The Human Brain Owes Its Existence to a Prehistoric Pandemic

Seven million years ago, the evolution of humans and chimpanzees suddenly split from their common ancestor. New research finds that a retroviral infection inserted viral DNA into the genome of early chimpanzees can account for the enormous increase in size and cognitive power of the human brain.

Remarkably, humans and chimpanzees share 98.8 percent of the same genes, but the differences between chimps and humans are astonishing. The human brain is three times bigger than the chimp brain, our closest evolutionary ancestor. That enormous brain gives humans unparalleled superintelligence for complex thought, language, and technology, from stone tools to supercomputers to spacecraft. But, the transformation of the human brain is not easily accounted for by the few genes that differ between us and chimps. How the human brain suddenly ballooned in size and achieved unsurpassed cognitive power is a long-standing mystery in evolutionary biology.

A new study published this week in the journal Science Advances has uncovered a surprising answer. A retroviral infection seven million years ago split the evolution of the human brain from that of chimpanzees.

The difference between humans and chimps is not so much in their genes, but rather in how human genes are controlled. There are many complex mechanisms regulating when a particular gene is turned on or off, which operate through stretches of DNA between genes, called introns. Chemical modifications of DNA, called epigenetic regulation, also dictate whether or not specific genes are expressed. The new study finds that an ancient viral infection affected how key genes for brain development are controlled.

Viral Hacking Into DNA

Retroviruses, like the HIV virus, do not have the cellular machinery to replicate themselves. Instead, they hijack a cell’s genetic program to force it to make viral proteins. The retroviruses reverse engineer the normal process of DNA making RNA to make proteins, by slipping their viral RNA into cells. This gets converted into DNA, and when the cell reads out its genetic program, it unwittingly makes viral RNA and viral proteins, much like malicious code hacked into a computer program.

Snippets of DNA from retroviruses can get integrated into germline cells and passed on for generations. Typically, these fragments of viral DNA no longer make viral proteins, but they alter how genes are regulated. Eight percent of the human and chimpanzee genome consists of snippets of DNA hacked into their genome by ancient retroviral infections, according to the authors. Sometimes retroviral DNA causes dreadful diseases, but other times, the changes in the way genes are expressed can produce beneficial effects that can cause a sudden evolutionary change or even launch a new species.

Retroviral DNA Regulates Genes that Control Brain Development

The new study, led by Johan Jakobsson of Lund University in Sweden, identified a snippet of retroviral DNA, called PTERV1, inserted into chimpanzee DNA. This retroviral DNA, which is absent in humans, does not make a protein, but it alters how other genes are expressed. PTERV1 is heavily modified by methylation, an epigenetic means of silencing genes. The researchers found that this retroviral DNA silenced a human-specific RNA (LILNC00662) that controls many other genes important for brain development.

The researchers used chimpanzee and human stem cells to create organoids (‘minibrains’) in cell culture. This enabled them to insert PTERV1 into the human organoids and remove it from the chimpanzee organoids. LILNC00662 was completely absent in the chimpanzee minibrains, because the PTERV1 insert blocked its genetic readout by causing an epigenetic change (methylation) that suppresses gene expression.

Human minibrains, which lack PTERV1, expressed LILNC00662 at high levels, and they also expressed many other genes important for neural development that LILNC00662 activates. Using various means to manipulate the expression of LILC00622, the researchers found that when this RNA was silenced in human minibrains, neural development was impaired. When they deleted PTERV1 in chimpanzee minibrains, LILNC00662 was expressed as it is in human brains.

Since PTERV1 is completely absent from humans, the authors theorize that it must have resulted from a retroviral infection in the ancestors of African apes about 5 to 7 million years ago. They surmise that either the human and chimpanzee ancestors did not occupy the same habitat at the time of the viral infection, or the human ancestors were resistant to this infection. Evidence in favor of the latter hypothesis is that humans have a protein (TRIM5alpha) with antiviral activity that could have prevented humans from being infected.

Viral DNA Hidden Between Genes

Those seeking to identify what genes in humans could account for our superior brain would not detect this DNA insert because it does not code for a gene itself. It acts by regulating the readout of many other genes that are shared by chimpanzees and humans to guide brain development.

This is an interesting example of evolution that does not conform to classical Darwinian mechanisms of selecting favorable traits from minor variations over generations. In this case, a sudden major morphological and physiological change in a species occurs, because the engine of evolution, DNA, is suddenly hijacked by a virus.

Pandemics are scourges, but one that afflicted primates millions of years ago separated the evolution of chimpanzees from humans and gave rise to the extraordinary human brain. Ironically, the most advanced brain on earth owes its existence to the most primitive form of life there is.

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