The Reality of Pervasive Transcription

TLDR

Only about 1.2 % of the mammalian genome encodes proteins, yet evidence indicates that most of the genome is transcribed beyond known genes, a phenomenon called pervasive transcription. The study evaluates van Bakel et al.’s analysis of pervasive transcription and compares it to other independent studies. The authors find that pervasive transcription is supported by multiple techniques, that van Bakel’s results are atypical and limited by shallow sequencing, and that overall evidence strongly supports pervasive transcription though its biological significance remains unclear.

Abstract

Current estimates indicate that only about 1.2% of the mammalian genome codes for amino acids in proteins. However, mounting evidence over the past decade has suggested that the vast majority of the genome is transcribed, well beyond the boundaries of known genes, a phenomenon known as pervasive transcription [1]. Challenging this view, an article published in PLoS Biology by van Bakel et al. concluded that “the genome is not as pervasively transcribed as previously reported” [2] and that the majority of the detected low-level transcription is due to technical artefacts and/or background biological noise. These conclusions attracted considerable publicity [3]–[6]. Here, we present an evaluation of the analysis and conclusions of van Bakel et al. compared to those of others and show that (1) the existence of pervasive transcription is supported by multiple independent techniques; (2) re-analysis of the van Bakel et al. tiling arrays shows that their results are atypical compared to those of ENCODE and lack independent validation; and (3) the RNA sequencing dataset used by van Bakel et al. suffered from insufficient sequencing depth and poor transcript assembly, compromising their ability to detect the less abundant transcripts outside of protein-coding genes. We conclude that the totality of the evidence strongly supports pervasive transcription of mammalian genomes, although the biological significance of many novel coding and noncoding transcripts remains to be explored.