Program in Gene Function and Expression; Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
Algorithms; Cells; Chimerin Proteins; Chromosomes, Human, Pair 1; Female; Gene Expression Profiling; Gene Regulatory Networks; Humans; Male; Microarray Analysis; Models, Biological; Nucleic Acid Amplification Techniques; RNA; RNA Isoforms; Transcription, Genetic; Transcriptome; Validation Studies as Topic
Biochemistry, Biophysics, and Structural Biology | Genetics and Genomics | Systems Biology
The classic organization of a gene structure has followed the Jacob and Monod bacterial gene model proposed more than 50 years ago. Since then, empirical determinations of the complexity of the transcriptomes found in yeast to human has blurred the definition and physical boundaries of genes. Using multiple analysis approaches we have characterized individual gene boundaries mapping on human chromosomes 21 and 22. Analyses of the locations of the 5' and 3' transcriptional termini of 492 protein coding genes revealed that for 85% of these genes the boundaries extend beyond the current annotated termini, most often connecting with exons of transcripts from other well annotated genes. The biological and evolutionary importance of these chimeric transcripts is underscored by (1) the non-random interconnections of genes involved, (2) the greater phylogenetic depth of the genes involved in many chimeric interactions, (3) the coordination of the expression of connected genes and (4) the close in vivo and three dimensional proximity of the genomic regions being transcribed and contributing to parts of the chimeric RNAs. The non-random nature of the connection of the genes involved suggest that chimeric transcripts should not be studied in isolation, but together, as an RNA network.