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We characterized general transcriptional activity and variability of eukaryotic genes from global expression profiles of human, mouse, rat, fly, plants, and yeast. The variability shows a higher degree of divergence between distant species, implying that it is more closely related to phenotypic evolution, than the activity. More specifically, we show that transcriptional variability should be a true indicator of evolutionary rate. If we rule out the effect of translational selection, which seems to operate only in yeast, the apparent slow evolution of highly expressed genes should be attributed to their low variability. Meanwhile, rapidly evolving genes may acquire a high level of transcriptional variability and contribute to phenotypic variations. Essentiality also seems to be correlated with the variability, not the activity. We show that indispensable or highly interactive proteins tend to be present in high abundance to maintain a low variability. Our results challenge the current theory that highly expressed genes are essential and evolve slowly. Transcriptional variability, rather than transcriptional activity, might be a common indicator of essentiality and evolutionary rate, contributing to the correlation between the two variables.

Impact of Transcriptional Properties on Essentiality and Evolutionary Rate