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Infection and Immunity, September 1998, p. 4305-4312, Vol. 66, No. 9
Sidney Kimmel Cancer Center, San Diego,
California 92121,1 and
Genome Sequencing
Center, Washington University School of Medicine, St. Louis,
Missouri 631082
Received 12 December 1997/Returned for modification 24 March
1998/Accepted 4 June 1998
Raw sequence data representing the majority of a bacterial genome
can be obtained at a tiny fraction of the cost of a completed sequence.
To demonstrate the utility of such a resource, 870 single-stranded M13
clones were sequenced from a shotgun library of the Salmonella typhi Ty2 genome. The sequence reads averaged over 400 bases and sampled the genome with an average spacing of once every 5,000 bases. A
total of 339,243 bases of unique sequence was generated (approximately
7% representation). The sample of 870 sequences was compared to
the complete Escherichia coli K-12 genome and to the rest
of the GenBank database, which can also be considered a collection of
sampled sequences. Despite the incomplete S. typhi data set, interesting categories could easily be discerned. Sixteen percent of the sequences determined from S. typhi had
close homologs among known Salmonella sequences
(P < 1e
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Comparison of Sample Sequences of the Salmonella typhi
Genome to the Sequence of the Complete Escherichia coli
K-12 Genome
40 in BlastX or
BlastN), reflecting the proportion of these genomes that have been
sequenced previously; 277 sequences (32%) had no apparent orthologs in
the complete E. coli K-12 genome (P > 1e
20), of which 155 sequences (18%) had no
close similarities to any sequence in the database (P > 1e
5). Eight of the 277 sequences had
similarities to genes in other strains of E. coli or
plasmids, and six sequences showed evidence of novel phage lysogens or
sequence remnants of phage integrations, including a member of the
lambda family (P < 1e
15).
Twenty-three sample sequences had a significantly closer similarity a
sequence in the database from organisms other than the E. coli/Salmonella clade (which includes Shigella and
Citrobacter). These sequences are new candidate lateral
transfer events to the S. typhi lineage or deletions
on the E. coli K-12 lineage. Eleven putative junctions of
insertion/deletion events greater than 100 bp were observed in the
sample, indicating that well over 150 such events may distinguish S. typhi from E. coli K-12. The need for
automatic methods to more effectively exploit sample sequences is
discussed.
*
Corresponding author. Mailing address: Sidney Kimmel
Cancer Center, 10835 Altman Row, San Diego, CA 92121. Phone: (619)
450-5990, ext. 280. Fax: (619) 550-3998. E-mail:
mmcclelland{at}skcc.org.
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