Study reveals evolutionary shift in gene crucial for the human nervous system

Certain variants in the PSPH gene, which encodes an enzyme called phosphoserine phosphatase, prevent the body from making sufficient amounts of 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 function, 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."

Alexander DeLuna, PhD, co-corresponding author, Center for Research and Advanced Studies (CINVESTAV), Mexico