The 'smart gene' that Determines victory

Neanderthals, our closest relatives to modern Homo sapiens, split up about half a million years ago. Since then, they have migrated out of Africa and crossed paths and even exchanged genes in Eurasia. In the end, modern Homo sapiens won the battle for survival, while Neanderthals were eliminated.

Anthropologists generally believe that Neanderthals were outsmarted. The problem is, archaeological evidence suggests that Neanderthals' brains were about the same size as those of modern Homo sapiens. If they weren't smart, it would have to be the number of neurons or the structure of the brain. Unfortunately, there is no way to study this difference by analyzing fossilized skulls.

In 2010, the Max Planck Institute for Evolutionary Anthropology in Germany shocked the world by sequencing the entire genome of Neanderthals. Preliminary analyses suggest that the genomes of Neanderthals and modern Homo sapiens differ by only 1.2 parts per thousand, or 1.2 nucleotides per thousand. The genetic difference between any two modern Homo sapiens is known to be 1 in 1,000, so Neanderthals and modern Homo sapiens are fairly closely related.

Further analysis revealed THAT THERE WERE more than 30, 000 meaningful differences between the two genomes, most of them in gene regulatory segments, with only 96 differences actually affecting the coding of amino acids. In other words, if you broke down the bodies of modern Homo sapiens and Neanderthals into proteins and measured the amino acid sequence of those proteins, you would find only 96 differences.

These 96 differences may well account for subtle differences in height, weight, skin color, appearance, and so on, but it's the brain that most people care about. Researchers at the Max Planck Institute took a closer look at the 96 amino acid proteins and concluded that one of them, called transketonase-like protein-1, or TKTL1, was most likely involved in brain neural development.

Specifically, the protein is involved in the development and growth of neuronal precursor cells, especially in the development of the Neocortex, which determines intelligence. The modern Homo sapiens version of TKTL1 has an arginine in that position, whereas the Neanderthal version of TKTL1 has a lysine in that position.

What effect would such a small difference have on neural development? Dr. Anneline Pinson, a neurobiologist at the institute, took up the challenge. First, she and her colleagues used gene-editing technology to insert the modern Homo sapiens and Neanderthal versions of the TKTL1 gene into the genomes of mouse embryos and then let them continue to develop. They found that the brains of mice implanted with the modern Homo sapiens version had more neuronal precursor cells.

Again next, the researchers through gene editing techniques have replaced TKTL1 protein in modern homo sapiens stem cells with a Neanderthal version, it is found that the transferred the stem cells produced a number of Neanderthal genes less of neuronal precursor cells, which further shows that neanderthals TKTL1 version has adverse effects on the neural development.

Finally, and most crucial, is the experiment with so-called mini-brains. The researchers grew the stem cells of modern Homo sapiens into a three-dimensional mass of neurons that best mimics the development of brain tissue. The researchers then repeated the experiment using gene-editing technology to replace the human version of TKTL1 with the Neanderthal version, again proving that the human version was superior.

Dr Pinatsu published his findings in a paper in the September 9, 2022 issue of the journal Science. This is of course only a preliminary experiment, which needs to be verified by further studies. But the results suggest that a seemingly innocuous, random genetic mutation may have radically altered the pattern of neural development in the brain, giving modern Homo sapiens the intellectual edge to be the winners.