Modern human versions of the PSPH gene produce the brain-critical amino acid L-serine more efficiently than ancient hunter-gatherer versions, according to a new study in FEBS Open Bio.
The Research
The PSPH gene encodes phosphoserine phosphatase, an enzyme that helps synthesize L-serine — an amino acid essential for central nervous system development, synaptic plasticity, and myelin sheath maintenance. When PSPH function is impaired, L-serine production drops, leading to severe neurological problems including microcephaly, seizures, and developmental delays.
Researchers led by Alexander DeLuna, PhD, at the Center for Research and Advanced Studies (CINVESTAV) in Mexico, along with co-authors Mauricio Campa-Álvarez, Diana Ascencio, Miguel Vallebueno-Estrada, and colleagues, examined how the PSPH gene evolved across human history. The team used evolution-guided yeast complementation assays — a method where human PSPH gene variants are expressed in yeast cells missing their native equivalent. By measuring how well each human variant restored yeast growth through L-serine synthesis, the researchers could directly compare enzymatic strength across variants.
The results showed a clear functional gradient. Modern human PSPH sequences demonstrated the highest enzymatic activity. Ancient hunter-gatherer versions showed noticeably diminished function. Disease-associated PSPH variants — those linked to known pathogenic mutations — exhibited the weakest functional performance of all.
The study was published in FEBS Open Bio (DOI: 10.1002/2211-5463.70308) and is open access. The research team emphasizes that the stepwise increase in PSPH function from ancient to modern humans suggests evolutionary selective pressures favored enhanced L-serine synthesis, potentially supporting the growing metabolic demands of the modern human brain.
Why It Matters
L-serine isn't just any amino acid. It serves as a precursor for D-serine, a key neuromodulator involved in NMDA receptor signaling, and for complex lipids needed for brain development and myelin maintenance. The finding that modern humans carry a more efficient version of the PSPH enzyme than our hunter-gatherer ancestors hints at how brain biochemistry itself evolved to meet increasing cognitive demands.
For anyone interested in cognition, this study underscores a fundamental point: brain function depends on precise molecular machinery. Variations in genes like PSPH can subtly influence how efficiently your brain produces the building blocks it needs for learning, memory, and neural communication. While pathogenic PSPH mutations cause severe disorders, the study also reveals that even ancient, non-disease variants had reduced function — showing that small biochemical differences can accumulate over evolutionary time.
What You Can Do
You can't change your PSPH gene, but you can support the biochemical pathways it influences. L-serine is found in foods like soybeans, eggs, and sweet potatoes. Prioritizing sleep, regular exercise, and a nutrient-rich diet helps maintain overall brain health. If you're curious about how your own cognitive abilities compare, a validated assessment can offer useful perspective.
"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
Source: Neuroscience News
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