Genome-wide transcription and the implications for genomic organization

Key Points In-depth analyses of the transcriptional outputs of eukaryotic genomes suggest that the information content of a genome is complex, and that this complexity manifests itself at two levels: the fraction of the genome that is devoted to encoding functional elements is higher than expected, and multiple functional elements can exist in a single region. The architecture of the eukaryotic transcriptome is clearly much more complex than could have been anticipated in terms of the number of nucleotides that are transcribed and the final arrangements of nucleotides that are present in mature processed RNA molecules. The complexity of genomic organization suggests that the currently accepted model, by which each region of DNA carries a single discrete function, must be re-evaluated, and an interleaved model for the arrangement of functional elements is more likely to represent the informational content of eukaryotic genomes. Despite the potential problems that are presented by use of the same genomic space for multiple purposes, the following advantages are brought by this complex genomic organization: an increase in protein-coding transcript diversity; a widespread adoption of RNA transcripts as regulatory agents; and a reliance on transcription as a regulatory process. On a global level, an interleaved genomic organization of functional elements seems to be preserved in different kingdoms, and the arrangement of specific overlapping functional elements is preserved among different species. This suggests that such a model does indeed provide advantages throughout evolution. Mutations at non-canonical sites, such as intronic regions that lie distal from splice sites, can affect fitness if they involve internal promoter regions, an exon of an overlapping transcript or a short RNA. Genome-wide analyses of transcriptional output in eukaryotes have revealed an unanticipated transcriptome complexity. These findings imply a complex, interleaved genomic organization, in which individual sequences carry multiple and overlapping informational content. The authors discuss the evidence for, and functional and evolutionary consequences of, this organization. Recent evidence of genome-wide transcription in several species indicates that the amount of transcription that occurs cannot be entirely accounted for by current sets of genome-wide annotations. Evidence indicates that most of both strands of the human genome might be transcribed, implying extensive overlap of