Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures.

Alexander Stark; Michael F Lin; Pouya Kheradpour; Jakob Skou Pedersen; Leopold Parts; Joseph W Carlson; Madeline A Crosby; Matthew D Rasmussen; Sushmita Roy; Ameya N Deoras; J Graham Ruby; Julius Brennecke; Harvard FlyBase curators; Berkeley Drosophila Genome Project; Emily Hodges; Angie S Hinrichs; Anat Caspi; Benedict Paten; Seung-Won Park; Mira V Han; Morgan L Maeder; Benjamin J Polansky; Bryanne E Robson; Stein Aerts; Jacques van Helden; Bassem Hassan; Donald G Gilbert; Deborah A Eastman; Michael Rice; Michael Weir; Matthew W Hahn; Yongkyu Park; Colin N Dewey; Lior Pachter; W James Kent; David Haussler; Eric C Lai; David P Bartel; Gregory J Hannon; Thomas C Kaufman; Michael B Eisen; Andrew G Clark; Douglas Smith; Susan E Celniker; William M Gelbart; Manolis Kellis

doi:10.1038/nature06340

Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures.

Alexander Stark, Michael F Lin, Pouya Kheradpour, Jakob Skou Pedersen, Leopold Parts, Joseph W Carlson, Madeline A Crosby, Matthew D Rasmussen, Sushmita Roy, Ameya N Deoras, J Graham Ruby, Julius Brennecke, Harvard FlyBase curators, Berkeley Drosophila Genome Project, Emily Hodges, Angie S Hinrichs, Anat Caspi, Benedict Paten, Seung-Won Park, Mira V HanMorgan L Maeder, Benjamin J Polansky, Bryanne E Robson, Stein Aerts, Jacques van Helden, Bassem Hassan, Donald G Gilbert, Deborah A Eastman, Michael Rice, Michael Weir, Matthew W Hahn, Yongkyu Park, Colin N Dewey, Lior Pachter, W James Kent, David Haussler, Eric C Lai, David P Bartel, Gregory J Hannon, Thomas C Kaufman, Michael B Eisen, Andrew G Clark, Douglas Smith, Susan E Celniker, William M Gelbart, Manolis Kellis

Functional Genomics

446 Citations (Scopus)

Abstract

Sequencing of multiple related species followed by comparative genomics analysis constitutes a powerful approach for the systematic understanding of any genome. Here, we use the genomes of 12 Drosophila species for the de novo discovery of functional elements in the fly. Each type of functional element shows characteristic patterns of change, or 'evolutionary signatures', dictated by its precise selective constraints. Such signatures enable recognition of new protein-coding genes and exons, spurious and incorrect gene annotations, and numerous unusual gene structures, including abundant stop-codon readthrough. Similarly, we predict non-protein-coding RNA genes and structures, and new microRNA (miRNA) genes. We provide evidence of miRNA processing and functionality from both hairpin arms and both DNA strands. We identify several classes of pre- and post-transcriptional regulatory motifs, and predict individual motif instances with high confidence. We also study how discovery power scales with the divergence and number of species compared, and we provide general guidelines for comparative studies.

Original language	English
Journal	Nature
Volume	450
Issue number	7167
Pages (from-to)	219-32
Number of pages	13
ISSN	0028-0836
DOIs	https://doi.org/10.1038/nature06340
Publication status	Published - 2007

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Stark, A., Lin, M. F., Kheradpour, P., Pedersen, J. S., Parts, L., Carlson, J. W., Crosby, M. A., Rasmussen, M. D., Roy, S., Deoras, A. N., Ruby, J. G., Brennecke, J., Harvard FlyBase curators, Berkeley Drosophila Genome Project, Hodges, E., Hinrichs, A. S., Caspi, A., Paten, B., Park, S-W., ... Kellis, M. (2007). Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures. Nature, 450(7167), 219-32. https://doi.org/10.1038/nature06340

