Important lessons from complex genomes

Abstract Text: The approximately three billion base pairs of the human DNA represent a storage devise encoding information for hundreds of thousands of processes that can go on within and outside of a human cell. This information is revealed in the RNAs that are composed of 12 billion nucleotides considering the strandedness and the allelic content each of the diploid copies of the genome.  Results stemming from the efforts to catalogue and analyze the RNA products made by cells in the human (ENCODE), fly-worm (modENCODE) and mouse ENCODE projects have shed light on both the functional content and how this information is organized by various genomes. In human cells, a total of ~161,000 transcripts present within ~50,000 genic regions represent our previously best manually-curated annotation (based on v 7 Gencode) of the transcriptome. The results from the ENCODE project point to considerable supplementation of these data. Analyses of these transcriptome data sets have resulted in important and under appreciated lessons such as: a) pervasive genome-wide transcription prompts a need to redefine the definition of a gene b) expression ranges follow transcript types and subcellular localization c) expression of isoforms of a gene by a cell do not follow a minimalistic strategy and d) genomic characteristics of potential trans-acting enhancer regions are distinguishable from other types of cis-acting regulatory regions. These and other lessons drawn from the landscape of both coding and non-coding RNAs present in eukaryotic cells have been used to assist in understanding and organizing what is often seen as dauntingly complex genomes.

Keywords: annotation, ENCODE, transcriptome