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Can one gene alteration separate modern humans and our predecessors?

How many differences are there between Homo Sapiens and our early human counterparts? Homo Sapiens continue to thrive on Earth whilst Neanderthals and Denisovans became extinct around 40,000 years ago. The reason why Neanderthals and Denisovans faced extinction remains a controversial and divided topic. However, new research published in the journal Science has offered exciting new insight into the way Homo Sapiens’ brains have evolved in comparison to other early humans. 

Neanderthals lived between around 130,000 to 40,000 years ago and share about 99.7% of their DNA with modern humans. Homo Sapiens lived alongside Neanderthals and Denisovans for some time. Even today, modern humans may have some genetic material which can be traced back to these early humans. The use of fossil analysis has been a common way scientists have been able to sequence the genome of Neanderthals. Comparing early human genomes to that of Homo Sapiens has offered scientists an insight to see where modern humans differ from their earlier counterparts. A new technique, developed by Professor Alysson Muotri, a senior author of the study, has offered further insight to a part of the body which so far has evaded scrutiny – the brain. As brains do not fossilise, previous fossil analysis techniques have not been able to examine how Neanderthal or Denisovan brains developed in comparison to human brains.

What is surprising about this research is the significant difference one gene alteration can make to the organoids

Muotri considered the use of stem cells which can specialise into lots of other different cells. The study used CRISPR gene editing which can find and alter specific pieces of DNA. This technique has helped to create Neanderthal-like brain organoids by altering one gene in human DNA to better represent that found in Neanderthal DNA. These organoids are small, brain-like structures which can be grown on petri dishes. Though there is a lack of connection between these organoids and organ systems, organoids can be useful tools for geneticists. Muotri and his team have been able to ensure organoids can even produce organized electrical oscillatory waves like the waves created by the human brain. This technique has previously been used to compare humans with other primates, but this is the first time the technique has been used to compare humans with an extinct species. Even to the human eye, the organoids produced with human DNA and the altered DNA with a NOVA1 Neanderthal-like mutation look different. The NOVA1 gene is particularly interesting, it influences many other genes during early brain development. Inclusion of the NOVA1 gene altered the way cells multiplied and how neurone synapses formed. Muotri states: “We don’t know exactly how and when in our evolutionary history that change occurred. But it seems to be significant.” The organoids produced showed  neural network changes similar to those of a new born non-human primate.  

NOVA1 was one of 61 genes identified in the study which differed between modern humans and Neanderthals. Evaluating the differences between the human and Neanderthal mind will provide greater evidence to help scientists visualise the mind of other early humans. What is surprising about this research is the significant difference one gene alteration can make to the organoids. Muotri continues; “This study focused on only one gene that differed between modern humans and our extinct relatives. Next we want to take a look at the other 60 genes, and what happens when each, or a combination of two or more, are altered.” This research offers opportunity to investigate the different capabilities of modern humans when compared to our extinct counterparts, with a focus on; “social behaviour, language, adaptation, creativity, and use of technology” says Muotri. Further down the line there are hopes this study can contribute to our understanding of the mind of our ancestors. Professor Katerina Semendeferi, co-author of the study says, “We will merge and integrate this amazing stem cell work with anatomic comparisons from several species and neurological conditions to create downstream hypotheses about brain function of our extinct relatives.”  



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