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114. Identifying context-specific gene profiles of social, reproductive, and mate preference behavior in a fish species with female mate choice.

Author

Ramsey, Mary E., Maginnis, Tara L., Wong, Ryan Y., Brock, Chad, Cummings, Molly E., Clayton, David F., Konopka, Genevieve, and Ka Wan Li

Subjects
FISH speciation, SENSORY evaluation, STATHMIN, TYROSINE hydroxylase, SOCIAL control
Abstract

Sensory and social inputs interact with underlying gene suites to coordinate social behavior. Here we use a naturally complex system in sexual selection studies, the swordtail, to explore how genes associated with mate preference, receptivity, and social affiliation interact in the female brain under specific social conditions. We focused on 11 genes associated with mate preference in this species (neuroserpin, neuroligin-3, NMDA receptor, tPA, stathmin-2, β-1 adrenergic receptor) or with female sociosexual behaviors in other taxa (vasotocin, isotocin, brain aromatase, α-1 adrenergic receptor, tyrosine hydroxylase). We exposed females to four social conditions, including pairings of differing mate choice complexity (large males, large/small males, small males), and a social control (two females). Female mate preference differed significantly by context. Multiple discriminant analysis (MDA) of behaviors revealed a primary axis (explaining 50.2% between-group variance) highlighting differences between groups eliciting high preference behaviors (LL, LS) vs. other contexts, and a secondary axis capturing general measures distinguishing a non-favored group (SS) from other groups. Gene expression MDA revealed a major axis (68.4% between-group variance) that distinguished amongst differential male pairings and was driven by suites of "preference and receptivity genes"; whereas a second axis, distinguishing high affiliation groups (large males, females) from low (small males), was characterized by traditional affiliative-associated genes (isotocin, vasotocin). We found context-specific correlations between behavior and gene MDA, suggesting gene suites covary with behaviors in a socially relevant context. Distinct associations between "affiliative" and "preference" axes suggest mate preference may be mediated by distinct clusters from those of social affiliation. Our results highlight the need to incorporate natural complexity of mating systems into behavioral genomics. [ABSTRACT FROM AUTHOR]

Published
2012
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115. The zebra finch neuropeptidome: prediction,detection and expression.

Author

Fang Xie, London, Sarah E., Southey, Bruce R., Annangudi, Suresh P., Amare, Andinet, Rodriguez-Zas, Sandra L., Clayton, David F., and Sweedler, Jonathan V.

Subjects
ZEBRA finch, NEURAL transmission, NEUROPEPTIDES, PEPTIDE hormones, BIOINFORMATICS, LEARNING
Abstract

Background: Among songbirds, the zebra finch (Taeniopygia guttata) is an excellent model system for investigating the neural mechanisms underlying complex behaviours such as vocal communication, learning and social interactions. Neuropeptides and peptide hormones are cell-to-cell signalling molecules known to mediate similar behaviours in other animals. However, in the zebra finch, this information is limited. With the newly-released zebra finch genome as a foundation, we combined bioinformatics, mass-spectrometry (MS)-enabled peptidomics and molecular techniques to identify the complete suite of neuropeptide prohormones and final peptide products and their distributions. Results: Complementary bioinformatic resources were integrated to survey the zebra finch genome, identifying 70 putative prohormones. Ninety peptides derived from 24 predicted prohormones were characterized using several MS platforms; tandem MS confirmed a majority of the sequences. Most of the peptides described here were not known in the zebra finch or other avian species, although homologous prohormones exist in the chicken genome. Among the zebra finch peptides discovered were several unique vasoactive intestinal and adenylate cyclase activating polypeptide 1 peptides created by cleavage at sites previously unreported in mammalian prohormones. MS-based profiling of brain areas required for singing detected 13 peptides within one brain nucleus, HVC; in situ hybridization detected 13 of the 15 prohormone genes examined within at least one major song control nucleus. Expression mapping also identified prohormone messenger RNAs in areas associated with spatial learning and social behaviours. Based on the whole-genome analysis, 40 prohormone probes were found on a commonly used zebra finch brain microarray. Analysis of these newly annotated transcripts revealed that six prohormone probes showed altered expression after birds heard song playbacks in a paradigm of song recognition learning; we partially verify this result experimentally. Conclusions: The zebra finch peptidome and prohormone complement is now characterized. Based on previous microarray results on zebra finch vocal learning and synaptic plasticity, a number of these prohormones show significant changes during learning. Interestingly, most mammalian prohormones have counterparts in the zebra finch, demonstrating that this songbird uses similar biochemical pathways for neurotransmission and hormonal regulation. These findings enhance investigation into neuropeptide-mediated mechanisms of brain function, learning and behaviour in this model. [ABSTRACT FROM AUTHOR]

Published
2010
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116. A microarray for large-scale genomic and transcriptional analyses of the zebra finch ( Taeniopygia guttata) and other passerines.

