LINC00662 PTERV

Over the past 5–7 million years, humans and chimpanzees have markedly diverged in brain size, structural complexity, and cognitive abilities despite high conservation of protein-coding genes. Notably, the endogenization and proliferation of retroviral infections within host genomes has introduced numerous species-specific regulatory elements that have the potential to influence gene regulation. However, the role of these endogenous retroviruses in hominoid brain evolution remains unclear. The PTERV1 retroviruses recently invaded the chimpanzee genome, but are absent in humans. We identified a chimpanzee-specific PTERV1 insertion on chromosome 19 that blocks the expression of the long non-coding RNA LINC00662, via DNA methylation spread to the adjacent genomic region. The expression of LINC00662 was restored in chimpanzee induced pluripotent stem cells when we deleted the PTERV1 insertion using CRISPR editing. We found that LINC00662 is a human-specific RNA that is highly expressed in the developing brain and plays an important role in neuronal maturation, axon outgrowth, and neural organoid development. In summary, our findings describe a retroviral insertion that contributed to the functional divergence of the human and chimpanzee brains. This provides a new mechanism by which retroviral pandemics influenced primate brain speciation.