Mutation Linked to Difference Between Human and Neanderthal Brains
Even though modern humans are highly similar to our ancient Neanderthal cousins, there are some key differences between us—most notably, more neuron-packed frontal lobes. Now, researchers have identified a possible genetic trigger that led to increased neuron production in that brain region, which is associated with higher-level cognition as well as impulse control and emotional regulation: a mutation that ultimately alters metabolism in cells that become neurons.
The research, published yesterday (September 8) in Science, finds that the modern human and the archaic Neanderthal versions of the gene that codes for the protein transketolase-like 1 (TKTL1) differ by just one base pair. That point mutation in TKTL1 means that the Neanderthal version of the protein has a lysine where the modern human version has an arginine. After conducting experiments with fetal human neocortex tissue, mouse and ferret models, and engineered human brain organoids, the researchers behind the study conclude that the mutated gene’s behavior may explain humanity’s neuron-rich brains and could point to humans having a higher intellect than Neanderthals.
The study is unique and particularly well-executed, says Carol Marchetto, a neural evolution researcher at the University of California, San Diego, who didn’t work on the study. “What is quite amazing is that it’s only one amino acid substitution that can make a lot of change. . . . I find it really fascinating when this happens. We’re not even talking about knocking out or knocking down the gene.”
What the experiments collectively show is that the solitary lysine-to-arginine substitution in TKTL1 leads to an increase in the production of basal radial glia—neural progenitor cells that, during embryonic development, divide asymmetrically to produce more of themselves as well as most of the neurons in the frontal lobes. Having more of these glia in turn resulted in more neurons developing in the area. While there aren’t any Neanderthals around to recruit for cognitive tests, experts tell The Scientist that the increased neuron count in modern human brains could indicate that our subspecies developed greater cognitive abilities, though the relative intelligence of humans and Neanderthals is subject to substantial debate.
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