Author

Naurin, Sara, Bensch, Staffan, Hansson, Bengt, Johansson, Tomas, Clayton, David F., Albrekt, Ann-Sofie, Von Schantz, Torbjörn, and Hasselquist, Dennis

Subjects
ZEBRA finch, POEPHILA, PASSERIFORMES, GENE expression, BIOLOGICAL research, GREATER whitethroat
Abstract

The microarray technology has revolutionized biological research in the last decade. By monitoring the expression of many genes simultaneously, microarrays can elucidate gene function, as well as scan entire genomes for candidate genes encoding complex traits. However, because of high costs of sequencing and design, microarrays have largely been restricted to a few model species. Cross-species microarray (CSM) analyses, where microarrays are used for other species than the one they were designed for, have had varied success. We have conducted a CSM analysis by hybridizing genomic DNA from the common whitethroat ( Sylvia communis) on a newly developed Affymetrix array designed for the zebra finch ( Taeniopygia guttata), the Lund-zf array. The results indicate a very high potential for the zebra finch array to act as a CSM utility in other passerine birds. When hybridizing zebra finch genomic DNA, 98% of the gene representatives had higher signal intensities than the background cut-off, and for the common whitethroat, we found the equivalent proportion to be as high as 96%. This was surprising given the fact that finches and warblers diverged 25–50 million years ago, but may be explained by a relatively low sequence divergence between passerines (89–93%). Passerine birds are widely used in studies of ecology and evolution, and a zebra finch array that can be used for many species may have a large impact on future research directions. [ABSTRACT FROM AUTHOR]

Published
2008
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118. Activation and Habituation of Extracellular Signal-Regulated Kinase Phosphorylation in Zebra Finch Auditory Forebrain during Song Presentation.

Author

Hui-Yun Cheng and Clayton, David F.

Subjects
*ZEBRA finch, *PROSENCEPHALON, *AUDITORY pathways, *GENES, *BIRDSONGS
Abstract

The sound of tape-recorded birdsong triggers a set of behavioral and physiological responses in zebra finches, including transcriptional activation of the zenk gene in the auditory forebrain. Song repetition leads to the stimulus-specific habituation of these responses. To gain insight into the mechanisms that couple auditory experience to gene regulation, we monitored the phosphorylation of the zebra finch extracellular signal-regulated kinase (ERK) protein by immunoblotting. Initial presentations of novel song (but not tones or noise) resulted in a rapid increase in ERK phosphorylation, followed by a return to basal levels within 5 min. This response was localized to the auditory forebrain where the zenk gene is activated. Sustained repetition of one song caused a selective habituation of the ERK response: a different song triggered another cycle of ERK phosphorylation without altering the habituated response to the first. To test directly for a role of ERK in experience-dependent zenk gene regulation, we infused an inhibitor of mitogen-activated and extracelular-regulated protein kinase kinase (MEK-1; the enzyme responsible for ERK activation) unilaterally into one auditory lobule just before song stimulation. The song-induced increase in zenk mRNA was blocked on the side of the injection, but not on the contralateral (uninfused) side. These results show that ERK phosphorylation is necessary for the initiation of the zenk gene response to novel song and identify ERK as a plausible site of signal integration underlying the selective habituation of genomic responses to a repeated song. [ABSTRACT FROM AUTHOR]

Published
2004
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120. Towards complete and error-free genome assemblies of all vertebrate species

