSer PheArgValLeuGluArgCysHisGluIleAlaSerAlaArgPro| | | | || | | | | | | : | | | | | | |TyrAsnGluLeuSer PheArgValLeuGluArgCysTyrGluIleAlaSerAlaArgPro
Target:51705 tataatgagttgagt-ttccgtgtcctggaacgttgttacgaaatagcgagtgccaggccg
Query:3408 aacgacagctctacgatgcgtactttcactgactttgtttctggcgcacctattgtaagg
AsnAspSerSerThrMetArgThrPheThrAspPheValSerGlyAlaProIleValArg| | | | | | | | | | | | | | | . | | | |AsnAspSerSerThrMetArgThrPheThrAspPheValSerGlyThrProIleValArg
Target:51765 aacgacagctctacgatgcgtactttcactgactttgtttctggcacacctattgtaagg:detected frame-shift errors

Fig. 2:detected substitutions

Alignment result obtaind by transw

3000

2000

4000

Yeast Chromosome VI064

original ORFs

066

065

new ORF
sp:YH18_YEAST
Fig. 3Comparison original and new ORFs

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