[Scientists have discovered a mutation that increases the
production of brain cells and seems to have set our ancestors apart
from other hominins.]
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WHAT MAKES YOUR BRAIN DIFFERENT FROM A NEANDERTHAL’S?  
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Carl Zimmer
September 8, 2022
New York Times
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_ Scientists have discovered a mutation that increases the production
of brain cells and seems to have set our ancestors apart from other
hominins. _

Paleoanthropologists have found that the brains of our ancestors
increased in size starting about two million years ago. , Javier
Trueba/MSF, via Science Source

 

Scientists have discovered a glitch in our DNA that may have helped
set the minds of our ancestors apart from those of Neanderthals and
other extinct relatives.

The mutation, which arose in the past few hundred thousand years,
spurs the development of more neurons in the part of the brain that we
use for our most complex forms of thought, according to a new study
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Science on Thursday.

“What we found is one gene that certainly contributes to making us
human,” said Wieland Huttner, a neuroscientist at the Max Planck
Institute of Molecular Cell Biology and Genetics in Dresden, Germany,
and one of the authors of the study.

The human brain allows us to do things that other living species
cannot, such as using full-blown language and making complicated plans
for the future. For decades, scientists have been comparing the
anatomy of our brain to that of other mammals to understand how those
sophisticated faculties evolved.

The most obvious feature of the human brain is its size — four times
as large as that of chimpanzees, our closest living relatives.

Our brain also has distinctive anatomical features. The region of the
cortex just behind our eyes, known as the frontal lobe, is essential
for some of our most complex thoughts. According to a study from 2018
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lobe has far more neurons than the same region in chimpanzees does.

But comparing humans with living apes has a serious shortcoming: Our
most recent common ancestor with chimpanzees lived roughly seven
million years ago. To fill in what happened since then, scientists
have had to resort to fossils of our more recent ancestors, known as
hominins.

Inspecting hominin skulls, paleoanthropologists have found that the
brains of our ancestors dramatically increased
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starting about two million years ago. They reached the size of living
humans by about 600,000 years ago. Neanderthals, among our closest
extinct hominin relatives, had brains as big as ours.

But Neanderthal brains were elongated, whereas humans have a more
spherical shape
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Scientists can’t say what accounts for those differences. One
possibility is that various regions of our ancestors’ brains changed
size.

An M.R.I. of a human brain with the frontal lobe
highlighted.Credit...Living Art Enterprises/Science Source

In recent years, neuroscientists have begun investigating ancient
brains with a new source of information: bits of DNA preserved inside
hominin fossils. Geneticists have reconstructed entire genomes
of Neanderthals
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well as their eastern cousins, the Denisovans
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Scientists have zeroed in on potentially crucial differences between
our genome and the genomes of Neanderthals and Denisovans. Human DNA
contains about 19,000 genes. The proteins encoded by those genes are
mostly identical to those of Neanderthals and Denisovans. But
researchers have found 96 human-specific mutations that changed the
structure of a protein.

In 2017, Anneline Pinson, a researcher in Dr. Huttner’s lab, was
looking over that list of mutations and noticed one that altered a
gene called TKTL1. Scientists have known that TKTL1 becomes active in
the developing human cortex, especially in the frontal lobe.

“We know that the frontal lobe is important for cognitive
functions,” Dr. Pinson said. “So that was a good hint that it
could be an interesting candidate.”

Dr. Pinson and her colleagues did initial experiments with TKTL1 in
mice and ferrets. After injecting the human version of the gene into
the developing brains of the animals, they found that it caused both
the mice and ferrets to make more neurons.

Next, the researchers carried out experiments on human cells, using
bits of fetal brain tissue obtained through the consent of women who
had abortions at a Dresden hospital. Dr. Pinson used molecular
scissors
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snip out the TKTL1 gene from the cells in the tissue samples. Without
it, the human brain tissue produced fewer so-called progenitor cells
that give rise to neurons.

For their final experiment, the researchers set out to create
a miniature Neanderthal-like brain
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They started with a human embryonic stem cell, editing its TKTL1 gene
so that it no longer had the human mutation. It instead carried the
mutation found in our relatives, including Neanderthals, chimpanzees
and other mammals.

They then put the stem cell in a bath of chemicals that coaxed it to
turn into a clump of developing brain tissue, called a brain organoid.
It generated progenitor brain cells, which then produced a miniature
cortex made of layers of neurons.

The Neanderthal-like brain organoid made fewer neurons than did
organoids with the human version of TKTL1. That suggests that when the
TKTL1 gene mutated, our ancestors could produce extra neurons in the
frontal lobe. While this change did not increase the overall size of
our brain, it might have reorganized its wiring.

“This is really a tour de force,” said Laurent Nguyen, a
neuroscientist at the University of Liège in Belgium who was not
involved in the study. “It’s remarkable that such a small change
has such a dramatic effect on the production of neurons.”

The new finding does not mean that TKTL1, on its own, offers the
secret to what makes us human. Other researchers are also looking at
the list of 96 protein-changing mutations and are running organoid
experiments of their own.

Other members of Dr. Huttner’s lab reported in July
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other mutations change the pace at which developing brain cells
divide. Last year
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a team of researchers at the University of California San Diego found
that another mutation appears to change the number of connections
human neurons make with each other.

Other mutations may also turn out to be important to our brains. For
example, as the cortex develops, individual neurons need to migrate in
order to find their proper place. Dr. Nguyen observed that some of the
96 mutations unique to humans altered genes that are likely involved
in cell migration. He speculates that our mutations may make our
neurons move differently than neurons in a Neanderthal’s brain.

“I don’t think it’s the end of the story,” he said. “I think
more work is needed to understand what makes us human in terms of
brain development.”

_CARL ZIMMER writes the “Matter”
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fourteen books, including “Life's Edge: The Search For What It Means
To Be Alive.” @carlzimmer
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* Science
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* neuroscience
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* human brain
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* anatomy
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* paleontology
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* Neanderthals
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* DNA
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* genes
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