Author

Rhie, Arang, McCarthy, Shane A, Fedrigo, Olivier, Damas, Joana, Formenti, Giulio, Koren, Sergey, Uliano-Silva, Marcela, Chow, William, Fungtammasan, Arkarachai, Kim, Juwan, Lee, Chul, Ko, Byung June, Chaisson, Mark, Gedman, Gregory L, Cantin, Lindsey J, Thibaud-Nissen, Francoise, Haggerty, Leanne, Bista, Iliana, Smith, Michelle, Haase, Bettina, Mountcastle, Jacquelyn, Winkler, Sylke, Paez, Sadye, Howard, Jason, Vernes, Sonja C, Lama, Tanya M, Grutzner, Frank, Warren, Wesley C, Balakrishnan, Christopher N, Burt, Dave, George, Julia M, Biegler, Matthew T, Iorns, David, Digby, Andrew, Eason, Daryl, Robertson, Bruce, Edwards, Taylor, Wilkinson, Mark, Turner, George, Meyer, Axel, Kautt, Andreas F, Franchini, Paolo, Detrich, H William, Svardal, Hannes, Wagner, Maximilian, Naylor, Gavin JP, Pippel, Martin, Malinsky, Milan, Mooney, Mark, Simbirsky, Maria, Hannigan, Brett T, Pesout, Trevor, Houck, Marlys, Misuraca, Ann, Kingan, Sarah B, Hall, Richard, Kronenberg, Zev, Sović, Ivan, Dunn, Christopher, Ning, Zemin, Hastie, Alex, Lee, Joyce, Selvaraj, Siddarth, Green, Richard E, Putnam, Nicholas H, Gut, Ivo, Ghurye, Jay, Garrison, Erik, Sims, Ying, Collins, Joanna, Pelan, Sarah, Torrance, James, Tracey, Alan, Wood, Jonathan, Dagnew, Robel E, Guan, Dengfeng, London, Sarah E, Clayton, David F, Mello, Claudio V, Friedrich, Samantha R, Lovell, Peter V, Osipova, Ekaterina, Al-Ajli, Farooq O, Secomandi, Simona, Kim, Heebal, Theofanopoulou, Constantina, Hiller, Michael, Zhou, Yang, Harris, Robert S, Makova, Kateryna D, Medvedev, Paul, Hoffman, Jinna, Masterson, Patrick, Clark, Karen, Martin, Fergal, Howe, Kevin, Flicek, Paul, Walenz, Brian P, Kwak, Woori, Clawson, Hiram, Diekhans, Mark, Nassar, Luis, Paten, Benedict, Kraus, Robert HS, Crawford, Andrew J, Gilbert, M Thomas P, Zhang, Guojie, Venkatesh, Byrappa, Murphy, Robert W, Koepfli, Klaus-Peter, Shapiro, Beth, Johnson, Warren E, Di Palma, Federica, Marques-Bonet, Tomas, Teeling, Emma C, Warnow, Tandy, Graves, Jennifer Marshall, Ryder, Oliver A, Haussler, David, O'Brien, Stephen J, Korlach, Jonas, Lewin, Harris A, Howe, Kerstin, Myers, Eugene W, Durbin, Richard, Phillippy, Adam M, and Jarvis, Erich D

Subjects
Genome, Sex Chromosomes, High-Throughput Nucleotide Sequencing, Molecular Sequence Annotation, Genomics, Sequence Analysis, DNA, Birds, Genome Size, Haplotypes, Genome, Mitochondrial, Vertebrates, Animals, 14. Life underwater, Sequence Alignment, Gene Library
Abstract

High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species1-4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. We confirm that long-read sequencing technologies are essential for maximizing genome quality, and that unresolved complex repeats and haplotype heterozygosity are major sources of assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences.

