What makes humans smarter than chimps?

Why have geneticists considered complete sequencing of the genomes of a variety of species so important? One reason (of many) is what we learn by comparing these other genomes with the human genome. And if you consider the genome of a close relative of humans, such as our closest relatives, chimpanzees, the comparison may be particularly enlightening.

The complete sequencing of the chimp genome was announced in August 2005. In May of this year, some results from comparing human and chimp genomes started to emerge:

Chimpanzee study reveals genome variation hotspots

Researchers believe that dynamic regions of the human genome - "hotspots" in terms of duplications and deletions - are potentially involved in the rapid evolution of morphological and behavioral characteristics that are genetically determined.

Now, an international team of researchers, including a graduate student and an associate professor from Arizona State University, are finding similar hotspots in chimpanzees, which has implications for the understanding of genomic evolution in all species.

That's an interesting clue, but it still doesn't tell us much about what accounts for the difference between human and chimp brains. More specifics about this came out three months ago, in August:

Scientists Find Brain Evolution Gene

Scientists believe they have found a key gene that helped the human brain evolve from our chimp-like ancestors. In just a few million years, one area of the human genome seems to have evolved about 70 times faster than the rest of our genetic code. It appears to have a role in a rapid tripling of the size of the brain's crucial cerebral cortex, according to an article published Thursday in the journal Nature.

Study co-author David Haussler, director of the Center for Biomolecular Science and Engineering at the University of California, Santa Cruz, said his team found strong but still circumstantial evidence that a certain gene, called HAR1F, may provide an important answer to the question: "What makes humans brainier than other primates?" Human brains are triple the size of chimp brains.

But that's only the beginning of the story:

Scientists Identify Gene Difference Between Humans and Chimps

Although this research does not definitively link this region to brain differences between humans and our closest relatives, it is intriguing. "We don't know what it does, and we don't know if it interacts with reelin, but the evidence is very suggestive that this gene is important in the development of the cerebral cortex, and that's exciting because the human cortex is three times as large as it was in our predecessors," notes team leader David Haussler of the University of California, Santa Cruz. "Something caused our brains to evolve to be much larger and have more function than the brains of other mammals."

And, of course, this is just the first of the 49 rapidly evolving regions to be studied. "Now we have to go through the other 48," Haussler says.

Sure enough, other interesting things are being found in other regions of the human genome that have evolved rapidly. This came out in October:

DNA trail points to human brain evolution

The human brain may have evolved beyond that of our primate cousins because our brain cells are better at sticking in place, researchers say.

A new study comparing the genomes of humans, chimps, monkeys and mice found an unexpectedly high degree of genetic difference in the human DNA regions that influence nerve cell adhesion, compared with the DNA of the other animals.

Accelerated evolution here allowed human brain cell connections to form with greater complexity, enabling us to grow bigger brains, the researchers suggest.

Ah ha. So enhanced adhesion between neurons facilitates bigger brains. That makes sense. But the story gets even more interesting, because apparently it's not only specific genes that play a role in this, but certain noncoding DNA regions between genes do also:

Looking for Smarts Between the Genes

The strongest evidence for accelerated evolution on the human line was found in noncoding sequences next to genes involved in helping neurons adhere to each other. The team found 69 such sequences, suggesting that changes in these regulatory elements may have contributed to the evolution of uniquely human cognitive talents.

Neuronal adhesion molecules play a major role in wiring the brain, Rubin says, such as the formation of connective synapses between nerve cells. These processes, he adds, are important in early brain development and also crucial for learning, memory, and cognition in adults. For example, Rubin says, one of the noncoding sequences is next to a gene called CNTN4, which appears to be involved in the development of both verbal and nonverbal communication abilities in humans, while another is adjacent to CHL1, which is linked to cognition in both humans and mice.

So this links up with another famously intriguing question: why is it that more than 90% of the human genome is made up of gaps between genes, gaps that don't seem to code for any proteins? Researchers have begun to suspect that some of this noncoding DNA consists of regulatory sequences that can affect, in different ways, when different genes are "expressed" and actually able to produce specific proteins. Looks like some of this noncoding DNA is important enough to help account for the rapid evolution of human brains.

I have the feeling we're just seeing the beginning of research findings in this area, and we're about to be hit by an avalanche of it. Here's another study reported just this week. It involves not just single genes, but entire networks of interconnected genes:

Unraveling where chimp and human brains diverge

By evaluating the correlated activity of thousands of genes, the UCLA team identified not just individual genes, but entire networks of interconnected genes whose expression patterns within the brains of humans varied from those in the chimpanzee.

"Genes don't operate in isolation – each functions within a system of related genes," said first author Michael Oldham, UCLA genetics researcher. "If we examined each gene individually, it would be similar to reading every fifth word in a paragraph – you don't get to see how each word relates to the other. So instead we used a systems biology approach to study each gene within its context."

The scientists identified networks of genes that correspond to specific brain regions. When they compared these networks between humans and chimps, they found that the gene networks differed the most widely in the cerebral cortex -- the brain's most highly evolved region, which is three times larger in humans than chimps.

Secondly, the researchers discovered that many of the genes that play a central role in cerebral cortex networks in humans, but not in the chimpanzee, also show significant changes at the DNA level.

Since there are probably scores of genes implicated in human-chimp brain differences, organized in different networks, I expect we're going to see research on this come out for some time to come.


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Additional information:

Accelerated Evolution of Conserved Noncoding Sequences in Humans

This is the abstract of the article in Science which describes the research about the importance of noncoding DNA for human brain evolution. (Subscription rqd for access to full text of the article.)

Scientists Explore Function of 'Junk DNA'

Via Evolution Research, this is a recent (like, last two days) news item on research into noncoding DNA that works by coding for microRNA.

Tags: biology, neuroscience, human evolution, noncoding DNA