Creationism In Crisis - Modern Humans Were Cleverer Than Neanderthals Because of a Small Mutation in a Single Gene

Microscopy picture of a dividing basal radial glial cell, a progenitor cell type that generates neurons during brain development. Modern human TKTL1, but not Neandertal TKTL1, increases basal radial glia and neuron abundance.

© Pinson et al., Science 2022 / MPI-CBG

Modern humans generate more brain neurons than Neandertals: MPI-CBG

The scientifically nonsensical claim, often parroted by Creationists, is that all mutations are deleterious, therefore mutations can't be the basis for evolution. Although still pretending Creationism is science, following the repeated failure to convince a court of that, the reason Creationists give for that idiotic view of mutations is because, so their favourite myths say, all life was created magically and perfect by a perfect creator, so any change from that initial perfection must be imperfect in some way, and this was only possible because of 'The Fall'.

In other words, the dogma is barely disguised fundamentalist religion, plain and simple, and ignores the fact that many mutations are demonstrably advantageous and came to predominate in the species gene pool for that reason. There is of course, no mechanism by which a deleterious mutation can accumulate in the gene pool, let alone become fixed in the species, unless it rides on the back of a much more advantageous mutation in an associated gene.

And now a team of scientists from the Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany, have discovered that a single mutation in a single gene could have given modern humans the intellectual edge over Neanderthals, and probably other archaic hominins. It will take considerable mental gymnastics for the frauds to present that as supporting Creationism to their cult.

The mutation was a single nucleotide change in the gene which changed a codon from that for the amino acid, lysine in Neanderthals, to that for arginine in modern humans. The research team have shown that this small change in the resulting protein, means modern humans have many more neurones in their brain, especially in the frontal region, which is responsible for cognition. This may have meant moderns were quicker to learn and generally more intelligent than Neanderthals.

The news release from the Max Planck Institute explains the research and the significance of this discovery:

The question of what makes modern humans unique has long been a driving force for researchers. Comparisons with our closest relatives, the Neandertals, therefore provide fascinating insights. The increase in brain size, and in neuron production during brain development, are considered to be major factors for the increased cognitive abilities that occurred during human evolution. However, while both Neandertals and modern humans develop brains of similar size, very little is known about whether modern human and Neandertal brains may have differed in terms of their neuron production during development. Researchers from the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden now show that the modern human variant of the protein TKTL1, which differs by only a single amino acid from the Neandertal variant, increases one type of brain progenitor cells, called basal radial glia, in the modern human brain. Basal radial glial cells generate the majority of the neurons in the developing neocortex, a part of the brain that is crucial for many cognitive abilities. As TKTL1 activity is particularly high in the frontal lobe of the fetal human brain, the researchers conclude that this single human-specific amino acid substitution in TKTL1 underlies a greater neuron production in the developing frontal lobe of the neocortex in modern humans than Neandertals.

Only a small number of proteins have differences in the sequence of their amino acids – the building blocks of proteins – between modern humans and our extinct relatives, the Neandertals and Denisovans. The biological significance of these differences for the development of the modern human brain is largely unknown. In fact, both, modern humans and Neandertals, feature a brain, and notably a neocortex, of similar size, but whether this similar neocortex size implies a similar number of neurons remains unclear. The latest study of the research group of Wieland Huttner, one of the founding directors of the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, carried out in collaboration with Svante Pääbo, director at the Max Planck Institute for Evolutionary Anthropology in Leipzig, and Pauline Wimberger of the University Hospital Dresden and their colleagues, addresses just this question. The researchers focus on one of these proteins that presents a single amino acid change in essentially all modern humans compared to Neandertals, the protein transketolase-like 1 (TKTL1). Specifically, in modern humans TKTL1 contains an arginine at the sequence position in question, whereas in Neandertal TKTL1 it is the related amino acid lysine. In the fetal human neocortex, TKTL1 is found in neocortical progenitor cells, the cells from which all cortical neurons derive. Notably, the level of TKTL1 is highest in the progenitor cells of the frontal lobe.

Modern human TKTL1, but not Neandertal TKTL1, leads to more neurons in embryonic mouse neocortex
Anneline Pinson, the lead author of the study and researcher in the group of Wieland Huttner, set out to investigate the significance of this one amino acid change for neocortex development. Anneline and her colleagues introduced either the modern human or the Neandertal variant of TKTL1 into the neocortex of mouse embryos. They observed that basal radial glial cells, the type of neocortical progenitors thought to be the driving force for a bigger brain, increased with the modern human variant of TKTL1 but not with the Neandertal variant. As a consequence, the brains of mouse embryos with the modern human TKTL1 contained more neurons.

