Why humans develop slower than mice may involve protein stability
A study in human and mouse developmental-cell models finds proteins persist longer in human cells, affecting the pace of key developmental processes.
By Priya Raghavan · Science Reporter
3 min read
New research into why humans develop slower than mice points to a broad difference in how quickly cells break down proteins. The work, published in Developmental Cell, found that proteins generally persisted longer in human induced presomitic mesoderm cells than in comparable mouse cells, linking protein stability to the timing of developmental processes.
The findings extend earlier work on one key developmental gene, HES7, to thousands of proteins in a defined human-and-mouse cell model. They do not show that protein stability alone accounts for developmental differences between the two species.
Why do humans develop slower than mice?
Proteins must be cleared after they have done their work, with their components recycled by the cell. Slower degradation means a protein remains present for longer before it is broken down. According to the European Molecular Biology Laboratory, this process helps set the pace of the segmentation clock, a repeating genetic activity involved in early body patterning.
The segmentation clock provides researchers with a way to study differences in developmental timing between species. The study says its cycle in human induced presomitic mesoderm cells is about twice as long as in equivalent mouse cells.
Researchers used dynamic stable isotope labeling, known as SILAC, to compare roughly 5,000 proteins in the two types of cells, according to the paper. They reported an overall pattern of slower degradation in the human cells across cellular locations and across the main degradation routes. The trend did not mean every protein behaved alike: an EMBL account of the work says some proteins were cleared more slowly in mouse cells.
Metabolism experiment changed mouse-cell timing
The team also tested whether metabolism affected protein stability. Inhibiting glycolysis in mouse induced presomitic mesoderm cells partly reproduced the human-like protein-stability pattern, the paper reports. The authors further found that changing protein stability altered both the segmentation clock's pace and cellular differentiation.
That result identifies protein stability as a mediator between metabolism and developmental tempo, rather than establishing a single master cause. The mouse experiment was a partial phenocopy, meaning it recreated only part of the profile seen in the human cells.
From HES7 to a broader pattern
Earlier research had shown that the HES7 protein was degraded more slowly in human cells and that other biochemical steps connected with HES7 also took longer, according to a 2020 report from RIKEN. Those experiments indicated that the timing difference depended on the cellular environment rather than on swapping the human and mouse versions of the gene.
The 2026 study asks whether that observation was limited to HES7. Its evidence supports a wider tendency in the human and mouse developmental-cell models examined, while leaving open how far the mechanism applies across tissues, stages of development or other species.
This story draws on original reporting from Phys.org.