Humans and chimpanzees share more than 96% of their protein-coding DNA, yet the human brain is about three times larger and more complex. A study led by scientists at Lund University suggests that one factor in this divergence may be an ancient retroviral infection that entered the germ line of chimpanzee ancestors millions of years ago but did not reach the ancestors of humans.
“Over the past five to seven million years, humans and chimpanzees have diverged in brain size, structure, and cognitive abilities, despite a high degree of conservation of protein-coding genes,” said the study’s lead author, Professor Johan Jakobsson of Lund University.
“The majority of the primate genome sequence is made up of transposable elements, one major family of which is the endogenous retroviruses, which have expanded throughout primate evolution,” Jakobsson said. “In humans and chimpanzees, at least 8% of the genome is made up of retroviruses.”
An ancient viral insertion
Jakobsson and his colleagues focused on a retrovirus called PTERV1. The virus entered the germ line of African great-ape ancestors approximately 5 to 7 million years ago, leaving copies of its genetic code in the genome.
The chimpanzee genome contains at least 150 PTERV1 insertions, whereas the human genome contains none.
“The virus we studied particularly affected chimpanzees,” Jakobsson said. “But humans and chimpanzees have almost the same genetic makeup, which is why it’s important to understand the differences in how genes are regulated.”
To investigate those regulatory differences, the researchers grew small clusters of developing brain tissue, known as neural organoids, from human and chimpanzee stem cells.
Using long-read DNA sequencing, they found that nearly all of the PTERV1 insertions identified in the chimpanzee genome were heavily tagged with methyl groups. DNA methylation is a chemical marking process commonly associated with gene silencing.
A gene active in human brain organoids
The researchers then searched for genes containing PTERV1 insertions that behaved differently in the two species. One prominent example was LINC00662, a gene that produces a long non-coding RNA.
LINC00662 was highly active in the human organoids but silent in the chimpanzee organoids. In chimpanzees, an approximately 7,000-letter viral insertion lies within the gene, and the surrounding DNA is highly methylated.
The insertion appears to be present in chimpanzees and bonobos, but not in the other great apes examined in the study.
“This gene was strongly expressed in human organoids, but not at all in chimpanzee organoids,” said first author Patricia Gerdes, a postdoctoral researcher at Lund University.
In human cells, LINC00662 was most active during early fetal brain development. When the researchers silenced the gene in human organoids, the tissue showed weaker staining 30 days later for markers of young neurons in regions where newly formed neurons were growing fibers.
Genes involved in the growth of axons and dendrites became more active after the gene was silenced. The researchers interpreted this change as a possible compensatory response.
“Our findings reveal a mechanism by which endogenous retroviral insertions contribute to human and chimpanzee brain divergence,” the scientists concluded.
The study was published on October 23 in Science Advances.
Study: Patricia Gerdes et al., 2026, “Retroviral insertions contributed to the divergence of human and chimpanzee brains,” Science Advances 12(43), doi: 10.1126/sciadv.aeg5791.
Source: www.sci.news