What is the main difference between modern humans and our closest relatives, Neanderthals and Denisovans? For Neanderthals, there doesn’t seem to be any kind of obvious difference. They used sophisticated equipment, created art and established themselves in some very harsh environments. But, as far as we can tell, their overall population was never particularly large. When modern humans arrived on the scene in Eurasia, our numbers increased, we spread even further, and Neanderthals and Denisovans were displaced and eventually became extinct.
With our ability to obtain ancient DNA, we have now taken a look at the genomes of both Neanderthals and Denisovans, allowing us to ask a more specific question: Could some of our differences be due to heredity?
The three species are close relatives, so the number of differences in our proteins is relatively small. But a large, international research team has identified one and modernized it and engineered it back into stem cells obtained from modern humans. And the researchers found that the neural tissue made up of these cells differed significantly from the tissue grown with the modern human version of this gene.
Not quite a super nova
As a first step in their work, the researchers had to decide on a gene to target. As we mentioned above, the genomes of all three species are very similar. And the similarity only increases when you look at the parts of the genome that encode the protein. An additional complication is that some versions of the gene found in Neanderthals are still found in a fraction of the modern human population. What the researchers wanted to do was to find a gene where both Neanderthals and Denisovans had one version and almost all modern humans had another.
Out of thousands of genes, they found only 61 who passed the test. Was told what they chose to focus on NOVA1. Despite the explosive name, NOVA1 Originally named after being found to be associated with cancer: Neuro-cncological ventral antigen 1. A glance through the Vertibrate Family Tree shows that Neanderthals and Denisovans share its version. NOVA1 With everything from other primates to chickens, that means it was present in ancestors that mammals share with dinosaurs.
However, almost all humans have a different version of the gene (in search of the quarter-million genomes in the database, researchers were able to identify only three patterns of the Neanderthal version). This difference is subtle – the switching of closely related amino acids to the same location of a gene – but it is a difference. (For those who care, it’s Isolysin from Valoin.)
Also NOVA1 There is a type of gene where small changes can potentially have a big impact. RNA That which is used to make proteins is initially made from a mixture of useful parts separated by useless spacers that need to be extracted. For some genes, different parts may be sprayed together in more than one way, specific forms of the protein being made from the same RNA. NOVA1 It controls the division process and can activate what type of multiple genes are formed in cells where it is active. For NOVA1, Where those cells are active it contains many parts of the nervous system.
If those last paragraphs were somewhat confusing, the short version is: NOVA1 Can alter the types of proteins formed in nerve cells. And, behavior is an area where modern humans may differ from Neanderthals, so it is an interesting goal of this type of study.
On our nerves
Naturally, there are moral problems trying to see what the Neanderthal version will do in real humans. But some of the technologies developed over the last few decades now allow us to approach the question in a very different way. First, the researchers were able to take cells from two different people and transform them into stem cells, capable of evolving into any cell in the body. After that, they used the CRISPR gene-editing technique to convert the human version of the gene to the Neanderthal version. (Or, if you’re less charitable, you can call it the chicken version.)
It indicates that after extensive investigations NOVA1 Was the only gene mutated by acquisition, the researchers induced stem cells to form typical neurons of the cerebral cortex.
Clusters of neural cells that resulted in them being smaller when they were formed by cells of the Neanderthal version NOVA1, Although the surface complex of these clusters is more complex. Cells with the Neanderthal version also grew more slowly and tend to go through a process that more often ends in cell death. It was therefore clear that the Neanderthal version changed the behavior of stem cells as they were transformed into nerve cells.
Differences were also evident at the genetic level. The research team discovered any genes that altered activity in cells with Neanderthals (such as those measured by messenger RNA levels). NOVA1. There were many of them, and some of them are key regulators of neural development. And, as expected by a divisive regulator, there were hundreds of genes that mutated their protein-coding RNA. Seeing the change in how we changed together.
Many of these genes appear to be involved in the formation and activity of synapses, the individual connections between nerve cells that allow them to communicate with each other. Not surprisingly, this changed the behavior of those connections. In general, nerve cells in culture form connections and coordinate their activity. In cells with Neanderthal version NOVA1, There was low coordination and the background of the nerve cells was firing signals at random.
A matter of context
The results clearly show that Neanderthals belong to the version NOVA1 Not a good thing for modern human nerve cells. It will still take a little more work, however, all the changes described here are the product of the distinctive difference between the two forms of protein that result in nerve cells being undesirable due to genetic irregularities.
But researchers also warn against explaining the results in general – while indicative, these results are not a clear indication that gene mutations make our brains fundamentally different from those of our closest relatives.
The evolution of the human version of this gene took place against the background of many other subtle changes in human genes, in their coding sequences or (often) in the sequence that controls their activity. Due to differences in the activity of the modern human version of, those changes can offset any potentially harmful effects. NOVA1. A sudden re-reduction in the original version of a gene can only produce a matching difference between a gene and all of those returns.
Therefore, it will take some time to sort out how much of a difference this one gene has to the human and Neanderthal brain. But the main thing is that now it is all possible to ask these questions. The techniques used to generate these results did not exist before this century – CRISPR gene acquisition is less than a decade old. So, it’s amazing that we just know this so much.
Science, 2021. DOI: 10.1126 / Science.X2537 (About DOI).