121. Towards complete and error-free genome assemblies of all vertebrate species

Author

Rhie, Arang, McCarthy, Shane A., Fedrigo, Olivier, Damas, Joana, Formenti, Giulio, Koren, Sergey, Uliano-Silva, Marcela, Chow, William, Fungtammasan, Arkarachai, Kim, Juwan, Lee, Chul, Ko, Byung June, Chaisson, Mark, Gedman, Gregory L., Cantin, Lindsey J., Thibaud-Nissen, Francoise, Haggerty, Leanne, Bista, Iliana, Smith, Michelle, Haase, Bettina, Mountcastle, Jacquelyn, Winkler, Sylke, Paez, Sadye, Howard, Jason, Vernes, Sonja C., Lama, Tanya M., Grutzner, Frank, Warren, Wesley C., Balakrishnan, Christopher N., Burt, Dave, George, Julia M., Biegler, Matthew T., Iorns, David, Digby, Andrew, Eason, Daryl, Robertson, Bruce, Edwards, Taylor, Wilkinson, Mark, Turner, George, Meyer, Axel, Kautt, Andreas F., Franchini, Paolo, Detrich, H. William, Svardal, Hannes, Wagner, Maximilian, Naylor, Gavin J. P., Pippel, Martin, Malinsky, Milan, Mooney, Mark, Simbirsky, Maria, Hannigan, Brett T., Pesout, Trevor, Houck, Marlys, Misuraca, Ann, Kingan, Sarah B., Hall, Richard, Kronenberg, Zev, Sović, Ivan, Dunn, Christopher, Ning, Zemin, Hastie, Alex, Lee, Joyce, Selvaraj, Siddarth, Green, Richard E., Putnam, Nicholas H., Gut, Ivo, Ghurye, Jay, Garrison, Erik, Sims, Ying, Collins, Joanna, Pelan, Sarah, Torrance, James, Tracey, Alan, Wood, Jonathan, Dagnew, Robel E., Guan, Dengfeng, London, Sarah E., Clayton, David F., Mello, Claudio V., Friedrich, Samantha R., Lovell, Peter V., Osipova, Ekaterina, Al-Ajli, Farooq O., Secomandi, Simona, Kim, Heebal, Theofanopoulou, Constantina, Hiller, Michael, Zhou, Yang, Harris, Robert S., Makova, Kateryna D., Medvedev, Paul, Hoffman, Jinna, Masterson, Patrick, Clark, Karen, Martin, Fergal, Howe, Kevin, Flicek, Paul, Walenz, Brian P., Kwak, Woori, Clawson, Hiram, Diekhans, Mark, Nassar, Luis, Paten, Benedict, Kraus, Robert H. S., Crawford, Andrew J., Gilbert, M. Thomas P., Zhang, Guojie, Venkatesh, Byrappa, Murphy, Robert W., Koepfli, Klaus-Peter, Shapiro, Beth, Johnson, Warren E., Di Palma, Federica, Marques-Bonet, Tomas, Teeling, Emma C., Warnow, Tandy, Graves, Jennifer Marshall, Ryder, Oliver A., Haussler, David, O’Brien, Stephen J., Korlach, Jonas, Lewin, Harris A., Howe, Kerstin, Myers, Eugene W., Durbin, Richard, Phillippy, Adam M., and Jarvis, Erich D.

Subjects
45/91, 64, 631/61/212/2302, 706/648/697, 631/181/2474, 45, article, 45/23, 14. Life underwater, 631/181/735, 38
Abstract

High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species1–4. To address this issue, the international Genome 10K (G10K) consortium5, 6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. We confirm that long-read sequencing technologies are essential for maximizing genome quality, and that unresolved complex repeats and haplotype heterozygosity are major sources of assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences.

