An Abundance of Ubiquitously Expressed Genes Revealed by Tissue Transcriptome Sequence Data

Abstract

The parts of the genome transcribed by a cell or tissue reflect the biological processes and functions it carries out. We characterized the features of mammalian tissue transcriptomes at the gene level through analysis of RNA deep sequencing (RNA-Seq) data across human and mouse tissues and cell lines. We observed that roughly 8,000 protein-coding genes were ubiquitously expressed, contributing to around 75% of all mRNAs by message copy number in most tissues. These mRNAs encoded proteins that were often intracellular, and tended to be involved in metabolism, transcription, RNA processing or translation. In contrast, genes for secreted or plasma membrane proteins were generally expressed in only a subset of tissues. The distribution of expression levels was broad but fairly continuous: no support was found for the concept of distinct expression classes of genes. Expression estimates that included reads mapping to coding exons only correlated better with qRT-PCR data than estimates which also included 3′ untranslated regions (UTRs). Muscle and liver had the least complex transcriptomes, in that they expressed predominantly ubiquitous genes and a large fraction of the transcripts came from a few highly expressed genes, whereas brain, kidney and testis expressed more complex transcriptomes with the vast majority of genes expressed and relatively small contributions from the most expressed genes. mRNAs expressed in brain had unusually long 3′UTRs, and mean 3′UTR length was higher for genes involved in development, morphogenesis and signal transduction, suggesting added complexity of UTR-based regulation for these genes. Our results support a model in which variable exterior components feed into a large, densely connected core composed of ubiquitously expressed intracellular proteins.

Author Summary

A variety of genes are active within the nuclei of our cells. Some are needed for the day-to-day maintenance of cell functions, while others have roles that are more specific to certain tissues or particular cell types; for example, only the pancreas produces insulin. As a result, every tissue has its own profile of gene activity. Since active genes produce RNA, tissue differences in gene activity can be probed by characterizing the RNA they contain. Essentially the entire set of RNAs or ‘transcriptome’ has been sequenced from various tissues, and we used these data to compare the degree of specialization of different tissues and to investigate the set of ‘core’ genes active in every tissue. A central observation was that there are an abundance of such core genes, and that these genes account for the majority of the transcriptome in each tissue. These findings will aid in the understanding of what makes tissues, and cell types, different from each other and what each requires to function.