A gene for brain size only found in humans

A gene for brain size only found in humans
This picture shows a cerebral cortex of an embryonic mouse. The cell nuclei are marked in blue and the deep-layer neurons in red. The human-specific gene ARHGAP11B was selectively expressed in the right half of the brain, which is visible by the folding of the neocortical surface. Credit: Molecular Cell Biology and Genetics

About 99 percent of human genes are shared with chimpanzees. Only the small remainder sets us apart. However, we have one important difference: The brain of humans is three times as big as the chimpanzee brain.

During evolution our genome must have changed in order to trigger such brain growth. Wieland Huttner, Director and Research Group Leader a the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), and his team identified for the first time a gene that is only present in humans and contributes to the reproduction of basal brain stem cells, triggering a folding of the neocortex. The researchers isolated different subpopulations of stem cells and precisely identified, which are active in which cell type. In doing so, they noticed the gene ARHGAP11B: it is only found in humans and in our closest relatives, the Neanderthals and Denisova-Humans, but not in chimpanzees. This gene manages to trigger brain stem cells to form a bigger pool of stem cells. In that way, during brain development more neurons can arise and the cerebrum can expand. The cerebrum is responsible for cognitive functions like speaking and thinking.

Wieland Huttner's researchers developed a method that isolates and identifies special subpopulations of brain stem cells from the developing human cerebrum. No one has managed to do this so far. The scientists first isolated different stem and progenitor cell types from fetal mice and human cerebrum tissue. In contrast to the big and folded human brain, the brain of mice is small and smooth. After the isolation, the researchers compared the genes that are active in the various cell types and were able to identify 56 genes that are only present in humans and which play a role in . "We noticed that the gene ARHGAP11B is especially active in basal brain stem cells. These cells are really important for the expansion of the neocortex during evolution," says Marta Florio, PhD student in Wieland Huttner's lab, who carried out the main part of the study.

The human-specific gene also works in mice

In the further course of the study, the researchers focused on the function of this special gene. The researchers suspected that if it was responsible for a bigger pool of brain stem cells in humans and thereby for an expanded cerebrum, then this human-specific gene should trigger a similar development in the smaller brain of a mouse. They introduced the gene into mice embryos and indeed: Under the influence of the human-specific gene, the mice produced significantly more brain and in half of all cases even a folding of the neocortex, which is typical for human brains. All these results suggest that the gene ARHGAP11B plays a key role in the evolutionary expansion of the human neocortex.

Data from researchers working with Svante Pääbo from the Max Planck Institute for Evolutionary Anthropology in Leipzig confirm that ARHGAP11B not only occurs in the human genome, but also existed in the Neanderthals and Denisova-Humans. Neanderthals had a similar big brain to humans. "ARHGAP11B is the first human-specific gene where we could show that it contributes to the pool of basal and can trigger a folding of the neocortex. In that way, we managed to take the next step in tracing evolution", summarizes Wieland Huttner.

His research group has been interested in the secrets of human brain evolution for a long time. In the last years, his researchers made several discoveries that contributed to the understanding of how a big brain could develop during evolution. In the year 2010 for example, the researchers identified a new type of stem cell in the outer growth zones of the brain.


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Small DNA changes separate chimp and human brains

More information: "Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion." Science DOI: 10.1126/science.aaa1975 Published Online February 26 2015
Journal information: Science

Provided by Max Planck Society
Citation: A gene for brain size only found in humans (2015, February 27) retrieved 25 May 2019 from https://medicalxpress.com/news/2015-02-gene-brain-size-humans.html
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JVK
Feb 27, 2015
http://www.scienc...abstract
Journal excerpt: "This indicates that the C-terminal 47 amino-acids of ARHGAP11B (after lysine-220) constitute not only a unique sequence, resulting from a frameshifting deletion (fig. S10), but also are functionally distinct from their counterpart in ARHGAP11A."

http://www.scienc...abstract
Journal excerpt: Genome resequencing revealed a single-nucleotide point mutation in ntrB in strain AR2S, causing an amino acid substitution within the PAS domain of the histidine kinase sensor NtrB [Thr97→Pro97 (T97P)] (13). The fast-spreading strain AR2F had acquired an additional point mutation in the σ54-dependent EBP gene ntrC, which alters an amino acid (R442C) within the DNA binding domain (Table 1 and table S2).

Pattern recognition suggests nutrient-dependent RNA-mediated amino acid substitutions cause cell type differentiation in all cells of all individuals of all species.

JVK
Feb 27, 2015
... we managed to take the next step in tracing evolution...


