Coexpression reveals conserved mechanisms of transcriptional cell identity

Abstract

What makes a mouse a mouse, and not a hamster? The answer lies in the genome, and more specifically, in differences in gene regulation between the two organisms: where and when each gene is expressed. To quantify differences, a typical study will either compare functional genomics data from homologous tissues, limiting the approach to closely related species; or compare gene repertoires, limiting the resolution of the analysis to gross correlations between phenotypes and gene family size. As an alternative, gene coexpression networks provide a basis for studying the evolution of gene regulation without these constraints. By incorporating data from hundreds of independent experiments, meta-analytic coexpression networks reflect the convergent output of species-specific transcriptional regulation. In this work, we develop a measure of regulatory evolution based on gene coexpression. Comparing data from 14 species, we quantify the conservation of coexpression patterns 1) as a function of evolutionary time, 2) across orthology prediction algorithms, and 3) with reference to cell- and tissue-specificity. Strikingly, we uncover deeply conserved patterns of gradient-like expression across cell types from both the animal and plant kingdoms. These results suggest that ancient genes contribute to transcriptional cell identity through mechanisms that are independent of duplication and divergence.