Stark, A, Lin, MF, Kheradpour, P, Pedersen, JS, Parts, L, Carlson, JW, Crosby, MA, Rasmussen, MD, Roy, S, Deoras, AN, Ruby, JG, Brennecke, J, Harvard FlyBase curators, Berkeley Drosophila Genome Project, Hodges, E, Hinrichs, AS, Caspi, A, Paten, B, Park, S-W, Han, MV, Maeder, ML, Polansky, BJ, Robson, BE, Aerts, S, van Helden, J, Hassan, B, Gilbert, DG, Eastman, DA, Rice, M, Weir, M, Hahn, MW, Park, Y, Dewey, CN, Pachter, L, Kent, WJ, Haussler, D, Lai, EC, Bartel, DP, Hannon, GJ, Kaufman, TC, Eisen, MB, Clark, AG, Smith, D, Celniker, SE, Gelbart, WM & Kellis, M 2007, 'Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures.', Nature, vol. 450, no. 7167, pp. 219-32. https://doi.org/10.1038/nature06340

@article{c33ffb404dc111dd8d9f000ea68e967b,

title = "Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures.",

abstract = "Sequencing of multiple related species followed by comparative genomics analysis constitutes a powerful approach for the systematic understanding of any genome. Here, we use the genomes of 12 Drosophila species for the de novo discovery of functional elements in the fly. Each type of functional element shows characteristic patterns of change, or 'evolutionary signatures', dictated by its precise selective constraints. Such signatures enable recognition of new protein-coding genes and exons, spurious and incorrect gene annotations, and numerous unusual gene structures, including abundant stop-codon readthrough. Similarly, we predict non-protein-coding RNA genes and structures, and new microRNA (miRNA) genes. We provide evidence of miRNA processing and functionality from both hairpin arms and both DNA strands. We identify several classes of pre- and post-transcriptional regulatory motifs, and predict individual motif instances with high confidence. We also study how discovery power scales with the divergence and number of species compared, and we provide general guidelines for comparative studies.",

author = "Alexander Stark and Lin, {Michael F} and Pouya Kheradpour and Pedersen, {Jakob Skou} and Leopold Parts and Carlson, {Joseph W} and Crosby, {Madeline A} and Rasmussen, {Matthew D} and Sushmita Roy and Deoras, {Ameya N} and Ruby, {J Graham} and Julius Brennecke and {Harvard FlyBase curators} and {Berkeley Drosophila Genome Project} and Emily Hodges and Hinrichs, {Angie S} and Anat Caspi and Benedict Paten and Seung-Won Park and Han, {Mira V} and Maeder, {Morgan L} and Polansky, {Benjamin J} and Robson, {Bryanne E} and Stein Aerts and {van Helden}, Jacques and Bassem Hassan and Gilbert, {Donald G} and Eastman, {Deborah A} and Michael Rice and Michael Weir and Hahn, {Matthew W} and Yongkyu Park and Dewey, {Colin N} and Lior Pachter and Kent, {W James} and David Haussler and Lai, {Eric C} and Bartel, {David P} and Hannon, {Gregory J} and Kaufman, {Thomas C} and Eisen, {Michael B} and Clark, {Andrew G} and Douglas Smith and Celniker, {Susan E} and Gelbart, {William M} and Manolis Kellis",

note = "Keywords: Animals; Base Sequence; Binding Sites; Conserved Sequence; Drosophila; Drosophila Proteins; Evolution, Molecular; Exons; Gene Expression Regulation; Genes, Insect; Genome, Insect; Genomics; MicroRNAs; Molecular Sequence Data; Organ Specificity; Phylogeny; Untranslated Regions",

year = "2007",

doi = "10.1038/nature06340",

language = "English",

volume = "450",

pages = "219--32",

journal = "Nature",

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T1 - Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures.