123. Towards complete and error-free genome assemblies of all vertebrate species

Author

Richard Hall, Tandy Warnow, Tanya M. Lama, Oliver A. Ryder, David Haussler, Matthew T. Biegler, Klaus-Peter Koepfli, Ivo Gut, Paul Flicek, Mark Chaisson, James Torrance, Guojie Zhang, Andrew J. Crawford, Federica Di Palma, Michael Hiller, Jennifer A. Marshall Graves, Sadye Paez, Sarah E. London, Mark Wilkinson, Kateryna D. Makova, Byung June Ko, Jimin George, Farooq O. Al-Ajli, Emma C. Teeling, George F. Turner, Robert H. S. Kraus, Sonja C. Vernes, Zev N. Kronenberg, Michelle Smith, Jonas Korlach, Daryl Eason, Jonathan Wood, Simona Secomandi, Claudio V. Mello, Arkarachai Fungtammasan, Arang Rhie, Tomas Marques-Bonet, Benedict Paten, Ekaterina Osipova, Richard Durbin, M. Thomas P. Gilbert, Beth Shapiro, Ivan Sović, Bruce C. Robertson, Richard E. Green, Eugene W. Myers, Leanne Haggerty, Sergey Koren, Martin Pippel, Bettina Haase, Patrick Masterson, Jay Ghurye, Maria Simbirsky, Samantha R. Friedrich, Chul Hee Lee, Luis R Nassar, Lindsey J. Cantin, Kerstin Howe, Erich D. Jarvis, Marlys L. Houck, Jason T. Howard, Jacquelyn Mountcastle, Mark Mooney, Paolo Franchini, Giulio Formenti, Siddarth Selvaraj, Robel E. Dagnew, Brett T. Hannigan, Brian P. Walenz, Alan Tracey, Heebal Kim, Constantina Theofanopoulou, Nicholas H. Putnam, Karen Clark, Iliana Bista, H. William Detrich, Dengfeng Guan, David Iorns, Andrew Digby, Trevor Pesout, Zemin Ning, Gregory Gedman, Woori Kwak, Maximilian Wagner, Joanna Collins, Harris A. Lewin, Hannes Svardal, Milan Malinsky, Byrappa Venkatesh, Françoise Thibaud-Nissen, Joana Damas, Andreas F. Kautt, Olivier Fedrigo, Christopher Dunn, William Chow, Warren E. Johnson, Yang Zhou, Adam M. Phillippy, Taylor Edwards, Paul Medvedev, Peter V. Lovell, Joyce V. Lee, Sylke Winkler, Stephen J. O'Brien, Wesley C. Warren, Alex Hastie, Marcela Uliano-Silva, Kevin L. Howe, Sarah B. Kingan, Fergal J. Martin, Christopher N. Balakrishnan, David F. Clayton, Ying Sims, Robert W. Murphy, Axel Meyer, Dave W Burt, Shane A. McCarthy, Sarah Pelan, Erik Garrison, Mark Diekhans, Frank Grützner, Gavin J. P. Naylor, Robert S. Harris, Hiram Clawson, Jinna Hoffman, Ann C Misuraca, J. H. Kim, University of St Andrews. School of Biology, University of St Andrews. St Andrews Bioinformatics Unit, Rhie, Arang [0000-0002-9809-8127], Fedrigo, Olivier [0000-0002-6450-7551], Formenti, Giulio [0000-0002-7554-5991], Koren, Sergey [0000-0002-1472-8962], Uliano-Silva, Marcela [0000-0001-6723-4715], Thibaud-Nissen, Francoise [0000-0003-4957-7807], Mountcastle, Jacquelyn [0000-0003-1078-4905], Winkler, Sylke [0000-0002-0915-3316], Vernes, Sonja C. [0000-0003-0305-4584], Grutzner, Frank [0000-0002-3088-7314], Balakrishnan, Christopher N. [0000-0002-0788-0659], Burt, Dave [0000-0002-9991-1028], George, Julia M. [0000-0001-6194-6914], Digby, Andrew [0000-0002-1870-8811], Robertson, Bruce [0000-0002-5348-2731], Edwards, Taylor [0000-0002-7235-6175], Meyer, Axel [0000-0002-0888-8193], Kautt, Andreas F. [0000-0001-7792-0735], Franchini, Paolo [0000-0002-8184-1463], Detrich, H. William, III [0000-0002-0783-4505], Pippel, Martin [0000-0002-8134-5929], Malinsky, Milan [0000-0002-1462-6317], Kingan, Sarah B. [0000-0002-4900-0189], Hall, Richard [0000-0001-6490-8227], Dunn, Christopher [0000-0002-0601-3254], Lee, Joyce [0000-0002-3492-1102], Putnam, Nicholas H. [0000-0002-1315-782X], Gut, Ivo [0000-0001-7219-632X], Tracey, Alan [0000-0002-4805-9058], Guan, Dengfeng [0000-0002-6376-3940], London, Sarah