Developmental and tissue expression breadth define distinct but overlapping classes of housekeeping genes

Housekeeping genes are commonly defined as broadly expressed genes that support essential cellular function. However, their identification in genome-wide datasets typically relies on spatial variation across adult tissues, while largely overlooking developmental time as an additional dimension of gene expression diversity. Here, we systematically compare gene expression breadth across developmental stages and adult tissues using zebrafish ( Danio rerio ) transcriptomic datasets that span embryogenesis and differentiated tissues. We classify genes according to their temporal expression breadth during development and examine how these patterns relate to traditional tissue-based definitions of housekeeping genes. As expected, developmental and adult expression breadth show only partial concordance: while a core set of genes is broadly expressed across both dimensions, many genes that are ubiquitous across adult tissues exhibit restricted expression during embryogenesis, and some genes expressed throughout development later become tissue-specific. Genes expressed across all developmental stages are enriched for fundamental cellular processes, show strong evolutionary conservation, and are associated with highly pleiotropic phenotypes. Notably, genes expressed during restricted developmental windows—particularly around gastrulation—can also play essential roles. These results highlight that expression ubiquity depends on both temporal and spatial context and underscore the importance of considering both dimensions explicitly when identifying and interpreting broadly expressed genes. More broadly, our analysis provides a framework for comparing developmental and tissue expression breadth and for exploring how gene expression dynamics across the life cycle relate to functional and evolutionary constraints.