Assessing the Drosophila melanogaster and Anopheles gambiae Genome Annotations Using

Genome-Wide Sequence Comparisons

Jaillon O, Dossat C, Eckenberg R, Eiglmeier K, Segurens B, Aury J, Roth CW, Scarpelli C, Brey PT, Weissenbach J, Wincker P

Genoscope/Centre National de SequencageUnite de Biochimie et Biologie Moleculaire des Insectes, Institut Pasteur

Genome Res. (2003) 13:1595-99

Scott Zuyderduyn 05 Feb 2004

MEDG505

Genome Sequences

Anopheles gambiae“Malaria Mosquito”

Sequenced by Celera Genomics (Holt RA et al., 2002)

BA

CK

GR

OU

ND

Drosophila melanogaster“Fruit Fly”

Sequenced by Celera Genomics (Myers EW et al.,

2000)

Genome Comparisons

1. EnsEMBL (http://www.ensembl.org)2. Zdobnov EM et al. (2002) Science 298:149-159.

Drosophila Anopheles

Genome Size (Mb)1 ~130 ~280

Karyotype1 2L,2R,3L,3R,4,X 2L,2R,3L,3R,X

Avg. Protein Length (bp)2 649 548

Avg. Intron Size (bp)2 628 1061

Avg. Coding Exon Size (bp)2 443 366

Avg. Introns / Gene2 4.67 3.47

Species Divergence2 250 million years(human-mouse ~ 100 million years)

BA

CK

GR

OU

ND

ExofishEXOn FInding by Sequence Homology

RE

SU

LTS

(+)

(-)

Ecores

(+)

(-)

Ecores

BDGP release 2

BDGP release 3

Ecores in DrosophilaR

ES

ULT

S

RE

SU

LTS

New Annotations

(+)

(-)

Ecores

cDNA

EnsEMBL Anopheles gene predictions

RE

SU

LTS

Annotating Anopheles with Drosophila

(+)

Ecores

cDNA

EnsEMBL Anopheles gene prediction

homolog of Innexin-7

RE

SU

LTS

Refining Annotations

(+)

Ecores

cDNA

EnsEMBL Anopheles gene prediction

homolog of tetraspanin family member

Ecores in AnophelesR

ES

ULT

S

Themeso An annotated genome can be used to start annotation of a new

genome

o An existing genome can be used to assess the annotation/assembly progress of a new genome

o A new genome can be used to refine annotations of the existing genome

CO

NC

LUS

ION

S

Questions

o How evolutionarily distant do two organisms have to be in order for their genomes to be effective in annotating coding regions? regulatory elements?

o Are there alternatives to sequence-based (primary structure) comparisons?

o Comparative genomic approaches make inferences from common elements. What about novel elements?

o In comparative genomics, the more genomes the better: what types of knowledge are gained as we include more genomes?

CO

NC

LUS

ION

S

Comparative Genomics

Zdobnov EM et al. (2002) Science 298:149-159.

BA

CK

GR

OU

ND

Fly-Mosquito Comparative GenomicsB

AC

KG

RO

UN

D

Exofish

o Used the well-characterized Drosophila ADH region and a set of Anopheles shotgun sequence reads to optimize TBLASTX parameters

RE

SU

LTS

EXOn FInding by Sequence Homology

RE

SU

LTS

Comparative Genoscope (http://www.genoscope.cns.fr/comparative)