“Mini-brains” made in the laboratory by researchers from Brazil and the USA contain in the DNA of their neurons a small part of the genetic material that was present in extinct human species such as Neanderthals. The change triggered significant changes in the functioning of nerve cells. This could be a first step to experimentally study the brain differences between people today and their relatives in the past.
The work is coordinated by the Brazilian biologist Alysson Muotri, who works at the University of California in San Diego. It appears in this week’s issue of Science, one of the most important in the world. Scientists from PUC-PR (Pontifical Catholic University Paraná) and UFABC (Federal University ABC) in São Bernardo do Campo (SP) have also signed the study.
“It’s something that resonates deeper with humans because it’s connected to species that are so close to us, and even more so because it has to do with the brain,” says Alexandre Kihara, professor at the Center for Mathematics, Computer science and cognition from UFABC and co-author of the study. “If it were a Neanderthal’s heart there would of course be some differences from us, but it’s an organ that only pumps blood. The brain stands behind what we think and feel. “
The “mini-brains” are called cortical organoids, very simplified simulations of the dynamics of the cerebral cortex with a diameter of only a few millimeters. To create them, the researchers primarily manipulated genetically engineered pluripotent stem cells, that is, which can lead to any tissue in the body.
Such cells received the archaic version of a gene called NOVA1. This section of human DNA contains the recipe for making a protein that regulates the way cells “read” other genes. The same region of DNA can be read in very different ways, which has important effects on the body. The NOVA1 gene plays this role in key genes for the development of neurons and the connections between them – which of course affects the brain.
Since scientists already have very reliable data on the DNA of Neanderthals and another extinct human species from the Ice Age, the Denisovans (native to Siberia), they know that NOVA1 is one of the genes that is different from modern humans and archaic species functionally always differentiate. All persons examined today carry a mutation in NOVA1 that distinguishes them from their ancestral version (see infographic).
Hence the idea of inserting the archaic form of the gene into human stem cells. These cells were cultured in the laboratory to convert into neurons and form cortical organoids. At the same time, “mini-brains” were created with the version of the gene found in modern humans so that the evolution of the two types of organoids could be compared.
Then various kinds of differences between the small artificial organs became apparent. Initially, those that carried the archaic gene were smaller in diameter and rougher in surface than those made by cells with “pure” DNA from modern humans. Interestingly, however, the real brains of the Neanderthals and Denisovans, as far as we know, were no smaller than ours.
In addition, organoids with archaic DNA carried cells that reproduced less and with higher rates of apoptosis (programmed cell death) of neuronal progenitor cells, that is, those that produce neurons that are considered mature. On the other hand, the electrophysiological activity of the organoids – that is, the messages carried between them by electrical impulses – turned out to be more complex in those who had the archaic version of the gene, rather than those who carried the entirely modern DNA.
One possible explanation for these paradoxical data, according to Kihara, is the fact that, to the best of our knowledge, older human species, as we see them in contemporary primates, developed their nervous systems faster than modern humans. Organoids with the archaic gene would also form complex networks more quickly than those with modern genes. Ultimately, however, this is not exactly an advantage for the Archaics: it is precisely the relatively slow pattern of brain development that gives the behavior of Homo sapiens more flexibility.
It’s just the beginning of the job, of course. One way to investigate is to computer simulate the effects of differences in connections between neurons on cognition. Would the presence of the archaic gene change the way extinct people process information? In the future it will also be possible to study the effects of other genetic differences between species.