Recreating Neanderthal Brain Structures with Stem Cells
Written by Kacey Zimmerman
Edited by Sameeha Salman
July 31st 2021
Edited by Sameeha Salman
July 31st 2021
Out of all human-like species that once walked this earth, Neanderthals had the closest relation to modern humans. They lived across Europe and most of Asia approximately 500,000 to 40,000 years ago and spent most of this time in close proximity to our ancient ancestors. This is why many theorize that competition with humans and inbreeding both likely contributed to Neanderthal extinction. In fact, many people carry around 2% Neanderthal DNA in their genome (Hendry, n.d.).
Despite similarities between the two species, one clear morphological difference lies with the Neanderthal skull. Neanderthals possess the easily recognizable brow ridge and a longer, lower skull than humans (Hendry n.d.). Despite common perception, Neanderthals weren’t nearly as primitive as we had once believed, making them a very interesting topic of research (Hendry, n.d.).
Recently, scientists have used human stem cells to study Neanderthal genes (Dannemann et al., 2020). Researchers collected the genomes of 173 people and analyzed them for Neanderthal DNA content. They used this information to assemble a genomic database which was able to account for around 20% of the Neanderthal genome. However, researchers did note that their sample was mostly European, and future studies with Asian populations could bring the percentage up to 40% due to genetic variation within a larger population. Using this information, scientists differentiated stem cells into organoids, collections of brain-like cells, and tracked the RNA transcribed from known Neanderthal genes. This study paved the way for later research on specific effects of Neanderthal DNA on development (Dannemann et al., 2020).
Another team of scientists put this to the test. Researchers analyzed 61 protein-coding genes based on variation between human and Neanderthal genomes, and eventually settled on NOVA1 for their study (Trujillo et al., 2021). NOVA1 controls RNA variation during nervous system development and regulates genes involved in the formation of nerve connections. Researchers used CRISPR-Cas9, a genome editing technique, to replace modern NOVA1 with Neanderthal NOVA1 in human stem cells in order to create genetically modified organoids, small 3D formations of brain-like cells. Though the two alleles only differed by one amino acid, this was enough to affect cell morphology, proliferation, and gene expression. Archaic NOVA1 brain organoids were surprisingly more rough than the typically spherical human organoids. Additionally, the Neanderthal NOVA1 organoids showed differences in excitatory neurons which is thought to be the cause of changes to neural network development (Trujillo et al., 2021).
This research is the first step to not only better understanding our Neanderthal relatives, but also looking deeper into the genes that mark us distinctly as humans by comparing them to the variations of the past.
Work Cited
Danneman, M., He, Z., Heide, C., Vernot, B., Sidow, L., Kanton, S., Weigert, A., Treutlein, B., Pääbo, S., Kelso, J., and Gray Camp, J. (2020). Human Stem Cell Resources Are an Inroad to Neandertal DNA Functions. Stem Cell Reports. 15(1), 214-225. 10.1016/j.stemcr.2020.05.018
Hendry, L. (n.d.). Who Were the Neanderthals? London National History Museum. https://www.nhm.ac.uk/discover/who-were-the-neanderthals.html
Trujillo, C., Rice, E., Schaefer, N., Chaim, I., Wheeler, E., Madrigal, A., Buchanan, J., Preissel, S., Negraes, P., Szeto, R., Herai, R., Huseynov, A., Ferraz, M., Borges, F., Kihara, A., Byrne, A., Marin, M., Vollmers, C., Brooks, A… Muotri, A. (2021). Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment. Science. 371(6530). 10.1126/science.aax2537