E. [0000-0002-7839-2644], Clayton, David F. [0000-0002-6395-3488], Mello, Claudio V. [0000-0002-9826-8421], Friedrich, Samantha R. [0000-0003-0570-6080], Osipova, Ekaterina [0000-0002-6769-7223], Al-Ajli, Farooq O. [0000-0002-4692-7106], Secomandi, Simona [0000-0001-8597-6034], Kim, Heebal [0000-0003-3064-1303], Theofanopoulou, Constantina [0000-0003-2014-7563], Zhou, Yang [0000-0003-1247-5049], Martin, Fergal [0000-0002-1672-050X], Flicek, Paul [0000-0002-3897-7955], Walenz, Brian P. [0000-0001-8431-1428], Diekhans, Mark [0000-0002-0430-0989], Paten, Benedict [0000-0001-8863-3539], Crawford, Andrew J. [0000-0003-3153-6898], Gilbert, M. Thomas P. [0000-0002-5805-7195], Zhang, Guojie [0000-0001-6860-1521], Venkatesh, Byrappa [0000-0003-3620-0277], Shapiro, Beth [0000-0002-2733-7776], Johnson, Warren E. [0000-0002-5954-186X], Marques-Bonet, Tomas [0000-0002-5597-3075], Teeling, Emma C. [0000-0002-3309-1346], Ryder, Oliver A. [0000-0003-2427-763X], Haussler, David [0000-0003-1533-4575], Korlach, Jonas [0000-0003-3047-4250], Lewin, Harris A. [0000-0002-1043-7287], Howe, Kerstin [0000-0003-2237-513X], Myers, Eugene W. [0000-0002-6580-7839], Durbin, Richard [0000-0002-9130-1006], Phillippy, Adam M. [0000-0003-2983-8934], Jarvis, Erich D. [0000-0001-8931-5049], Apollo - University of Cambridge Repository, National Institutes of Health (US), National Human Genome Research Institute (US), Ministry of Health and Welfare (South Korea), Wellcome Trust, European Molecular Biology Laboratory, Howard Hughes Medical Institute, Rockefeller University, Robert and Rosabel Osborne Endowment, European Commission, National Library of Medicine (US), Korea Institute of Marine Science & Technology, Ministry of Oceans and Fisheries (South Korea), Alfred P. Sloan Foundation, Max Planck Society, Maine Department of Inland Fisheries & Wildlife, National Science Foundation (US), University of Queensland, Science Exchange, Northeastern University (US), Federal Ministry of Education and Research (Germany), EMBO, National Key Research and Development Program (China), Qatar Society of Al-Gannas (Algannas), Katara Cultural Village, Government of Qatar, Monash University Malaysia, Hessen State Ministry of Higher Education, Research and the Arts, Ministry of Science, Research and Art Baden-Württemberg, Agency for Science, Technology and Research A*STAR (Singapore), European Research Council, Ministerio de Ciencia, Innovación y Universidades (España), Fundación 'la Caixa', Generalitat de Catalunya, Irish Research Council, Danish National Research Foundation, Australian Research Council, Vernes, Sonja C [0000-0003-0305-4584], Balakrishnan, Christopher N [0000-0002-0788-0659], George, Julia M [0000-0001-6194-6914], Kautt, Andreas F [0000-0001-7792-0735], Detrich, H William [0000-0002-0783-4505], Kingan, Sarah B [0000-0002-4900-0189], Putnam, Nicholas H [0000-0002-1315-782X], London, Sarah E [0000-0002-7839-2644], Clayton, David F [0000-0002-6395-3488], Mello, Claudio V [0000-0002-9826-8421], Friedrich, Samantha R [0000-0003-0570-6080], Al-Ajli, Farooq O [0000-0002-4692-7106], Walenz, Brian P [0000-0001-8431-1428], Crawford, Andrew J [0000-0003-3153-6898], Gilbert, M Thomas P [0000-0002-5805-7195], Johnson, Warren E [0000-0002-5954-186X], Teeling, Emma C [0000-0002-3309-1346], Ryder, Oliver A [0000-0003-2427-763X], Lewin, Harris A [0000-0002-1043-7287], Myers, Eugene W [0000-0002-6580-7839], Phillippy, Adam M [0000-0003-2983-8934], and Jarvis, Erich D [0000-0001-8931-5049]

