The oldest of all human stories commences with a mistake. It also starts in Africa, of course. Here, in the birthplace of humanity, we see a tribe of Australopithecus species moving across the savannah – hunched down, they are flashing by through the tall grass, covered in sparse, patchy hair, with long jaws, wide cheekbones and strong hands which they use to grab branches, clear the undergrowth and pick fruits. Larger than chimpanzees, although shorter, shorter than 140 cm, these noisy animals are currently running toward night shelter away from predators, males are leading the tribe and somewhat smaller females are carrying younglings around their chest.
The last among them, who had fallen behind, scorned by the others, a female is squeezing her three-month-old baby. Its head is getting bigger day by day, its nose is getting thinner, its cheeks are getting smaller and the crying is getting stronger. As if in an attempt to stop the growth of such a large head, the female is squeezing it ever tighter – hoping that it is not her offspring, as others in the tribe believe, another one of those disfigured weaklings which are occasionally born in the tribe. Until that time, the large-eyed baby tenderly watches the animal carrying it, the wide African sky and the vast savannah, the entire world which is soon to be ruled by it and its race of soft offspring – a completely new species of primates.
It is two and a half million years later. In Montreal, Canada, in a local basilica, the 12th International Congress of the most renowned geneticists starts with a concert. While fickle October is getting on, scholars are getting together at the Palais des congrès de Montréal, a big square building with colourful window panels. While a reception with a dancing performance inspired by DNA code protein formation is underway, and Congress participants are walking around with glasses of champagne, some less notable programmes have already begun.
Thirty-year-old researcher Megan Dennis, a post-doc Asian student at the University of Washington in Seattle, is holding a lecture on the duplicated gene termed SRGAP2C, in room 517D, on the fifth floor of the convention centre. While she is reporting on a discovery of a protein which develops from this duplicated gene and its significance for human brain work, some geneticists become rather excited, but things remain as they are. The news on this discovery presented in Montreal was to be published in October 2011, by the specialized journal Science News, but in the abundance of other science news, its far-reaching consequences would become clearer half a year later.
On the other side of the world, anthropologist Lee Berger is racing in his big jeep, leaving behind a dusty cloud, through a stone landscape of the John Nash Nature Reserve. Together with his regular associate Meshack Kgasi, this famous anthropologist has, for two decades, explored the area of 9,000 hectares northeast of Johannesburg. In this area, along with other numerous regions of eastern and southern Africa, it is possible to find various Australopithecus species fossils, numerous primate species, which evolved from regular monkeys, around four million years ago.
The most famous one definitely belonged to the Australopithecus afarensis species – this is Lucy, a young female who lived around 3.2 million years ago, whose fossils were unearthed in 1974, in the Hadar region in Ethiopia, not far from the so-called ‘cradle of humankind,’ Oldupai Gorge in Tanzania and the Laetoli site, where, in fossilized lava, renowned archaeologist Mary Leaky found 3.6 million-year-old footprints of an Australopithecus female specimen and her small offspring who walked upright.
Judging from the differences in fossil evidence, around 2.5 million years ago, Australopithecus genus evolved into intelligent, human-like primates of the Homo species – with genera almost resembling humans, such as erectus, habilis, Neanderthals and finally sapiens – however, the evolution has always represented the unknown. This Darwin’s ‘missing link’ is one of the more puzzling issues of science. Which species is the transitional one from animals to humans, and Australopithecus definitely were animals although they walked upright? Anthropologist Lee Berger, from the John Nash Nature Reserve, is one of those who believe they have solved this riddle. Here at the Malapa site, he discovered fossils of a new species, the so-called Australopithecus sediba, two million years old, and his paper in the Nature journal attracted a lot of attention at the time, and spawned numerous other mostly genetic studies. Berger is by no means the only anthropologist who has tried to provide an answer to Darwin’s puzzle on the missing link in recent decades – there is a series of transitional varieties, be they specimens of the known or seldom new species, that are being excavated across Africa and other continents, and are inevitably followed by media headlines.
However, despite the number of discovered skeletons and how detailed the reconstruction of fossil remains was, it is difficult to answer how this incredible transformation of a tiny, scared Australopithecus species into an adroit and ingenious Homo species occurred, or to be literal, how did these apelike animals suddenly transform into humans? The final answer, after all, lies in genes.
