RESUMEN
Designing effective and accurate tools for identifying the functional and structural elements in a genome remains at the frontier of genome annotation owing to incompleteness and inaccuracy of the data, limitations in the computational models, and shifting paradigms in genomics, such as alternative splicing. We present a methodology for the automated annotation of genes and their alternatively spliced mRNA transcripts based on existing cDNA and protein sequence evidence from the same species or projected from a related species using syntenic mapping information. At the core of the method is the splice graph, a compact representation of a gene, its exons, introns, and alternatively spliced isoforms. The putative transcripts are enumerated from the graph and assigned confidence scores based on the strength of sequence evidence, and a subset of the high-scoring candidates are selected and promoted into the annotation. The method is highly selective, eliminating the unlikely candidates while retaining 98% of the high-quality mRNA evidence in well-formed transcripts, and produces annotation that is measurably more accurate than some evidence-based gene sets. The process is fast, accurate, and fully automated, and combines the traditionally distinct gene annotation and alternative splicing detection processes in a comprehensive and systematic way, thus considerably aiding in the ensuing manual curation efforts.
Asunto(s)
Empalme Alternativo/genética , Genes/genética , Programas Informáticos , Animales , Gatos , Bovinos , Pollos/genética , Biología Computacional/métodos , Perros , Evolución Molecular , Genoma , Ratones , Modelos Genéticos , Pan troglodytes/genética , Papio/genética , Valor Predictivo de las Pruebas , Ratas , Programas Informáticos/normas , Porcinos/genética , Sintenía/genética , Takifugu/genética , Pez Cebra/genéticaRESUMEN
The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart.
Asunto(s)
Cromosomas/genética , Genoma Humano , Genoma , Ratones Endogámicos/genética , Análisis de Secuencia de ADN , Sintenía , Animales , Composición de Base , Cromosomas Humanos/genética , Biología Computacional , Secuencia Conservada , Bases de Datos de Ácidos Nucleicos , Evolución Molecular , Genes , Marcadores Genéticos , Genómica , Humanos , Ratones , Ratones Endogámicos A/genética , Ratones Endogámicos DBA/genética , Datos de Secuencia Molecular , Mapeo Físico de Cromosoma , Proteínas/química , Proteínas/genética , Alineación de Secuencia , Especificidad de la EspecieRESUMEN
Ty1 is the most successful of the five endogenous yeast retrotransposons. The life cycle of Ty1 dictates that a number of nucleocapsid (NC)-facilitated events occur although the protein(s) responsible for these events has not been identified. The positioning of the NC peptide is conserved at the carboxy terminus of the Gag protein among most long terminal repeat (LTR)-containing retroelements. An analogous region of Ty1 that simultaneously encodes part of Gag, protease (PR), and the C-terminal p4 peptide was mutagenized. Some of these mutations result in smaller-than-normal virus-like particles (VLPs). The mutants were also found to impair an NC-like functionality contained within the amino terminus of the protease that is distinct and separable from its proteolytic activity. Remarkably, these mutants have distinct defects in reverse transcription.