Fig. 3

Characterizing the relationship of cell-type and promoter sequence to transcriptomic divergence. a, b Divergence of co-expression modules (left—human-derived, right—mouse-derived, bottom—combined) stratified by cell type. Black box represents mean divergence score for each cell type and * represents a significant difference in cell-type divergence between the species. Glial enriched modules display the greatest divergence in human and mouse, with the exception of microglial modules which show strong divergence in human but not mouse. The cell-type color scheme applies to all panels of the figure—the microglial subclassification only applies from panel b onwards. c Module divergence scores of human modules with a microglial module set name. Microglial modules fall into two main classes—WB.M10 is more representative of homeostatic microglial markers, whereas WB.M8 is more representative of microglial activation. WB.M8 displays significantly (*; p < 0.05) stronger divergence than WB.M10. Dot color represents module cell-type annotation. d Module divergence scores of human modules with enrichment for either excitatory (Exc) or inhibitory (Inh) neuronal markers. There is no difference in divergence between the two subclasses. e Cell-type transcriptomic divergence is plotted for both human and mouse lineages. f Divergence Index (ratio of mean human- and mouse-module divergence scores) plotted for major cell types with point size reflecting absolute transcriptome divergence. Microglia display the greatest relative divergence. Error bars represent the 95% CI from permuting across study in that species. g Module divergence plotted against module-level sequence divergence. Promoter conservation was assessed by measuring sequence conservation of the 250 bp upstream of each gene using the mammalian PhastCons score. The conservation score for every gene in a module was averaged to produce a module sequence divergence score. Transcriptomic divergence significantly correlates (p < 0.01; cor = 0.27) with promoter sequence divergence across cell types but not for modules without cell-type enrichment (cor = − 0.04; pval = 1)