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Certain variants in the PSPH gene, which encodes an enzyme called phosphoserine phosphatase, prevent the body from making sufficient amounts of the amino acid L-serine, leading to a range of nervous system problems. New research in FEBS Open Bio reveals that PSPH in ancient human genomes differed functionally from modern and disease-associated versions of the gene.
Investigators found that the modern human DNA sequence of PSPH differs from sequences identified in ancient hunter-gatherers. In evolution-guided yeast complementation assays, modern-day human phosphoserine phosphatase had the greatest functionality, with ancient proteins showing diminished function and disease-associated variants exhibiting the weakest function.
“Our study highlights the potential of combining evolution-guided variant prioritization with scalable heterologous assays to uncover functional differences that may otherwise remain overlooked,” said co-corresponding author Alexander DeLuna, Ph.D., of the Center for Research and Advanced Studies (CINVESTAV) in Mexico.
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Evolution-guided yeast complementation reveals functional differences in human PSPH variants, FEBS Open Bio (2026). DOI: 10.1002/2211-5463.70308
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New insights into the evolution of a gene linked to neurodevelopmental conditions (2026, August 5)
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