The Scripps Institute in La Jolla, California, was the first to reveal their secret in 2012. Here were detailed analyses of the two existing copies of the SRGAP2 gene carried out, the very gene whose interesting properties were presented by postdoc student Megan Dennis in Montreal. The research was headed by Professor Evan E. Eichler of the University of Washington, Seattle, who, together with Franck Polleux, discovered when the second copy marked with SRGAP2C developed in the human genome. It turned out that this occurred around 2.5 million years ago – at the time when Australopithecus species evolved into humans.
All these things would not be so impressive if the SRGAP2 gene were not one of those few, i.e. 23, whose copies exclusively exist in humans and not in other primates. Additionally, it is not just any gene. As part of the human genome, it is activated in nerve cells, where it is in charge of the production of the so-called SLIT-ROBO Rho GTPase activating protein 2. This protein has a rather complicated name, but its use is quite simple – migration, that is, the transition of a nerve cell from the place of its birth to the final position in the brain.
Everything is more or less the same as in other similar animal species, apart from one tiny thing. It turns out that the original of the SRGAP2A gene and its two copies (SRGAP2B and SRGAP2C), which are only detected in the primates of the Homo species, do not have the same length. This means that during the duplication of these copies, an error occurred in the genome and that the father, the son and the great-grandson of the gene do not perform the same functions in the same manner. As Evan Eichler himself explained in a scientific paper published in the prestigious Cell journal, errors which copies of this gene have are the ones which actually lead to the developmental slowdown of the brain. This provides more time for the synapses to develop and for the neural network to become significantly ‘more intelligent.’
The puzzle encompassing the African savannah and genetic laboratories is coming together. All in all, around 2.5 million years ago, the copy of the SRGAP2B gene, which existed in Australopithecus species, such as Lucy or Berger’s fossil from South Africa, was duplicated for the second time. An error occurred during this duplication, which brought about a major change in protein production, which is important for neuron migration and brain development. The ones who inherited this ‘erroneous’ copy were inevitably made more intelligent. It made them the first ‘humans.’
Into the legend of Adam’s expulsion from Eden from Moses’ ‘Genesis’, we could now introduce a new comparison of the tree of knowledge with the DNA coil whose gene got out of control. The attractiveness of these kinds of considerations and new arguments in the discussion between evolutionists and creationists notwithstanding, the most exciting part of the story on the gene, which the Homo species created, is practical, laboratory proof of these theses.
Researchers spearheaded by Professor Eichler have implanted a copy of the SRGAP2C gene, which appeared during ‘humanity awakening,’ into the genome of a common mouse, which contains only the original SRGAP2 gene. Something extraordinary happened. With the change in protein production, mice’s brains began to change dramatically, and their synapses started lengthening. With this ‘press on the switch,’ their tiny, animal brains began to turn into something resembling a human brain.
You may find this terrifying, but the SRGAP2 gene change was one of those errors with far-reaching consequences. After 4.5 billion years of gradual evolution, something occurred in the brains of harmless African primates who were roaming the savannah, something that was able to conquer the planet, travel into Space, and write billion of notes and trillions of words. Plus to excavate the good, old, fossilized Australopithecus species. Terrifying or not, the entire planet felt dramatic changes over the following two million years, due to a mistake in gene duplication.
To spice things up, when SRGAP2B transformed into SRGAP2C, which in a mouse’s brain creates a neural network such as the one Michelangelo, Bach and Einstein were born with, it was not the first duplication of the SRGAP2 gene. A million years earlier, around 3.6 million years ago, SRGAP2A turned into SRGAP2B. Coincidentally, this was the time when Lucy and other members of the Australopithecus lineage stopped walking on four feet, and became the first erected beings on the planet. The first mistake in copying this gene, quite possibly, led to them becoming upright, and the second one, as research has us believe, made them into humans. What will the third mistake do? Australopithecus members, running through the savannah, did not anticipate the answer.
S.B.
Photo: Australopithecus sediba – Brett Eloff, Univerzitet Wits – Wikimedia Commons CC4