Why is the human brain three times larger than the chimpanzee's brain?

Amazing stuff! A long time ago, a viral infection made our brain grow!

"We humans share nearly 99% of our DNA with chimpanzees—yet our brains are three times larger. To figure out where our brains diverged from those of our closest living kin, researchers looked for clues in our genes.

They found that, sometime between 5 and 7 million years ago, an African ape got a viral infection. Occasionally, as in this ape’s case, a virus inserts some of its own DNA into its host’s genome to tell it to produce more virus. That DNA can stick around long after the infection, get replicated across the genome, and be passed down to future generations—and that’s exactly what appears to have happened. The researchers found that, while the ancient viral DNA showed up in 158 locations across the chimpanzee genome, it’s absent in the human genome .

So, the researchers removed the viral DNA from chimp stem cells using the gene editing platform CRISPR. The removals caused a gene called LINC00662 to turn on; it is normally activated in humans but not chimpanzees. The activation amped up the activity of genes involved in neuron development. Similarly, when the researchers turned off LINC0062 in human cells, the neuron development genes got no boost. ..."

From the abstract:

"Over the past 5 to 7 million years, humans and chimpanzees have diverged in brain size, structure, and cognition despite high conservation of protein-coding genes.

However, retroviral infections within host genomes have introduced numerous species-specific regulatory elements. Chimpanzees harbor lineage-specific PTERV1 endogenous retroviruses that are absent in humans, but their role in brain evolution has remained unclear.

We performed an epigenomic analysis of PTERV1 insertions in chimpanzee neural organoids and found they are heavily DNA methylated, forming over 150 species-specific heterochromatin domains with the potential to influence gene regulation.

We identified a chimpanzee-specific insertion on chromosome 19 that silences the long noncoding RNA LINC00662 through DNA methylation spreading. CRISPR-mediated deletion of this PTERV1 restored LINC00662 expression in chimpanzee induced pluripotent stem cells.

We show that LINC00662, a human-specific transcript expressed during brain development, plays a role in neuronal maturation, axon outgrowth, and neural organoid development.

These findings reveal a mechanism by which endogenous retroviral insertions contributed to human-chimpanzee brain divergence."

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Retroviral insertions contributed to the divergence of human and chimpanzee  brains (open access)

An ancient virus in chimpanzee DNA switches off a gene that is active in humans (original news release) "Humans and chimpanzees share almost all their genes. Despite this, our brains have developed in different ways. Researchers at Lund University in Sweden have now shown that a viral pandemic dating back several million years is likely to be part of the explanation."

Retroviral insertions contributed to the divergence of human and chimpanzee brains (open access)

Fig. 1. PTERV1 insertions form chimpanzee-specific methylated heterochromatin domains in neural organoids.

Fig. 3. LINC00662 is a cytoplasmic human lncRNA expressed during brain development and associated with neurite-related proteins.

Fig. 4. Loss of LINC00662 impairs neurite-associated maturation in human neural organoids.