Scientists have long known that humans develop more slowly than mice, but the molecular reasons behind that difference have been difficult to pin down. A new study points to a broad, system-wide pattern inside human cells that may help explain it.
Researchers from the Ebisuya Group at EMBL Barcelona and PoL-TU Dresden, working with the Savitski Team at EMBL Heidelberg, analyzed about 4,000 proteins shared between humans and mice. According to a report published in Developmental Cell, they found a clear overall tendency for proteins to persist longer in human cells than in mouse cells.
Protein degradation is the cellular process of breaking down proteins into amino acids. The recycling system keeps cells healthy, and during embryo development it plays a role in setting the pace of the segmentation clock, which controls how quickly body segments form along the developing spine.
Earlier work from the same group had already shown that a developmental protein called HES7 degrades more slowly in human cells than in mouse cells, slowing the human segmentation clock. The new study asked whether that difference was limited to HES7 or extended across a much wider range of proteins.
The answer was the latter. Not every protein followed the same pattern, and some proteins degraded more slowly in mouse cells. But across the 4,000 proteins studied, the tendency was consistent.
"Initially, we expected to find a special type of proteins that are degraded differently between species," said Miki Ebisuya, group leader at PoL-TU Dresden, former EMBL group leader and senior author of the work. "Instead, we discovered that slower protein degradation in humans is a general feature across the proteome."
The difference was not tied to any particular protein type or location within the cell. Proteins with widely different functions showed similar patterns. The slower degradation in human cells appeared regardless of whether proteins were broken down through the proteasome or the lysosome, two distinct cellular systems for disposing of old proteins.
That breadth was significant. It suggested the difference was not a feature of specific proteins but rather something more fundamental about human cells themselves.
To investigate what drives the pattern, the Ebisuya Group examined cellular metabolism. When they reduced metabolic activity in mouse cells, protein degradation slowed, and the cells began to behave more like human cells in terms of both degradation rate and developmental speed. The findings identify metabolism as a key regulator of how quickly cells turn over their proteins, and they connect metabolic rate directly to the pace of development.
The research provides a framework for understanding why developmental timing differs across species, and it opens questions about what else metabolic rate may govern at the cellular level.