Subjects
QH301 Biology, Genome, 0302 clinical medicine, Genome Size, Vertebrats, Uncategorized, 64, 0303 health sciences, Sex Chromosomes, Multidisciplinary, High-Throughput Nucleotide Sequencing, Genomics, Mitochondrial, Vertebrates, Identification (biology), Engineering sciences. Technology, Sequence Analysis, Neuroinformatics, 45/23, QH426 Genetics, Biology, Article, Evolutionary genetics, 38, Birds, QH301, 03 medical and health sciences, Molecular evolution, ddc:570, Genome assembly algorithms, Animals, 631/181/735, 14. Life underwater, Genomes, QH426, Gene, Gene Library, Genome, Mitochondrial, Haplotypes, Molecular Sequence Annotation, Sequence Alignment, Sequence Analysis, DNA, 030304 developmental biology, 45/91, 631/61/212/2302, 45, Human evolutionary genetics, Haplotype, DAS, DNA, Research data, 706/648/697, 631/181/2474, Evolutionary biology, Genètica, 030217 neurology & neurosurgery, Reference genome
Abstract

High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species1,2,3,4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. We confirm that long-read sequencing technologies are essential for maximizing genome quality, and that unresolved complex repeats and haplotype heterozygosity are major sources of assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences., We thank them for their permission to publish. A.R., S.K., B.P.W. and A.M.P. were supported by the Intramural Research Program of the NHGRI, NIH (1ZIAHG200398). A.R. was also supported by the Korea Health Technology R&D Project through KHIDI, funded by the Ministry of Health & Welfare, Republic of Korea (HI17C2098). S.A.M., I.B. and R.D. were supported by Wellcome Trust grant WT207492; W.C., M. Smith, Z.N., Y.S., J.C., S. Pelan, J.T., A.T., J.W. and Kerstin Howe by WT206194; L.H., F.M., Kevin Howe and P. Flicek by WT108749/Z/15/Z, WT218328/B/19/Z and the European Molecular Biology Laboratory. O.F. and E.D.J. were supported by Howard Hughes Medical Institute and Rockefeller University start-up funds for this project. J.D. and H.A.L. were supported by the Robert and Rosabel Osborne Endowment. M.U.-S. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement (750747). F.T.-N., J. Hoffman, P. Masterson and K.C. were supported by the Intramural Research Program of the NLM, NIH. C.L., B.J.K., J. Kim and H.K. were supported by the Marine Biotechnology Program of KIMST, funded by the Ministry of Ocean and Fisheries, Republic of Korea (20180430). M.C. was supported by Sloan Research Fellowship (FG-2020-12932). S.C.V. was funded by a Max Planck Research Group award from the Max Planck Society, and a Human Frontiers Science Program (HFSP) Research grant (RGP0058/2016). T.M.L., W.E.J. and the Canada lynx genome were funded by the Maine Department of Inland Fisheries & Wildlife (F11AF01099), including when W.E.J. held a National Research Council Research Associateship Award at the Walter Reed Army Institute of Research (WRAIR). C.B. was supported by the NSF (1457541 and 1456612). D.B. was funded by The University of Queensland (HFSP - RGP0030/2015). D.I. was supported by Science Exchange Inc. (Palo Alto, CA). H.W.D. was supported by NSF grants (OPP-0132032 ICEFISH 2004 Cruise, PLR-1444167 and OPP-1955368) and the Marine Science Center at Northeastern University (416). G.J.P.N. and the thorny skate genome were funded by Lenfest Ocean Program (30884). M.P. was funded by the German Federal Ministry of Education and Research (01IS18026C). M. Malinsky was supported by an EMBO fellowship (ALTF 456-2016). The following authors’ contributions were supported by the NIH: S. Selvaraj (R44HG008118); C.V.M., S.R.F., P.V.L. (R21 DC014432/DC/NIDCD); K.D.M. (R01GM130691); H.C. (5U41HG002371-19); M.D. (U41HG007234); and B.P. (R01HG010485). D.G. was supported by the National Key Research and Development Program of China (2017YFC1201201, 2018YFC0910504 and 2017YFC0907503). F.O.A. was supported by Al-Gannas Qatari Society and The Cultural Village Foundation-Katara, Doha, State of Qatar and Monash University Malaysia. C.T. was supported by The Rockefeller University. M. Hiller was supported by the LOEWE-Centre for Translational Biodiversity Genomics (TBG) funded by the Hessen State Ministry of Higher Education, Research and the Arts (HMWK). H.C. was supported by the NHGRI (5U41HG002371-19). R.H.S.K. was funded by the Max Planck Society with computational resources at the bwUniCluster and BinAC funded by the Ministry of Science, Research and the Arts Baden-Württemberg and the Universities of the State of Baden-Württemberg, Germany (bwHPC-C5). B.V. was supported by the Biomedical Research Council of A*STAR, Singapore. T.M.-B. was funded by the European Research Council under the European Union’s Horizon 2020 research and innovation programme (864203), MINECO/FEDER, UE (BFU2017-86471-P), Unidad de Excelencia María de Maeztu, AEI (CEX2018-000792-M), a Howard Hughes International Early Career award, Obra Social “La Caixa” and Secretaria d’Universitats i Recerca and CERCA Programme del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880). E.C.T. was supported by the European Research Council (ERC-2012-StG311000) and an Irish Research Council Laureate Award. M.T.P.G. was supported by an ERC Consolidator Award 681396-Extinction Genomics, and a Danish National Research Foundation Center Grant (DNRF143). T.W. was supported by the NSF (1458652). J. M. Graves was supported by the Australian Research Council (CEO561477). E.W.M. was partially supported by the German Federal Ministry of Education and Research (01IS18026C). Complementary sequencing support for the Anna’s hummingbird and several genomes was provided by Pacific Biosciences, Bionano Genomics, Dovetail Genomics, Arima Genomics, Phase Genomics, 10X Genomics, NRGene, Oxford Nanopore Technologies, Illumina, and DNAnexus. All other sequencing and assembly were conducted at the Rockefeller University, Sanger Institute, and Max Planck Institute Dresden genome labs. Part of this work used the computational resources of the NIH HPC Biowulf cluster (https://hpc.nih.gov). We acknowledge funding from the Wellcome Trust (108749/Z/15/Z) and the European Molecular Biology Laboratory., With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2018-000792-M).

