Small DNA changes separate chimp and human brains

From left to right, the structures of A-, B- and Z-DNA. Credit: Wikipedia

Modern humans share about 95 percent of their genetic code with chimpanzees. Yet human brains, and what we do with them, are vastly different.

In the decade since the human genome was mapped, researchers have identified hundreds of small regions that differ between humans and fellow primates. Many show evidence of accelerated changes that might offer evolutionary clues to such fundamental differences as skeletal structure, motor skills and cognition since our human ancestors parted ways with chimpanzees some 6 million years ago.

A new study suggests that just 10 differences on one particular strand of human DNA lying near a gene could have been instrumental in the explosive growth in the human neocortex.

The DNA region, containing just 1,200 base pairs, is not a gene. But it lies near one that is known to affect early of the human neocortex, according to the study, published online this week in Current Biology.

Researchers showed that the region, known as HARE5, acts as an enhancer of the gene FZD8. Embryos of mice altered with human HARE5 developed significantly larger brains and more neurons compared with embryos carrying the chimp version, according to the study.

"It could contribute to making us unique, and making our brains unique," said Duke University developmental neuroscientist Debra Silver, co-author of Thursday's study. "We're seeing the human enhancer turn on gene activity right at the onset of when a population of cells called are rapidly proliferating. They shift within a day or two to making neurons."

The type of neurons and the timing of their development are significant - these excitatory neurons arise later in utero, which is consistent with human fetal brain development patterns driven by the gene in question.

So have they found the genetic missing link between chimp brains and ?

"We think it's likely that there's many additional accelerated regions that are contributing to human brain development, and they may be impacting other aspects that make our brains unique," Silver said.

"It still would be a pretty big gap to go all the way to: 'Oh, and that's why we have a spoken language, or different types of fine muscle movements or different cognitive abilities,'" said Katherine Pollard, an evolutionary genomics researcher at the University of California, San Francisco's Gladstone Institutes, who was not involved in the study. "But this is certainly a big step in that direction."

Pollard conducted early research that identified many regions of the that appear to be evolving fast.

"Almost all of these sequences were outside of genes and in most cases had no annotated function," Pollard said. "Nobody had ever considered that genome sequence before or studied them in any way."

Pollard's lab and others have been trying to fill in those gaps.

"This paper is part of that growing body of work," Pollard said. "What's particularly exciting about it is that it goes a little bit further than just saying this particular sequence functions as a regulatory enhancer, and tries to get at the question of what would be the molecular- or ultimately organismal-level trait associated with the changes in the DNA."

The full-grown mice with the larger brains are still around, and Silver's lab will be trying to devise ways to test whether they show behavioral differences attributable to the brain changes.

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Journal information: Current Biology

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Feb 21, 2015
Excerpt: "...containing just 1,200 base pairs, is not a gene. But it lies near one that is known to affect early development of the human neocortex..."

A single base pair linked to a nutrient-dependent amino acid substitution also links several different morphological characteristics in mice to a modern human population that adapted to ecological variation in what is now central China during the past ~30K years.

The link from the epigenetic landscape to the physical landscape of DNA in the organized genomes of both species was also reported in the context of mutations across millions of years.

Dobzhansky (1973) attributed some differences in primates to a single amino acid substitution. "...the so-called alpha chains of hemoglobin have identical sequences of amino acids in man and the chimpanzee, but they differ in a single amino acid (out of 141) in the gorilla."

Does anyone know how long it takes for one amino acid to cause a global change in phenotype?

Feb 21, 2015
Sounds like it would be relatively easy to tweek a chimp brain. I think we should do it. For science.

Feb 21, 2015
"Embryos of mice altered with human HARE5 developed significantly larger brains...The full-grown mice with the larger brains are still around... "

And people are worried about genetically engineered corn getting out of the lab?

Feb 21, 2015
Sounds like it would be relatively easy to tweek a chimp brain. I think we should do it. For science.

Dr. Zaius would approve.

Feb 22, 2015
Sounds like it would be relatively easy to tweek a chimp brain. I think we should do it. For science.

Dr. Zaius would approve.
Ever read Heinleins 'Time Enough for Love'? Lazarus Longs talking mule? Everything that can be done eventually will be done. Most likely.

Feb 22, 2015
http://www.ncbi.n...24693349 Excerpt: "Conditioned hormonal and behavioral responses to odors associated with food selection and conspecifics in mammals require something like the collective 'neural networks' of beehives. Philosophically and metaphorically, these neural networks extend to mammalian brains. The concept that is extended is the epigenetic tweaking of immense gene networks in 'superorganisms' (Lockett, Kucharski, & Maleszka, 2012) that 'solve problems through the exchange and the selective cancellation and modification of signals (Bear, 2004, p. 330)'. It is now clearer how an environmental drive probably evolved from that of food ingestion in unicellular organisms to that of socialization in insects."

Why can't others grasp the facts about how ecological variation leads to ecological adaptations in species from microbes to man? I cite Dobzhansky (1973); I cite my reviews, and no one seems to become biologically informed.

Feb 27, 2015
very interesting, metaphysically, I used to wonder on atomic structure scattering materials here and there, so many elements are made, so do these structures as I see and abstract make so many differences, as I see them the colour bands and the sinusoidal curve twist, the bands in-between resemble the frequency bars and I have belief these identify themselves through resonance with varying bar length, lumped mass distribution, sorry, just to add my odd thoughts...

Feb 27, 2015
This does not need to be viewed metaphysically.

See: Molecular Vibration-Sensing Component in Human Olfaction

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