More neurons in the frontal lobe of modern humans

We found that with the Neandertal-type of amino acid in TKTL1, fewer basal radial glial cells were produced than with the modern human-type and, as a consequence, also fewer neurons. This shows us that even though we do not know how many neurons the Neandertal brain had, we can assume that modern humans have more neurons in the frontal lobe of the brain, where TKTL1 activity is highest, than Neandertals.

Anneline Pinson, first author
Max Planck Institute of Molecular Cell Biology and Genetics
Dresden, Germany.

This study implies that the production of neurons in the neocortex during fetal development is greater in modern humans than it was in Neandertals, in particular in the frontal lobe. It is tempting to speculate that this promoted modern human cognitive abilities associated with the frontal lobe.

Professor Wieland Huttner, corresponding author
Max Planck Institute of Molecular Cell Biology and Genetics
Dresden, Germany.

After this, the researchers explored the relevance of these effects for human brain development. To this end, they replaced the arginine in modern human TKTL1 with the lysine characteristic of Neandertal TKTL1, using human brain organoids – miniature organ-like structures that can be grown from human stem cells in cell culture dishes in the lab and that mimic aspects of early human brain development.

The researchers also found that modern human TKTL1 acts through changes in metabolism, specifically a stimulation of the pentose phosphate pathway followed by increased fatty acid synthesis. In this way, modern human TKTL1 is thought to increase the synthesis of certain membrane lipids needed to generate the long process of basal radial glial cells that stimulates their proliferation and, therefore, to increase neuron production.

The team give more details in the structured abstract to their paper published in Science:

Structured Abstract

INTRODUCTION

The evolutionary expansion of the neocortex and the concomitant increase in neuron production are considered to be a basis for the increase in cognitive abilities that occurred during human evolution. Endocast analyses reveal that the endocranial volume of modern humans and Neanderthals was similar, suggesting similar brain and neocortex size. But whether similar neocortex size implies similar neocortical neuron production remains unclear.

RATIONALE

Transketolase-like 1 (TKTL1) is a gene from the transketolase family that in fetal human neocortex is preferentially expressed in the two classes of neuroprogenitors, the apical progenitors in the ventricular zone and the basal progenitors in the subventricular zone. The latter class of neuroprogenitors comprises two major types, the basal intermediate progenitors (bIPs) and the basal radial glia (bRG, also called outer radial glia). bRG exhibit cellular processes that promote their ability to self-amplify, and are the neuroprogenitor type considered to be a driver of the increase in cortical neuron production, which is a hallmark of the evolution of the human neocortex. Reflecting their cell polarity, bRG undergo repeated asymmetric divisions that self-renew the bRG and generate one neuron each. Thereby, bRG generate more neurons over time than the other type of neuron-generating basal neuroprogenitors, the process-lacking bIPs whose neurogenic divisions are symmetric self-consuming. TKTL1 is one of the few proteins with a single amino acid substitution found in essentially all present-day humans but absent from extinct archaic humans, the Neanderthals and Denisovans, and other primates. This human-specific amino acid substitution in TKTL1 is a lysine in apes and archaic humans but an arginine in modern humans. We therefore investigated (i) whether TKTL1 has a role in neocortex development and affects neuroprogenitor numbers and (ii) whether both archaic TKTL1 (aTKTL1) and modern human TKTL1 (hTKTL1) exert similar effects on neuroprogenitors during neocortex development.

RESULTS

When expressed in mouse embryo neocortex, which lacks TKTL1 expression, hTKTL1 increased the abundance of bRG without affecting that of bIPs and that of apical progenitors. The effect of TKTL1 on bRG abundance was limited to hTKTL1; aTKTL1, which differs only by one amino acid, was unable to increase bRG abundance. The greater bRG abundance upon hTKTL1 expression resulted in an increase in cortical neuron production over time, specifically of the late-born upper-layer neurons rather than of the early-born deep-layer neurons. In the folded (gyrencephalic) developing ferret neocortex, hTKTL1 expression increased not only bRG abundance but also the proportion of bRG with multiple processes, a hallmark of bRG that can self-amplify. As a consequence of this effect, gyrus size increased.

