The Neanderthal Altai, Vi3315, and Vi3319 have a very special genetic mutation, the CYP21A2 rs6467 (C;T) variant. This mutation causes a form of nonclassic Congenital Adrenal Hyperplasia (NCAH). In simple terms: it weakened their ability to make cortisol, the body’s main stress hormone. This one genetic quirk may have had an outsized role in shaping Neanderthals and humanity. This hypothesis below explores how this single genetic variant may have shaped Neanderthal evolution and modern human adaptation.
Note: NCAH in modern humans is mild or even asymptomatic partially due to below mutations that Neanderthals passed on to us.
Neanderthals were highly interbred and NCAH put significant pressure on their numbers. Even modern children who inherited two bad copies of this mutation usually didn’t survive past birth. While this is seen in 1-2% of modern populations if we continue to find it in nearly all Neanderthals DNA that would mean significant species issues which would have kept populations small and fragile. That, in turn, created strong and consistent evolutionary pressure to adapt to NCAH.
Today we often credit Neanderthal DNA with boosting the human immune system. Cortisol modulates immune function and NCAH likely influenced selection to favor genetics that strengthened immune response.
Estrogen increases cortisol-binding globulin which reduces the effectiveness of the little cortisol that NCAH would produce and we see selection pressure to reduce estrogen signaling.
Three to highlight include: PGR V660L which by increases progesterone receptors which decreases estrogen signaling and improved myelination, and reduced estrogen by fast CYP1A1 which also makes it so today some can have caffeine even late in the day, and reduced serotonin (which also improves reproduction) which reduce CYP1B1 for lower estrogen signaling.
Low estrogen signaling and higher androgen signaling leads to lower allopregnanolone.
With lower estrogen signaling there would be selection pressure elsewhere to compensate such as in the brain where walking down the list of genetic variants related to intelligence we see today, many simply compensate for weaker estrogen signaling.
The poor cortisol response, low serotonin response, high progesterone, low estrogen, and low allopregnanolone is the formula for enhancement abilities to detect unexpected events.
Low cortisol can increase sugar cravings. Evolutionary pressures would then favored a behavioral shift and somewhere between 130-70,000 years ago we know Neanderthals started eating more starchy foods such as grains which were also calorie dense. This dietary shift to more sugary foods also meant more calories, more stable survival, and eventually, less need to rely on cannibalism (yes, the bones and teeth marks don’t lie).
The Neanderthal cave art was a storage medium for animal reproduction cycles. This demonstrates a new skill: proactive, long-term cognitive modeling, something that also had to be learned and taught for growing grain which takes seasons.
Neanderthals began to interbreed. Neanderthal mitochondrial DNA faded out (the lower female fertility associated with NCAH certainly didn’t help), but male Neanderthal genes mixed in successfully. While much of the DNA was spread out or lost, the most valuable roughly 2–4% of the DNA, everything around the HPA Axis is seen together and can be found in many humans today.
The last glacial period (the Younger Dryas) forced the Neanderthal/Human decedents southward in what is today Europe. The megafauna extinction combined with the sudden rise in population created the ideal demographic conditions to catalyze systemic farming which led to permanent settlements (by a population that had an immune system that could handle it) in places like Mesopotamia but also in places like China where they also grew a starch (rice). Agricultural societies then spread and with them, the Neanderthal derived genetic quirks that helped shape modern humanity.