Al Fin: Human Brain Evolution: A Twisted Path to Greatness?

We know that something happened to the chimp:human brain, sometime after the paths of the two animals diverged. Probably several "somethings," as a matter of fact. Here is the curious story of one of those genetic tweaks that has helped make all the difference.

One Gene's Story

Gene duplications are rare in human history: only about 30 genes have copied themselves since we split from chimps 6 million years ago. Few have been studied, but those that have encode genes that are very exciting, says human geneticist Evan Eichler of the University of Washington in Seattle. Many are involved in brain development.

...Eichler and Franck Polleux of the Scripps Institute in La Jolla, California, chose to look at a duplicated gene called SRGAP2. It helps drive development of the neocortex, which controls higher-order brain functions such as language and conscious thought. Humans with mutations in this gene are prone to epileptic seizures, as are mice that have been engineered to lack it.

Eichler's group discovered that SRGAP2 duplicated itself 3.5 million years ago, well after humans and chimps diverged. One million years later, this "daughter" of the original gene underwent its own duplication and created a "granddaughter" copy. All three coexist in modern humans.

But just like a photograph of a photograph, as the duplications took place, each copy decreased in quality. The daughter and granddaughter genes were shorter than the original and weren't able to help the brain mature the way the original gene does. In fact, they did just the opposite: when Polleux and colleagues put human copies of the daughter and granddaughter genes into mice, the proteins they made bound to the original SRGAP2 and hindered its ability to do its job.

The effect of this genetic sabotage, however, was that the brain had more time to develop. Although the mouse's brain itself didn't grow larger, the neurons in the neocortex changed to look like human brain cells, growing thick spines to exchange information with other cells. The neurons also formed 50 to 60 per cent more of these spines than normal mouse neurons do, which would likely increase the brain's processing power.

...The timing of the second duplication 2.5 million years ago, the researchers point out, coincides with when our genus, Homo, began separating from the now-extinct Australopithecus.

We know that the cognitive abilities of Homo must have increased tremendously to enable our ancestors to develop complex social structures and tools that australopithecines didn't have. The rare double gene duplication may have been instrumental in this.

What's interesting about the duplication, Eichler says, is that it would have changed brain development immediately and dramatically. Human ancestors with two, three, or even more copies of SRGAP2 – and consequently stark differences in their cognitive abilities – could have been running around together at one point. "That's fun to think about," he says. _NewScientist

It required a medley of genetic changes to create a viable human brain, capable of growing wildly yet still passing through the female reproductive path intact, capable of taking care of helpless infants for years before they could fend for themselves, capable of learning enough about life in an ever-changing environment to survive the many natural catastrophic changes that inevitably occurred . . . .

Now, scientists are testing some of these developmental theories out on mice and other lab animals -- attempting to grow super-smart animals as proof of concept. But are humans willing to share the planet with other intelligent species? Probably not. At least, not without a few more changes . . . . More on the research findings:

Polleux suspects that the copies might be able to tell us more about conditions like autism, where the connections between neurons (synapses) don’t work normally. Scientists have identified several genetic variants that are more common in autistic people, and they’ve tried to understand the role of these genes by mutating them in mice. But Polleux says that this approach “assumes that synaptic development is the same in mice and humans.” This is probably not true. After all, his team has already shown that adding SRGAP2C to mice changes the nature of their synapses.

The bottom line is that we might never really appreciate the effect of autism genes (or those for other mental disorders) by studying mouse synapses. The background’s all wrong. “If we want to fully understand the function of genes causing autism in humans, we have to understand what is specific about synaptic development in humans,” says Polleux. “Studying human-specific gene duplication might be a very important step in that direction.”

There is still a lot to learn, and remember that SRGAP2 is just one of more than 30 genes that have been duplicated specifically in humans. Several of the others are also involved in brain development and are missing from the human reference genome. The teams are now busy trying to analyse these genes and understand their evolution. “It’s going to take a while to figure this out, but it’s very exciting!” says Polleux.

In the meantime, we are left with a delightful irony: the reference genome, supposedly the full catalogue of human DNA, may be missing some of the elements that most make us human. _Discover

The punchline above should be enough to suggest to persons who are most resistant to the ideas of HBD, that there is a lot more to the story of the divergent evolution of human intelligence than we have heard so far.

“If you’re increasing the total number of connections, you’re probably increasing the ability of this network to handle information,” Polleux says. "It’s like increasing the number of processors in a computer."

In mice, the gene also increased the migration speed of neurons across the developing brain. Polleux's team speculates that this trait could also have helped neurons to travel long distances in the enlarged brains of human ancestors.

“One has to be cautious about putting too much emphasis on the role of one gene in brain evolution,” says Genevieve Konopka, a neuroscientist at the University of Texas Southwestern Medical Center in Dallas....James Sikela, an evolutionary geneticist at the University of Colorado, Denver, adds that the SRGAP2 duplications are likely to be one of a multitude of genetic changes that moulded the human brain. His team has identified dozens of duplicated genes unique to humans3, many of them expressed in the brain. “Finding the genes that make us human may be challenging,” he says, “but the resources we now have to ask such questions are unprecedented.” _Nature

Again, it should be clear that we have just begun to understand how our genetic and epigenetic heritages make us the humans that we are. If we are to hold on to our gains -- and make further advances -- we have to move ahead with open minds and the courage of our ancestors who were able to adapt to virtually all environs of our always changing planet.

Genetic scientist Professor Evan Eichler, of the University of Washington, said: ‘These events could have allowed for radical changes in brain development and brain function.’

In addition to providing insight into the origins of the modern human brain, the findings offer clues to the neurological brain disorders including autism, epilepsy and schizophrenia in which development of cell connections is affected.

The researchers point to known cases of humans with structural brain defects and other symptoms that can be traced to disruption of the ancestral SRGAP2.

They now intend to search for people carrying defects in the human-specific 'granddaughter' copy as well. _DailyMail

Citations for articles published in Cell: