Finishing a whole-genome shotgun: release 3 of the Drosophila melanogaster euchromatic genome sequence.
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 computational analysis.
Celniker
Susan E
SE
Berkeley Drosophila Genome Project, Department of Genome Sciences, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. celniker@bdgp.lbl.gov
Wheeler
David A
DA
Kronmiller
Brent
B
Carlson
Joseph W
JW
Halpern
Aaron
A
Patel
Sandeep
S
Adams
Mark
M
Champe
Mark
M
Dugan
Shannon P
SP
Frise
Erwin
E
Hodgson
Ann
A
George
Reed A
RA
Hoskins
Roger A
RA
Laverty
Todd
T
Muzny
Donna M
DM
Nelson
Catherine R
CR
Pacleb
Joanne M
JM
Park
Soo
S
Pfeiffer
Barret D
BD
Richards
Stephen
S
Sodergren
Erica J
EJ
Svirskas
Robert
R
Tabor
Paul E
PE
Wan
Kenneth
K
Stapleton
Mark
M
Sutton
Granger G
GG
Venter
Craig
C
Weinstock
George
G
Scherer
Steven E
SE
Myers
Eugene W
EW
Gibbs
Richard A
RA
Rubin
Gerald M
GM
D000818:Animals; D004331:Drosophila melanogaster / Q000235:genetics*; D022041:Euchromatin / Q000235:genetics*; D016678:Genome; D020161:Physical Chromosome Mapping / Q000379:methods; D012107:Research Design; D017422:Sequence Analysis, DNA / Q000379:methods*; D014960:X Chromosome / Q000235:genetics
D022041:Euchromatin