Scientists experimenting with mice have found evidence that key parts of the modern human brain take longer to develop than those of our long-lost cousin, the Neanderthals.
Like the hare and the tortoise, slow and steady is the winner here. The extra time is caused by protein differences that also appear to reduce chromosomal errors, ultimately resulting in a healthier, more robust population.
The study results imply that this stage in the development of our neocortex (the wrinkled outer layer responsible for higher-order thinking) plays a role in our protection against disease, a feature that Neanderthals seem to lack.
In recent years, advances in genetics have allowed scientists to sequence DNA extracted from ancient remains, revealing detailed information about how the Neanderthal genome compares and contrasts with our own.
We know, for example, about 100 amino acids – the compounds that make up proteins – that changed when modern humans diverged from the branch that gave rise to Neanderthals and another close cousin, the Denisovans.
Amino acid substitution can have significant effects, but it was unclear what functions these substitutions changed between humans and Neanderthals.
Six of the identified substitutions exist in proteins already known to play a role in chromosome distribution during cell division. So a team of researchers led by geneticist Felipe Mora-Bermúdez of the Max Planck Institute for Molecular Cell Biology and Genetics in Germany conducted experiments to see if they could determine the role these amino acid changes might play in the development of the neocortex.
The natural subject was laboratory mice, which share with Neanderthals (and monkeys) these same six amino acids in the relevant proteins. Using CRISPR Cas-9, the researchers replaced these amino acids with those found in modern humans.
They also took research in the opposite direction. They grew human brain organoids from embryonic stem cells – pieces of brain tissue that are neither alive nor sentient – and replaced modern human amino acids with the Neanderthal/mouse/monkey variants.
The results were startling and fascinating.
“We found that three modern human amino acids in two of the proteins cause a longer metaphase, a phase where the chromosomes are prepared for cell division,” Mora-Bermúdez explained, “and this leads to fewer errors when the chromosomes are distributed to daughter cells from neural stem cells, just as in modern humans.”
In addition, the metaphase of Neanderthalized human organoids was shorter, resulting in twice as many chromosome separation errors compared to control organoids. This suggests that three modern human amino acid substitutions are responsible for fewer chromosome distribution errors compared to Neanderthals.
Since errors in the number of chromosomes, called polysomies, can lead to serious disorders, as well as cancers such as leukemia and carcinoma, the findings suggest that the change has been to the benefit of modern humans. They also suggest that brain function in Neanderthals may have been affected by chromosomal disorders at a higher rate than seen in modern humans.
“Current data imply that the likelihood of such adverse effects of chromosome missegregation may be lower in modern humans than in Neanderthals, Denisovans, and apes,” the researchers wrote in their paper.
“Further work is needed to address the significance of these effects for the characteristic traits of modern humans.”
The research has been published in Science.