Key Differences Revealed Between Brains of Modern Humans and Neanderthals

What distinguishes the modern human being? Researchers have long been motivated by this question. Comparing us to our nearest cousins, the Neanderthals, so reveals fascinating insights. It is believed that the fundamental causes of the enhanced cognitive capacities that happened during human evolution were a rise in brain size and an increase in neuron creation during brain growth. Although the brains of contemporary humans and Neanderthals grow to be around the same size, nothing is known about whether the creation of neurons in the two species' respective brains varied during development.

A basal radial glial cell, a type of progenitor cell that produces neurons during brain development, is shown in a microscopy image as it is dividing. The abundance of basal radial glia and neurons is increased by modern human TKTL1, but not by Neanderthal TKTL1. Science 2022/MPI-CBG/Pinson et al.

Researchers from the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden have found that the modern human variant of the protein TKTL1, which differs from the Neanderthal variant by just one amino acid, causes an increase in a particular type of brain progenitor cells known as basal radial glia. The bulk of neurons are produced by basal radial glial cells in the growing neocortex, an area of the brain that is crucial for many cognitive functions. The researchers come to the conclusion that this one human-specific amino acid substitution in TKTL1 is responsible for a higher neuron production in the developing frontal lobe of the neocortex in modern humans than in Neanderthals because TKTL1 activity is particularly high in the frontal lobe of the fetal human brain.

Between modern humans and our lost ancestors, the Neanderthals and Denisovans, only a small number of proteins differ in the sequence of their amino acids, which are the building blocks of proteins. How these variations affected the evolution of the contemporary human brain is mainly unknown from a scientific perspective. In fact, the brains of modern humans and Neanderthals are similar in size, particularly the neocortex, albeit it is unclear if this similarity in neocortex size means a similar number of neurons.

One of the founding directors of the Dresden-based Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Wieland Huttner's research team has now released a study that specifically addresses this issue. The Max Planck Institute for Evolutionary Anthropology's Svante Pääbo, Pauline Wimberger of the University Hospital Dresden, and their associates participated in the research project.

The protein transketolase-like 1 is the one that the researchers are concentrating on because it differs from Neanderthals by a single amino acid in virtually all contemporary humans (TKTL1). The sequence location in question in TKTL1 in modern humans has an arginine, whereas in TKTL1 from Neanderthals, the similar amino acid lysine is present. Neocortical progenitor cells—from which all cortical neurons develop—are detected in the fetal human neocortex and contain the gene TKTL1. The progenitor cells of the frontal lobe are notable for having the greatest amount of TKTL1.

There are more neurons in the developing mouse neocortex when modern human TKTL1 is present but not Neanderthal TKTL1.

The purpose of this study was to determine the importance of this single amino acid alteration for neocortex development, according to Wieland Huttner's lab member and study lead author Anneline Pinson. In the neocortex of mouse embryos, Anneline and her colleagues either inserted the Neanderthal or the current human form of TKTL1. They discovered that the modern human variety of TKTL1 boosted basal radial glial cells, the kind of neocortical progenitors thought to be the catalyst for a larger brain, but not the Neanderthal variant. The result was that mouse embryos carrying the modern human TKTL1 had more neurons in their brains.

The frontal lobe of contemporary people has more neurons.

The relevance of these impacts to human brain development was then investigated by the researchers. With the help of human brain organoids, they achieved this by swapping out the arginine present in modern human TKTL1 with the lysine present in Neanderthal TKTL1. In a laboratory setting, these tiny organ-like structures that resemble the early stages of the human brain can be created using human stem cells.

According to Anneline Pinson, "We found that basal radial glial cells and neurons were both decreased when the Neanderthal-type of amino acid in TKTL1 was used as compared to the present human-type. "This demonstrates that even though we do not know how many neurons the Neanderthal brain contained, we may assume that modern humans have more neurons in the frontal lobe of the brain, where TKTL1 activity is highest, than Neanderthals."

Additionally, the scientists found that the current human TKTL1 affects metabolism. the stimulation of the pentose phosphate pathway, which is followed by an increase in the production of fatty acids. In this manner, it is hypothesized that modern human TKTL1 promotes the synthesis of specific membrane lipids required to produce the protracted process of basal radial glial cells that drives their proliferation and, as a result, boosts neuron creation.

Wieland Huttner, the study's principal investigator, states that the findings "indicate that modern humans produce more neurons in the neocortex during fetal development than did Neanderthals, particularly in the frontal lobe." The frontal lobe-related cognitive capacities of modern humans may have been enhanced as a result, according to the enticing theory.

By MAX PLANCK INSTITUTE OF MOLECULAR CELL BIOLOGY AND GENETICS (MPI-CBG)