Co-author Svante Paabo took a bigger step towards tracing the nutrient-dependent RNA-mediated link from amino acid substitutions to primate brain development as senior author of "Natural Selection on the Olfactory Receptor Gene Family in Humans and Chimpanzees" http://linkinghub...07620138

Perhaps without knowing, Paabo linked viral microRNAs and nutrient-dependent microRNAs from the microRNA/messenger RNA balance to alternative splicings of pre-mRNAs and amino acid substitutions in enzymes. The substitutions link experience-dependent RNA-directed DNA methylation in microbes to their pheromone-controlled cell type differentiation and the de novo creation of olfactory receptor genes in primates. In all organisms, conserved molecular mechanisms link the biophysically constrained chemistry of nutrient-dependent protein folding to ecological adaptations.

Feb 28, 2015
Chimps could really do with a bigger brain in order to outwit each other in sexual competition. Their brains have reached a maximum. Any bigger and they overheat due to the configuration of the blood supply around the brain.
Pigs gave us an efficient blood cooling system for the brain.
In order to nail this thing to the wall we need to find porcine genes in humans and not in apes.
http://www.macroevolution.net

Feb 28, 2015
@Egleton

I hope your link was meant to evoke laughter.

Feb 28, 2015
Yes, of cause it was going to evoke laughter. Look at the reaction to Darwin's Origin of Species.
Laughter is the ape's "all clear" signal after some emergency.
Ho, Ho, Ho.

JVK
Feb 28, 2015
This is a great summary of what is currently known about nutrient-dependent RNA-mediated pheromone-controlled cell type differentiation in species from bio-luminescent gut microbes (in the bobtail squid) to all crustaceans and all insects and all marine mammals and all terrestrial mammals via the biophysically constrained chemistry of protein folding.

http://www.scienc...rc=email

Excerpt: "During RNA editing, specific enzymes alter nucleotides in mRNA transcripts so that the resulting protein differs in amino acid sequence from what was encoded by the original DNA. Such RNA editing is a means to generate greater protein diversity..."

Please ignore this if you are a theoretical physicist or evolutionary theorist who has been taught to believe in pseudoscientific nonsense. It is too late for you; this accurate information is for the next generation of serious scientists to consider.

Feb 28, 2015
Which evolutionary theorists deny RNA editing? It's a well known process we've known about since the 80's.

http://dna.kdna.u...ting.htm
http://en.wikiped..._editing

RNA editing, however, does not make changes to DNA. The substitutions resulting from RNA editing are not the same as substitutions resulting from DNA sequence changes.

JVK
Feb 28, 2015
What causes the DNA sequence changes?

Is there a model of biologically-based cause and effect that links them to cell type differences via what is currently known about physics, chemistry, and conserved molecular mechanisms that link the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man via RNA-mediated amino acid substitutions, which is what these authors did (including Svante Paabo -- of fossil record fame)?

http://www.scienc...abstract

Excerpt: "This indicates that the C-terminal 47 amino-acids of ARHGAP11B (after lysine-220) constitute not only a unique sequence, resulting from a frameshifting deletion (fig. S10), but also are functionally distinct from their counterpart in ARHGAP11A."


JVK
Feb 28, 2015
I also asked: "Is there a model of biologically-based cause and effect that links them to cell type differences via what is currently known about physics, chemistry, and conserved molecular mechanisms that link the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man via RNA-mediated amino acid substitutions, which is what these authors did (including Svante Paabo -- of fossil record fame)?"

Why don't you simply admit that you have no idea of how mutations lead to the evolution of increasing organismal complexity?

Mar 01, 2015
We are humans due to a mutant gene, that wasn't here before, magically, consistently, appearing in the monkey population, or earlier, creating the break between "us" and "them". Where and how do these genes pop into existence and cause constructive changes. What, randomness, "decides" this should take place. Could it be that out of 1000's of mutant genes that were dead ends one just happened to work. Trial and error evolution? If this is how all species differentiated, the creationists are beating a dead horse.

JVK
Mar 01, 2015
We are humans due to a mutant gene


Please cite the experimental evidence of biophysically constrained cause and effect that supports that ridiculous opinion and see:

Quantum Criticality at the Origin of Life http://arxiv.org/...02.06880

It links cell type differences via what is currently known about physics, chemistry, and conserved molecular mechanisms that link the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man via RNA-mediated amino acid substitutions, which is what these authors did (including Svante Paabo -- of fossil record fame)?"

I can picture Stuart A. Kaufmann politely trying to explain to Svante Paabo that he is a biologically uninformed science idiot, with the counter-claim by Paabo that "at least I got the part about olfaction right." I can also picture the anonymous fools who participate here trying to explain mutations lead from epigenesis to epistasis.

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