Big Genomes Facilitate the Comparative Identification of Regulatory Elements Export

@article{citeulike:4133229, abstract = {<p>The identification of regulatory sequences in animal genomes remains a significant challenge. Comparative genomic methods that use patterns of evolutionary conservation to identify non-coding sequences with regulatory function have yielded many new vertebrate enhancers. However, these methods have not contributed significantly to the identification of regulatory sequences in sequenced invertebrate taxa. We demonstrate here that this differential success, which is often attributed to fundamental differences in the nature of vertebrate and invertebrate regulatory sequences, is instead primarily a product of the relatively small size of sequenced invertebrate genomes. We sequenced and compared loci involved in early embryonic patterning from four species of true fruit flies (family Tephritidae) that have genomes four to six times larger than those of <italic>Drosophila melanogaster</italic>. Unlike in <italic>Drosophila</italic>, where virtually all non-coding DNA is highly conserved, blocks of conserved non-coding sequence in tephritids are flanked by large stretches of poorly conserved sequence, similar to what is observed in vertebrate genomes. We tested the activities of nine conserved non-coding sequences flanking the <italic>even-skipped</italic> gene of the teprhitid <italic>Ceratis capitata</italic> in transgenic <italic>D. melanogaster</italic> embryos, six of which drove patterns that recapitulate those of known <italic>D. melanogaster</italic> enhancers. In contrast, none of the three non-conserved tephritid non-coding sequences that we tested drove expression in <italic>D. melanogaster</italic> embryos. Based on the landscape of non-coding conservation in tephritids, and our initial success in using conservation in tephritids to identify <italic>D. melanogaster</italic> regulatory sequences, we suggest that comparison of tephritid genomes may provide a systematic means to annotate the non-coding portion of the <italic>D. melanogaster</italic> genome. We also propose that large genomes be given more consideration in the selection of species for comparative genomics projects, to provide increased power to detect functional non-coding DNAs and to provide a less biased view of the evolution and function of animal genomes.</p>}, author = {Peterson, Brant K. and Hare, Emily E. and Iyer, Venky N. and Storage, Steven and Conner, Laura and Papaj, Daniel R. and Kurashima, Rick and Jang, Eric and Eisen, Michael B.}, citeulike-article-id = {4133229}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pone.0004688}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19259274}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19259274}, day = {4}, doi = {10.1371/journal.pone.0004688}, journal = {PLoS ONE}, keywords = {cns-differences, conservation, cross-species-enhancer, inter-cns-distances}, month = {March}, number = {3}, pages = {e4688+}, posted-at = {2009-03-10 13:55:36}, priority = {2}, publisher = {Public Library of Science}, title = {Big Genomes Facilitate the Comparative Identification of Regulatory Elements}, url = {http://dx.doi.org/10.1371/journal.pone.0004688}, volume = {4}, year = {2009} }

TY - JOUR ID - citeulike:4133229 L3 - citeulike-article-id:4133229 N2 - <p>The identification of regulatory sequences in animal genomes remains a significant challenge. Comparative genomic methods that use patterns of evolutionary conservation to identify non-coding sequences with regulatory function have yielded many new vertebrate enhancers. However, these methods have not contributed significantly to the identification of regulatory sequences in sequenced invertebrate taxa. We demonstrate here that this differential success, which is often attributed to fundamental differences in the nature of vertebrate and invertebrate regulatory sequences, is instead primarily a product of the relatively small size of sequenced invertebrate genomes. We sequenced and compared loci involved in early embryonic patterning from four species of true fruit flies (family Tephritidae) that have genomes four to six times larger than those of <italic>Drosophila melanogaster</italic>. Unlike in <italic>Drosophila</italic>, where virtually all non-coding DNA is highly conserved, blocks of conserved non-coding sequence in tephritids are flanked by large stretches of poorly conserved sequence, similar to what is observed in vertebrate genomes. We tested the activities of nine conserved non-coding sequences flanking the <italic>even-skipped</italic> gene of the teprhitid <italic>Ceratis capitata</italic> in transgenic <italic>D. melanogaster</italic> embryos, six of which drove patterns that recapitulate those of known <italic>D. melanogaster</italic> enhancers. In contrast, none of the three non-conserved tephritid non-coding sequences that we tested drove expression in <italic>D. melanogaster</italic> embryos. Based on the landscape of non-coding conservation in tephritids, and our initial success in using conservation in tephritids to identify <italic>D. melanogaster</italic> regulatory sequences, we suggest that comparison of tephritid genomes may provide a systematic means to annotate the non-coding portion of the <italic>D. melanogaster</italic> genome. We also propose that large genomes be given more consideration in the selection of species for comparative genomics projects, to provide increased power to detect functional non-coding DNAs and to provide a less biased view of the evolution and function of animal genomes.</p> IS - 3 JF - PLoS ONE TI - Big Genomes Facilitate the Comparative Identification of Regulatory Elements PB - Public Library of Science VL - 4 SP - e4688 KW - cns-differences KW - conservation KW - cross-species-enhancer KW - inter-cns-distances AU - Peterson, Brant AU - Hare, Emily AU - Iyer, Venky AU - Storage, Steven AU - Conner, Laura AU - Papaj, Daniel AU - Kurashima, Rick AU - Jang, Eric AU - Eisen, Michael PY - 2009/03/04/ UR - http://dx.doi.org/10.1371/journal.pone.0004688 ER -