Published
2021

124. Finding the genes, losing the organism.

Author

Bailey, Pat, Clayton, David F., Robinson, Gene E., Albertson, Craig, Carey, Hannah V., Cummings, Molly E., Hofmann, Hans A., Stanzione, Daniel C., Dewar, Ken, Meaney, Michael J., Edwards, Scott V., Gross, Louis J., Kingsolver, Joel G., Schlinger, Barney A., Shingleton, Alexander W., Sokolowski, Marla B., Somero, George N., and Todgham, Anne E.

Subjects
ORGANISMS, ENVIRONMENTAL exposure, CYTOLOGY, MOLECULAR biology, GENETICS
Abstract

The article talks about research on genetic variation and the holistic study of organisms. In an article in the June 2013 issue of the BioScience journal, the authors propose a renewed emphasis on the study of individual organisms taking into account the environmental exposures they are subjected to on top of their genetic variations. This is in consideration of the gene focused biological research which includes cellular and molecular biology and quantitative genetics.

Published
2013

125. Nigral and Cortical Lewy Bodies and Dystrophic Nigral Neurites in Parkinson's Disease and Cortical Lewy Body Disease Contain a-synuclein Immunoreactivity

Author

Irizarry, Michael C., Growdon, Whitfield, Gomez-Isla, Teresa, Newell, Kathy, George, Julia M., Clayton, David F., and Hyman, Bradley T.

Abstract

A mutation in the α-synuclein gene has recently been linked to some cases of familial Parkinson's disease (PD). We characterized the expression of this presynaptic protein in the midbrain, striatum, and temporal cortex of control, PD, and dementia with Lewy bodies (DLB) brain. Control brain showed punctate pericellular immunostaining. PD brain demonstrated α-synuclein immunoreactivity in nigral Lewy bodies, pale bodies and abnormal neurites. Rare neuronal soma in PD brain were immunoreactive for α-synuclein. DLB cases demonstrated these findings as well as α-synuclein immunoreactivity in cortical Lewy bodies and CA2-3 neurites. These results suggest that, even in sporadic cases, there is an early and direct role for α-synuclein in the pathogenesis of PD and the neuropathologically related disorder DLB.

Published
1998
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126. Activation and habituation of extracellular signal-regulated kinase phosphorylation in zebra finch auditory forebrain during song presentation.

Author

Cheng HY and Clayton DF

Subjects
Acoustic Stimulation, Animals, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases antagonists & inhibitors, Habituation, Psychophysiologic, Immediate-Early Proteins genetics, Phosphorylation, Transcriptional Activation, Auditory Cortex metabolism, Extracellular Signal-Regulated MAP Kinases metabolism, Immediate-Early Proteins biosynthesis, Songbirds metabolism
Abstract

The sound of tape-recorded birdsong triggers a set of behavioral and physiological responses in zebra finches, including transcriptional activation of the zenk gene in the auditory forebrain. Song repetition leads to the stimulus-specific habituation of these responses. To gain insight into the mechanisms that couple auditory experience to gene regulation, we monitored the phosphorylation of the zebra finch extracellular signal-regulated kinase (ERK) protein by immunoblotting. Initial presentations of novel song (but not tones or noise) resulted in a rapid increase in ERK phosphorylation, followed by a return to basal levels within 5 min. This response was localized to the auditory forebrain where the zenk gene is activated. Sustained repetition of one song caused a selective habituation of the ERK response: a different song triggered another cycle of ERK phosphorylation without altering the habituated response to the first. To test directly for a role of ERK in experience-dependent zenk gene regulation, we infused an inhibitor of mitogen-activated and extracellular-regulated protein kinase kinase (MEK-1; the enzyme responsible for ERK activation) unilaterally into one auditory lobule just before song stimulation. The song-induced increase in zenk mRNA was blocked on the side of the injection, but not on the contralateral (uninfused) side. These results show that ERK phosphorylation is necessary for the initiation of the zenk gene response to novel song and identify ERK as a plausible site of signal integration underlying the selective habituation of genomic responses to a repeated song.

Published
2004
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