In fetal human neocortex, hTKTL1 was essential to maintain the full number of bRG, as CRISPR-Cas9–mediated hTKTL1 knockout in fetal human neocortical tissue reduced this number. To further demonstrate the relevance of this effect, we converted hTKTL1 to the Neanderthal variant aTKTL1 in human embryonic stem cells and generated minibrain structures called cerebral organoids. The aTKTL1-expressing organoids contained fewer bRG and neurons, hence the human-specific lysine-to-arginine substitution in hTKTL1 is essential for maintaining the full number of bRG and neurons in this human brain model. In fetal human neocortex, hTKTL1 expression in neuroprogenitors increased during the course of neurogenesis and was particularly high in the developing frontal lobe as compared to the developing occipital lobe.

As to its mechanism of action, hTKTL1 increased bRG abundance via two metabolic pathways, the pentose phosphate pathway (PPP) followed by fatty acid synthesis. Inhibition of the PPP or of fatty acid synthesis, using a variety of specific inhibitors, completely suppressed the hTKTL1-induced increase in bRG abundance in embryonic mouse neocortex and reduced bRG numbers in fetal human neocortical tissue. This metabolic action of hTKTL1, but not aTKTL1, in bRG resulted in an increase in the concentration of acetyl–coenzyme A, the critical metabolite for fatty acid synthesis. Our data suggest that hTKTL1, but not aTKTL1, promotes the synthesis of membrane lipids containing a certain type of fatty acid that are required for the outgrowth of bRG processes and hence for the increase in bRG abundance.

CONCLUSION In light of our finding that TKTL1 expression in fetal human neocortex is particularly high in the developing frontal lobe, our study implies that because of the single amino acid–based activity of hTKTL1, neocortical neurogenesis in modern humans was and is greater than it was in Neanderthals, in particular in the frontal lobe.

Graphical Abstract

TKTL1 and hominin cortical neurogenesis.
The single lysine-to-arginine substitution in modern human TKTL1 leads to greater bRG numbers than in Neanderthals. These bRG in turn generate more neocortical neurons in modern humans. Because TKTL1 expression in fetal human neocortex is particularly high in the developing frontal lobe, these findings imply that the frontal lobe of modern humans contains more neurons than that of Neanderthals.

Abstract

Neanderthal brains were similar in size to those of modern humans. We sought to investigate potential differences in neurogenesis during neocortex development. Modern human transketolase-like 1 (TKTL1) differs from Neanderthal TKTL1 by a lysine-to-arginine amino acid substitution. Using overexpression in developing mouse and ferret neocortex, knockout in fetal human neocortical tissue, and genome-edited cerebral organoids, we found that the modern human variant, hTKTL1, but not the Neanderthal variant, increases the abundance of basal radial glia (bRG) but not that of intermediate progenitors (bIPs). bRG generate more neocortical neurons than bIPs. The hTKTL1 effect requires the pentose phosphate pathway and fatty acid synthesis. Inhibition of these metabolic pathways reduces bRG abundance in fetal human neocortical tissue. Our data suggest that neocortical neurogenesis in modern humans differs from that in Neanderthals.

Pinson, Anneline; Xing, Lei; Namba, Takashi; Kalebic, Nereo; Peters, Jula; Oegema, Christina Eugster; Traikov, Sofia; Reppe, Katrin; Riesenberg, Stephan; Maricic, Tomislav; Derihaci, Razvan; Wimberger, Pauline; Pääbo, Svante; Huttner, Wieland B.
Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals
Science 2022 377(6611), eabl6422; doi: 10.1126/science.abl6422

Copyright © 2022 The Authors
Published by American Association for the Advancement of Science
Reprinted with kind permission under licence #5385050541233

One of the many hypotheses about why the Neanderthals disappeared soon after the arival of anatomically modern Homo sapiens in Eurasia is that we simply outsmarted them and so became the more successful competitors for territory and hunting. This finding adds weight to that hypothesis.

But the problem for Creationists is that this difference was due to a small mutation in a single codon in a single gene, so substituting one amino acid in a key protein for another. Yet their dogma states that all mutations are deleterious and 'devolutionary', to use Michael J Behe's latest attempt to give a semblance of scientific credence to Creationism, which has been met with almost universal derision in the scientific community.

I doubt that anyone in their right mind would call having intellectual superiority over rivals, 'deleterious' or would assume having greater intelligence is somehow 'devolution', but that is what Creationists are now required to believe. What we can expect therefore, is for Creationists to either ignore this finding altogether, to attack the scientists, to rubbish the science or dismiss the whole thing as 'scientism' or the work of 'Satanists' who hate God.

One way or another they will need to cope with the cognitive dissonance caused by their preferred view of reality being so different to actual reality as science reveals it. However, they are so used to that by now that it should be a matter of routine.

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