Neanderthal genes can change clusters of human brain tissue, scientists find

Alysson Muotri, a professor at University of California San Diego School of Medicine, and his team created brain organoids genetically modified to carry a gene that belonged to Neanderthals but not Homo sapiens.

(CNN)Brains are not preserved in the fossil record, making it impossible to know how modern human brains differ from our long-extinct ancestors, the Neanderthals.

From fossilized skulls we know that their brains were big -- slightly bigger than ours, in fact -- but they tell us little about their neurology and development.
Scientists from the University of California San Diego have come up with an exciting and provocative way to begin to answer this question. They have created blobs of brain tissue genetically modified to carry a gene that belonged to Neanderthals and other archaic hominins but not Homo sapiens.
    While the research is at a very early stage, the researchers found that the Neanderthalized brain organoids produced significant changes in how the brain is organized and wired.
      "The question here is what makes us human," said Alysson Muotri, professor and director of the Stem Cell Program at the University of California San Diego School of Medicine's Institute for Genomic Medicine.
      "Why are our brains so different from other species including our own extinct relatives?"


        Muotri, who has so far spent eight years on the project, calls his work "neuroarchaeology."
        "When you find a piece of bone or (charcoal) and you try to reconstruct how that society lived, what they were doing, how they connected with each other -- you try to understand the mind. We are doing the same at the genetic level."
        The work combines three cutting-edge areas of science: sequencing ancient DNA, CRISPR gene editing and organoids. Organoids are miniature organs made from stem cells of individuals -- they have allowed medicine to test drugs safely outside the body, personalizing and revolutionizing areas of medical innovation such as cancer treatment.
        Neanderthalized brain organoids (left) look very different than modern human brain organoids (right) -- they have a distinct shape, and differ in the way their cells proliferate and how synapses form.
        The Neanderthalized brain organoids were a "popcorn shape" compared to the more rounded, even shape of the modern human ones, Muotri said. His team also observed that the neurons in the organoids matured faster than the modern human ones.
        "The neurons in the archaic version organoids, we see more activity in the very early stages than the modern human ones. We were definitely not expecting that."
        He said that he had observed similar activity in his previous work on chimpanzee organoids.
        "A baby chimpanzee can outsmart a human newborn by far. We need time to nurture our babies until they become independent. We don't see that in other species. I think what we're seeing here is something similar."
        However, Muotri stressed that this was speculative. Organoids are a long way from real brains. For one, they lack connections to other organs.
        "We don't know how the human brain carrying these archaic versions will behave," he said. "All these differences we see at the early stages could go away because the brain has ways to compensate."