%0 Journal Article %J Genome Res %D 2014 %T Comparative validation of the D. melanogaster modENCODE transcriptome annotation. %A Chen, Zhen-Xia %A Sturgill, David %A Qu, Jiaxin %A Jiang, Huaiyang %A Park, Soo %A Boley, Nathan %A Suzuki, Ana Maria %A Fletcher, Anthony R %A Plachetzki, David C %A FitzGerald, Peter C %A Artieri, Carlo G %A Atallah, Joel %A Barmina, Olga %A Brown, James B %A Blankenburg, Kerstin P %A Clough, Emily %A Dasgupta, Abhijit %A Gubbala, Sai %A Han, Yi %A Jayaseelan, Joy C %A Kalra, Divya %A Kim, Yoo-Ah %A Kovar, Christie L %A Lee, Sandra L %A Li, Mingmei %A Malley, James D %A Malone, John H %A Mathew, Tittu %A Mattiuzzo, Nicolas R %A Munidasa, Mala %A Muzny, Donna M %A Ongeri, Fiona %A Perales, Lora %A Przytycka, Teresa M %A Pu, Ling-Ling %A Robinson, Garrett %A Thornton, Rebecca L %A Saada, Nehad %A Scherer, Steven E %A Smith, Harold E %A Vinson, Charles %A Warner, Crystal B %A Worley, Kim C %A Wu, Yuan-Qing %A Zou, Xiaoyan %A Cherbas, Peter %A Kellis, Manolis %A Eisen, Michael B %A Piano, Fabio %A Kionte, Karin %A Fitch, David H %A Sternberg, Paul W %A Cutter, Asher D %A Duff, Michael O %A Hoskins, Roger A %A Graveley, Brenton R %A Gibbs, Richard A %A Bickel, Peter J %A Kopp, Artyom %A Carninci, Piero %A Celniker, Susan E %A Oliver, Brian %A Richards, Stephen %K Animals %K Cluster Analysis %K Computational Biology %K Drosophila melanogaster %K Evolution, Molecular %K Exons %K Female %K Gene Expression Profiling %K Genome, Insect %K Humans %K Male %K Molecular Sequence Annotation %K Nucleotide Motifs %K Phylogeny %K Position-Specific Scoring Matrices %K Promoter Regions, Genetic %K Reproducibility of Results %K RNA Editing %K RNA Splice Sites %K RNA Splicing %K Transcription Initiation Site %K Transcriptome %X

Accurate gene model annotation of reference genomes is critical for making them useful. The modENCODE project has improved the D. melanogaster genome annotation by using deep and diverse high-throughput data. Since transcriptional activity that has been evolutionarily conserved is likely to have an advantageous function, we have performed large-scale interspecific comparisons to increase confidence in predicted annotations. To support comparative genomics, we filled in divergence gaps in the Drosophila phylogeny by generating draft genomes for eight new species. For comparative transcriptome analysis, we generated mRNA expression profiles on 81 samples from multiple tissues and developmental stages of 15 Drosophila species, and we performed cap analysis of gene expression in D. melanogaster and D. pseudoobscura. We also describe conservation of four distinct core promoter structures composed of combinations of elements at three positions. Overall, each type of genomic feature shows a characteristic divergence rate relative to neutral models, highlighting the value of multispecies alignment in annotating a target genome that should prove useful in the annotation of other high priority genomes, especially human and other mammalian genomes that are rich in noncoding sequences. We report that the vast majority of elements in the annotation are evolutionarily conserved, indicating that the annotation will be an important springboard for functional genetic testing by the Drosophila community.

%B Genome Res %V 24 %P 1209-23 %8 2014 Jul %G eng %N 7 %1 https://www.ncbi.nlm.nih.gov/pubmed/24985915?dopt=Abstract %R 10.1101/gr.159384.113 %0 Journal Article %J Nature %D 2011 %T A high-resolution map of human evolutionary constraint using 29 mammals. %A Lindblad-Toh, Kerstin %A Garber, Manuel %A Zuk, Or %A Lin, Michael F %A Parker, Brian J %A Washietl, Stefan %A Kheradpour, Pouya %A Ernst, Jason %A Jordan, Gregory %A Mauceli, Evan %A Ward, Lucas D %A Lowe, Craig B %A Holloway, Alisha K %A Clamp, Michele %A Gnerre, Sante %A Alföldi, Jessica %A Beal, Kathryn %A Chang, Jean %A Clawson, Hiram %A Cuff, James %A Di Palma, Federica %A Fitzgerald, Stephen %A Flicek, Paul %A Guttman, Mitchell %A Hubisz, Melissa J %A Jaffe, David B %A Jungreis, Irwin %A Kent, W James %A Kostka, Dennis %A Lara, Marcia %A Martins, André L %A Massingham, Tim %A Moltke, Ida %A Raney, Brian J %A Rasmussen, Matthew D %A Robinson, Jim %A Stark, Alexander %A Vilella, Albert J %A Wen, Jiayu %A Xie, Xiaohui %A Zody, Michael C %A Baldwin, Jen %A Bloom, Toby %A Chin, Chee Whye %A Heiman, Dave %A Nicol, Robert %A Nusbaum, Chad %A Young, Sarah %A Wilkinson, Jane %A Worley, Kim C %A Kovar, Christie L %A Muzny, Donna M %A Gibbs, Richard A %A Cree, Andrew %A Dihn, Huyen H %A Fowler, Gerald %A Jhangiani, Shalili %A Joshi, Vandita %A Lee, Sandra %A Lewis, Lora R %A Nazareth, Lynne V %A Okwuonu, Geoffrey %A Santibanez, Jireh %A Warren, Wesley C %A Mardis, Elaine R %A Weinstock, George M %A Wilson, Richard K %A Delehaunty, Kim %A Dooling, David %A Fronik, Catrina %A Fulton, Lucinda %A Fulton, Bob %A Graves, Tina %A Minx, Patrick %A Sodergren, Erica %A Birney, Ewan %A Margulies, Elliott H %A Herrero, Javier %A Green, Eric D %A Haussler, David %A Siepel, Adam %A Goldman, Nick %A Pollard, Katherine S %A Pedersen, Jakob S %A Lander, Eric S %A Kellis, Manolis %K Animals %K Disease %K Evolution, Molecular %K Exons %K Genome %K Genome, Human %K Genomics %K Health %K Humans %K Mammals %K Molecular Sequence Annotation %K Phylogeny %K RNA %K Selection, Genetic %K Sequence Alignment %K Sequence Analysis, DNA %X

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.

%B Nature %V 478 %P 476-82 %8 2011 Oct 12 %G eng %N 7370 %1 https://www.ncbi.nlm.nih.gov/pubmed/21993624?dopt=Abstract %R 10.1038/nature10530