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Human evolutionary information can be accessed from ancient fossils and bones. Fossils record suggested that Neanderthals interbred with the ancestors of modern humans. Neanderthals appeared at least 200,000 years ago and were comprehended by early modern Humans (Homo sapiens) between 35,000 years ago. The reason behind Neanderthal disappearance raised questions in the mind of people, and this issue has been addressed in the early 21st century with the help of genetic tools and techniques. Comparison of modern human DNA and ancient DNA, recovered from Neanderthal fossils, suggested that the origin of modern humans was a speciation event. Although we share genetic similarity with our Neanderthal cousins, still there are specific DNA regions which show genetic variations. Genetic variation is the variation of DNA sequences that makes all of us unique in terms of hair color, skin, and shape of the face. These genetic variations may also play a key role for traits that make us different from our extinct relatives. Therefore understanding the mechanism behind the genes responsible for genetic variation will help us to know the traits which make us unique.
In this direction Alysson Muotri and his team at the University of California published a research article in Science, Muotri’s team indexed the differences between the genomes of the Neanderthals, Denisovan, and diverse modern human populations. Researchers used stem cells to engineer a “Neanderthal-like” brain. Stem cells are special human cells that are able to develop into many different cell types. Initially, they found that 61 genes are different between modern humans and Neanderthals.
One of them is NOVA1, a master gene that regulates many other genes during early brain development. It also plays a role in regulating the formation of synapses between neurons. CRISPR, a powerful gene-editing tool was used to change the single base pair mutation (change in DNA sequences) in NOVA1. This genetic tool efficiently converted modern human genes into a Neanderthal version. In the lab, researchers cultivated stem cells that eventually converted into Neanderthal-like brain organoids (3D brain). Lab-grown brain organoids are useful models for disease development study, genetics, infections, and therapeutic study.
Muotri’s team has visually observed the difference between the size of a lab-grown brain and the modern human brain. Lab-grown brains were smaller in size with convoluted surfaces. NOVA1 induces a significant change in 227 genes’ activity and expression, including those which are involved in brain development. His team found that lab-grown brains work differently than modern human brains in terms of cell proliferation, synapse formation, and neuron interaction. At the molecular level researchers observed that proteins involved in synapse also differ. The Neanderthal neurons also have fewer synaptic connections, which represents an abnormal neuronal network while the modern human brain has sophisticated neural networking.
Single magic gene mutation induces a dramatic change in brain function in modern humans. Muotri’s team said that next, they want to explore the other remaining 60 genes in detail, to see what happens when each or combination of more than two is changed.