AU - Stark, Alexander

AU - Lin, Michael F

AU - Kheradpour, Pouya

AU - Pedersen, Jakob Skou

AU - Parts, Leopold

AU - Carlson, Joseph W

AU - Crosby, Madeline A

AU - Rasmussen, Matthew D

AU - Roy, Sushmita

AU - Deoras, Ameya N

AU - Ruby, J Graham

AU - Brennecke, Julius

AU - Harvard FlyBase curators

AU - Berkeley Drosophila Genome Project

AU - Hodges, Emily

AU - Hinrichs, Angie S

AU - Caspi, Anat

AU - Paten, Benedict

AU - Park, Seung-Won

AU - Han, Mira V

AU - Maeder, Morgan L

AU - Polansky, Benjamin J

AU - Robson, Bryanne E

AU - Aerts, Stein

AU - van Helden, Jacques

AU - Hassan, Bassem

AU - Gilbert, Donald G

AU - Eastman, Deborah A

AU - Rice, Michael

AU - Weir, Michael

AU - Hahn, Matthew W

AU - Park, Yongkyu

AU - Dewey, Colin N

AU - Pachter, Lior

AU - Kent, W James

AU - Haussler, David

AU - Lai, Eric C

AU - Bartel, David P

AU - Hannon, Gregory J

AU - Kaufman, Thomas C

AU - Eisen, Michael B

AU - Clark, Andrew G

AU - Smith, Douglas

AU - Celniker, Susan E

AU - Gelbart, William M

AU - Kellis, Manolis

N1 - Keywords: Animals; Base Sequence; Binding Sites; Conserved Sequence; Drosophila; Drosophila Proteins; Evolution, Molecular; Exons; Gene Expression Regulation; Genes, Insect; Genome, Insect; Genomics; MicroRNAs; Molecular Sequence Data; Organ Specificity; Phylogeny; Untranslated Regions

PY - 2007

Y1 - 2007

N2 - Sequencing of multiple related species followed by comparative genomics analysis constitutes a powerful approach for the systematic understanding of any genome. Here, we use the genomes of 12 Drosophila species for the de novo discovery of functional elements in the fly. Each type of functional element shows characteristic patterns of change, or 'evolutionary signatures', dictated by its precise selective constraints. Such signatures enable recognition of new protein-coding genes and exons, spurious and incorrect gene annotations, and numerous unusual gene structures, including abundant stop-codon readthrough. Similarly, we predict non-protein-coding RNA genes and structures, and new microRNA (miRNA) genes. We provide evidence of miRNA processing and functionality from both hairpin arms and both DNA strands. We identify several classes of pre- and post-transcriptional regulatory motifs, and predict individual motif instances with high confidence. We also study how discovery power scales with the divergence and number of species compared, and we provide general guidelines for comparative studies.

AB - Sequencing of multiple related species followed by comparative genomics analysis constitutes a powerful approach for the systematic understanding of any genome. Here, we use the genomes of 12 Drosophila species for the de novo discovery of functional elements in the fly. Each type of functional element shows characteristic patterns of change, or 'evolutionary signatures', dictated by its precise selective constraints. Such signatures enable recognition of new protein-coding genes and exons, spurious and incorrect gene annotations, and numerous unusual gene structures, including abundant stop-codon readthrough. Similarly, we predict non-protein-coding RNA genes and structures, and new microRNA (miRNA) genes. We provide evidence of miRNA processing and functionality from both hairpin arms and both DNA strands. We identify several classes of pre- and post-transcriptional regulatory motifs, and predict individual motif instances with high confidence. We also study how discovery power scales with the divergence and number of species compared, and we provide general guidelines for comparative studies.

U2 - 10.1038/nature06340

DO - 10.1038/nature06340

M3 - Journal article

C2 - 17994088

SN - 0028-0836

VL - 450

SP - 219

EP - 232

JO - Nature

JF - Nature

IS - 7167

ER -

Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures.

Abstract

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