Retroviral insertions contributed to the divergence of human and chimpanzee brains
7 affiliations
- 1Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.
- 2Department of Genetics, Cell Biology, and Development, Institute for Health Informatics and Bioinformatics and Computational Biology Graduate Program, University of Minnesota, Twin Cities, MN, USA.
- 3Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, SE-40530 Gothenburg, Sweden.
- 4Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
- 5Laboratory of Epigenetics and Chromatin Dynamics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.
- 6Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
- 7Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.
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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BibTeX
@article{gerdes2026retroviral,
title = {{Retroviral insertions contributed to the divergence of human and chimpanzee brains}},
author = {Patricia Gerdes and Ofelia Karlsson and Raquel Garza and Diahann A. M. Atacho and PingHsun Hsieh and Bharat Prajapati and DongAhn Yoo and Chandramouli Muralidharan and Anita Adami and Carrie Davis-Hansson and Emily M. Johansson and Yogita Sharma and Laura Castilla-Vallmanya and Wiktor West and Meghna Vinod and Lucian Domitrovic and Pia A. Johansson and Jenny Johansson and Christopher H. Douse and Chandrasekhar Kanduri and Patric Jern and Evan E. Eichler and Johan Jakobsson},
journal = {Science Advances},
year = {2026},
month = oct,
doi = {10.1126/sciadv.aeg5791},
url = {https://www.science.org/doi/10.1126/sciadv.aeg5791},
note = {CC BY},
}
RIS
TY - JOUR
TI - Retroviral insertions contributed to the divergence of human and chimpanzee brains
AU - Patricia Gerdes
AU - Ofelia Karlsson
AU - Raquel Garza
AU - Diahann A. M. Atacho
AU - PingHsun Hsieh
AU - Bharat Prajapati
AU - DongAhn Yoo
AU - Chandramouli Muralidharan
AU - Anita Adami
AU - Carrie Davis-Hansson
AU - Emily M. Johansson
AU - Yogita Sharma
AU - Laura Castilla-Vallmanya
AU - Wiktor West
AU - Meghna Vinod
AU - Lucian Domitrovic
AU - Pia A. Johansson
AU - Jenny Johansson
AU - Christopher H. Douse
AU - Chandrasekhar Kanduri
AU - Patric Jern
AU - Evan E. Eichler
AU - Johan Jakobsson
PY - 2026
DA - 2026/10/23
JO - Science Advances
DO - 10.1126/sciadv.aeg5791
UR - https://www.science.org/doi/10.1126/sciadv.aeg5791
AB - 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.
SN - 2375-2548
ER -