Redefining Housekeeping Genes in the Context of Vertebrate Development

Housekeeping genes are typically defined as genes active in all adult tissues and essential for basic cellular functions. However, this view overlooks genes that are crucial during early development. Using zebrafish as a model system, we examined gene expression from the first hours of embryogenesis through adulthood. We found that many genes expressed throughout development remain broadly expressed in adults, but others do not; and some adult housekeeping genes are not active early on. This reveals that essential gene functions shift across life stages. Genes active throughout development are more likely to be evolutionarily ancient, shared with humans, and cause defects in many organs when disrupted. Yet some genes expressed only at specific developmental stages, especially around gastrulation, can be equally essential. This supports the developmental hourglass model, where mid-embryogenesis is the most conserved stage. Our results broaden the concept of housekeeping genes to include genes essential across time, not only across adult tissues.