5 results on '"Cutter, Asher D."'
Search Results
2. Molecular correlates of genes exhibiting RNAi phenotypes in Caenorhabditis elegans
- Author
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Cutter, Asher D., Payseur, Bret A., Salcedo, Tovah, Estes, Anne M., Good, Jeffrey M., Wood, Elizabeth, Hartl, Thomas, Maughan, Heather, Strempel, Jannine, Wang, Baomin, Bryan, Anthony C., and Dellos, Melissa
- Subjects
DNA -- Genetic aspects ,Gene expression -- Physiological aspects ,Genetic research -- Analysis ,Genomes -- Physiological aspects ,Genomes -- Research ,Phenotype -- Genetic aspects ,Proteins -- Genetic aspects ,RNA -- Genetic aspects ,Health - Abstract
Research has been conducted on genome-wide links between genotype and phenotype. The authors have investigated this issue via establishing association between RNAi phenotypes in Caenorhabditis elegans and sequence characteristics of DNA and corresponding proteins, and they report that genes possessing RNAi phenotypes are long and highly expressed with little noncoding DNA.
- Published
- 2003
3. Comparative genomic analysis of upstream miRNA regulatory motifs in Caenorhabditis.
- Author
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Jovelin R, Krizus A, Taghizada B, Gray JC, Phillips PC, Claycomb JM, and Cutter AD
- Subjects
- Animals, Gene Expression Regulation, Phylogeny, Caenorhabditis genetics, MicroRNAs genetics, RNA, Helminth genetics, Regulatory Sequences, Nucleic Acid
- Abstract
MicroRNAs (miRNAs) comprise a class of short noncoding RNA molecules that play diverse developmental and physiological roles by controlling mRNA abundance and protein output of the vast majority of transcripts. Despite the importance of miRNAs in regulating gene function, we still lack a complete understanding of how miRNAs themselves are transcriptionally regulated. To fill this gap, we predicted regulatory sequences by searching for abundant short motifs located upstream of miRNAs in eight species of Caenorhabditis nematodes. We identified three conserved motifs across the Caenorhabditis phylogeny that show clear signatures of purifying selection from comparative genomics, patterns of nucleotide changes in motifs of orthologous miRNAs, and correlation between motif incidence and miRNA expression. We then validated our predictions with transgenic green fluorescent protein reporters and site-directed mutagenesis for a subset of motifs located in an enhancer region upstream of let-7 We demonstrate that a CT-dinucleotide motif is sufficient for proper expression of GFP in the seam cells of adult C. elegans, and that two other motifs play incremental roles in combination with the CT-rich motif. Thus, functional tests of sequence motifs identified through analysis of molecular evolutionary signatures provide a powerful path for efficiently characterizing the transcriptional regulation of miRNA genes., (© 2016 Jovelin et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)
- Published
- 2016
- Full Text
- View/download PDF
4. Full-genome evolutionary histories of selfing, splitting, and selection in Caenorhabditis.
- Author
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Thomas CG, Wang W, Jovelin R, Ghosh R, Lomasko T, Trinh Q, Kruglyak L, Stein LD, and Cutter AD
- Subjects
- Animals, Caenorhabditis elegans physiology, Inbreeding, Mutation, Self-Fertilization, Caenorhabditis elegans genetics, Evolution, Molecular, Genetic Speciation, Genome, Helminth, Selection, Genetic
- Abstract
The nematode Caenorhabditis briggsae is a model for comparative developmental evolution with C. elegans. Worldwide collections of C. briggsae have implicated an intriguing history of divergence among genetic groups separated by latitude, or by restricted geography, that is being exploited to dissect the genetic basis to adaptive evolution and reproductive incompatibility; yet, the genomic scope and timing of population divergence is unclear. We performed high-coverage whole-genome sequencing of 37 wild isolates of the nematode C. briggsae and applied a pairwise sequentially Markovian coalescent (PSMC) model to 703 combinations of genomic haplotypes to draw inferences about population history, the genomic scope of natural selection, and to compare with 40 wild isolates of C. elegans. We estimate that a diaspora of at least six distinct C. briggsae lineages separated from one another approximately 200,000 generations ago, including the "Temperate" and "Tropical" phylogeographic groups that dominate most samples worldwide. Moreover, an ancient population split in its history approximately 2 million generations ago, coupled with only rare gene flow among lineage groups, validates this system as a model for incipient speciation. Low versus high recombination regions of the genome give distinct signatures of population size change through time, indicative of widespread effects of selection on highly linked portions of the genome owing to extreme inbreeding by self-fertilization. Analysis of functional mutations indicates that genomic context, owing to selection that acts on long linkage blocks, is a more important driver of population variation than are the functional attributes of the individually encoded genes., (© 2015 Thomas et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2015
- Full Text
- View/download PDF
5. Comparative validation of the D. melanogaster modENCODE transcriptome annotation.
- Author
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Chen ZX, Sturgill D, Qu J, Jiang H, Park S, Boley N, Suzuki AM, Fletcher AR, Plachetzki DC, FitzGerald PC, Artieri CG, Atallah J, Barmina O, Brown JB, Blankenburg KP, Clough E, Dasgupta A, Gubbala S, Han Y, Jayaseelan JC, Kalra D, Kim YA, Kovar CL, Lee SL, Li M, Malley JD, Malone JH, Mathew T, Mattiuzzo NR, Munidasa M, Muzny DM, Ongeri F, Perales L, Przytycka TM, Pu LL, Robinson G, Thornton RL, Saada N, Scherer SE, Smith HE, Vinson C, Warner CB, Worley KC, Wu YQ, Zou X, Cherbas P, Kellis M, Eisen MB, Piano F, Kionte K, Fitch DH, Sternberg PW, Cutter AD, Duff MO, Hoskins RA, Graveley BR, Gibbs RA, Bickel PJ, Kopp A, Carninci P, Celniker SE, Oliver B, and Richards S
- Subjects
- Animals, Cluster Analysis, Drosophila melanogaster classification, Evolution, Molecular, Exons, Female, Genome, Insect, Humans, Male, Nucleotide Motifs, Phylogeny, Position-Specific Scoring Matrices, Promoter Regions, Genetic, RNA Editing, RNA Splice Sites, RNA Splicing, Reproducibility of Results, Transcription Initiation Site, Computational Biology methods, Drosophila melanogaster genetics, Gene Expression Profiling, Molecular Sequence Annotation, Transcriptome
- Abstract
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., (© 2014 Chen et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2014
- Full Text
- View/download PDF
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