What makes a mouse a mouse, and not a hamster? Differences in gene regulation between the two organisms play a critical role. Comparative analysis of gene coexpression networks provides a general framework for investigating the evolution of gene regulation across species. Here, we compare coexpression networks from 37 species and quantify the conservation of gene activity 1) as a function of evolutionary time, 2) across orthology prediction algorithms, and 3) with reference to cell- and tissue-specificity. We find that ancient genes are expressed in multiple cell types and have well conserved coexpression patterns, however they are expressed at different levels across cell types. Thus, differential regulation of ancient gene programs contributes to transcriptional cell identity. We propose that this differential regulation may play a role in cell diversification in both the animal and plant kingdoms.
© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.