Evolutionary conservation of the fidelity of transcription

Accurate transcription is required for the faithful expression of genetic information. Surprisingly though, little is known about the molecular mechanisms that control the fidelity of transcription, or the conservation of these mechanisms across the tree of life. To address this issue, we measured the error rate of transcription in five organisms of increasing complexity and identified various genes, alleles and processes that control transcriptional fidelity in multicellular organisms. In doing so, they highlight the evolutionary conservation of fidelity factors and open up new opportunities to probe the impact of transcription errors on intact organisms and human physiology. Finally, our experiments provide the first reasonable estimate of the error rate of transcription in human cells, identify the first disease associated with error-prone RNA polymerases and suggest that transcription errors may have contributed to the evolution of our genetic code.