Researchers have discovered that an ancient viral remnant in the chimpanzee genome silences the LINC00662 gene.
Photo Credit: Fabiana Rizzi
Scientific Frontline: Extended "At a Glance" Summary: Viral Silencing of LINC00662 in Chimpanzees
The Core Concept: An ancient endogenous retrovirus (PTERV1) integrated into the chimpanzee genome millions of years ago, epigenetically silencing the LINC00662 gene through DNA methylation, whereas this same gene remains highly active during early human brain development.
Key Distinction/Mechanism: While humans and chimpanzees share nearly identical genetic repertoires, their gene regulation differs significantly. In chimpanzees, the PTERV1 viral insertion dictates the methylation and deactivation of LINC00662. Removing this viral sequence via CRISPR-Cas9 in chimpanzee brain organoids restores the gene's expression, whereas deliberately silencing it in human organoids impairs nerve cell development and synaptic connectivity.
Origin/History: The PTERV1 endogenous retrovirus infected chimpanzee populations millions of years ago, becoming permanently embedded within their germline DNA and passing to subsequent generations—an infection the human lineage avoided.
Major Frameworks/Components:
- Endogenous retroviruses (PTERV1) and germline genetic integration.
- Epigenetic regulation through systemic DNA methylation.
- Three-dimensional brain organoids derived from induced pluripotent stem cells to model neurological development.
- CRISPR-Cas9 gene editing for targeted sequence excision and gene silencing.
- The LINC00662 gene and its role in neurogenesis and neural circuitry formation.
Branch of Science: Molecular Neurogenetics, Evolutionary Biology, Epigenetics, Virology.
Future Application: Understanding these ancient viral regulatory mechanisms could elucidate the genetic basis of human-specific neurological development and provide novel genomic targets for investigating human brain diseases linked to noncoding DNA sequences.
Why It Matters: This research demonstrates that the cognitive divergence between humans and closely related primates is driven not merely by the presence or absence of specific genes, but by how external environmental factors—such as prehistoric viral pandemics—can fundamentally alter gene expression and evolutionary trajectories.
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.
Pandemics can arise wherever animal or human populations are sufficiently large, and they are not confined to the modern age. Johan Jakobsson, professor of molecular neurogenetics at Lund University, believes that the findings from the new study are highly relevant; they demonstrate that a virus can alter a DNA sequence across an entire population.
“The virus we investigated specifically affected chimpanzees. Yet humans and chimpanzees have largely the same genetic makeup. That is why it is important to understand the differences in how genes are regulated. Our findings suggest that one gene, LINC00662, plays a significant role in early human brain development,” Jakobsson says.
This, Jakobsson adds, advances our understanding of how gene regulation can protect or damage the brain. In the new study, published in Science Advances, the researchers discovered that an ancient viral remnant in the chimpanzee genome silences the LINC00662 gene. This same gene is active in humans and plays an important role in our early brain development. The viral remnant belongs to an endogenous retrovirus, PTERV1—a virus that infected the chimpanzee population millions of years ago. The PTERV1 virus’s genetic material remained in the genome and has since passed down through the generations.
The researchers observed that PTERV1 replicated itself in numerous locations within the chimpanzee DNA, and that these viral sequences are systematically silenced through a process known as methylation—a mechanism that determines which genes are active or inactive.
To investigate how the viral remnant affects brain development, the researchers used human and chimpanzee stem cells to create brain organoids. These three-dimensional miniature organs resemble real brain tissue and display certain characteristics of early brain development. A comparison of the organoids showed that the LINC00662 gene was active in the human models but completely silenced in the chimpanzee models.
“The gene was strongly expressed in the human organoids, but not at all in the chimpanzee organoids,” says Patricia Gerdes, a postdoctoral researcher in molecular neurogenetics at Lund University.
To test whether the viral remnant was responsible, the researchers used the CRISPR-Cas9 gene-editing tool to remove the viral DNA sequence from the chimpanzee cells. Once the viral remnant was removed, the gene was expressed again.
“This shows that it is in fact the viral insertion that is responsible for the gene being switched off in chimpanzees,” Gerdes says.
The researchers also investigated the gene’s apparent function in humans. When they used CRISPR to silence LINC00662 in human brain organoids, this reduced the activity of genes involved in nerve cell development and in the formation of connections between nerve cells.
The findings reinforce the view that humans and our closest relatives differ not only in which genes are present, but also in which genes are active. The researchers will next investigate whether other viral remnants had similar effects during the evolution of the brain, and whether this type of DNA sequence is also linked to brain diseases.
Funding: Swedish Research Council; Swedish Brain Foundation; Cancerfonden; Barncancerfonden; Swedish Government Initiative for Strategic Research Areas (MultiPark & StemTherapy); European Union’s Horizon Europe research and innovation programme
Published in journal: Science Advances
Title: Retroviral insertions contributed to the divergence of human and chimpanzee brains
Authors: Patricia Gerdes, Ofelia Karlsson, Raquel Garza, Diahann A. M. Atacho, Pinghsun Hsieh, Bharat Prajapati, Dongahn Yoo, Chandramouli Muralidharan, Anita Adami, Carrie Davis-Hansson, Emily M. Johansson, Yogita Sharma, Laura Castilla-Vallmanya, Wiktor West, Meghna Vinod, Lucian Domitrovic, Pia A. Johansson, Jenny Johansson, Christopher H. Douse, Chandrasekhar Kanduri, Patric Jern, Evan E. Eichler, and Johan Jakobsson
Source/Credit: Lund University | Erika Svantesson
Edited by: Scientific Frontline
Reference Number: gen102326_01
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