Neanderthal genes altered neurodevelopment in modern human brain organoids

AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE—Building modern human brain organoids with the Neanderthal variant of a gene has provided a glimpse into the way substitutions in this gene impacted our species’ evolution. The ability to grow brain organoids with specific archaic genes provides a way to identify and evaluate the functional differences between the closely related genomes of hominin lineages and explore the evolutionary changes that underly the unique traits that set us as modern humans apart from our extinct relatives. While the genomes of modern humans and their archaic Neanderthal and Denisovan relatives are, in many respects, similar, the genetic differences between them are of particular interest, as they could inform on important traits for recent human evolution. For example, each contains NOVA1, an evolutionarily conserved gene known to play key roles in neurodevelopment and function. However, there are protein-coding differences between modern and archaic human variants. To evaluate the functional importance of NOVA1 variants, Cleber Trujillo and colleagues isolated the archaic NOVA1 gene from the Neanderthal genome and used CRISPR-Cas9 technology to introduce the variant into human pluripotent stem cells. This allowed Trujillo et al. to generate modern human cortical organoids expressing the archaic variant. According to the results, the addition induced slower development and higher surface complexity in cortical organoids, as well as differences in the brain’s electrophysical properties. The authors suggest that this genetic divergence may have had functional consequences for the evolutionary development of modern humans.

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