Celniker SE, Wheeler DA, Kronmiller B, Carlson JW, Halpern A, Patel S,
Adams M, Champe M, Dugan SP, Frise E, Hodgson A, George RA,
Hoskins RA, Laverty T, Muzny DM, Nelson CR, Pacleb JM, Park S,
Pfeiffer BD, Richards S, Sodergren EJ, Svirskas R, Tabor PE, Wan K,
Stapleton M, Sutton GG, Venter C, Weinstock G, Scherer SE, Myers EW,
Gibbs RA, Rubin GM.
Finishing a whole-genome shotgun: release 3 of the Drosophila melanogaster
euchromatic genome sequence.
Genome Biol. 2002;3(12):RESEARCH0079. Epub 2002 Dec 23.
BACKGROUND: The Drosophila melanogaster genome was the first metazoan genome to
have been sequenced by the whole-genome shotgun (WGS) method. Two issues relating
to this achievement were widely debated in the genomics community: how correct is
the sequence with respect to base-pair (bp) accuracy and frequency of assembly
errors? And, how difficult is it to bring a WGS sequence to the accepted standard
for finished sequence? We are now in a position to answer these questions.
RESULTS: Our finishing process was designed to close gaps, improve sequence
quality and validate the assembly. Sequence traces derived from the WGS and draft
sequencing of individual bacterial artificial chromosomes (BACs) were assembled
into BAC-sized segments. These segments were brought to high quality, and then
joined to constitute the sequence of each chromosome arm. Overall assembly was
verified by comparison to a physical map of fingerprinted BAC clones. In the
current version of the 116.9 Mb euchromatic genome, called Release 3, the six
euchromatic chromosome arms are represented by 13 scaffolds with a total of 37
sequence gaps. We compared Release 3 to Release 2; in autosomal regions of unique
sequence, the error rate of Release 2 was one in 20,000 bp. CONCLUSIONS: The WGS
strategy can efficiently produce a high-quality sequence of a metazoan genome
while generating the reagents required for sequence finishing. However, the
initial method of repeat assembly was flawed. The sequence we report here,
Release 3, is a reliable resource for molecular genetic experimentation and
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