DNA changes supercharged the human brain - but at a cost

Scientists have long suspected that unusually rapid changes in our DNA might hold the key to brain evolution.

Researchers have now found that certain stretches of our chromosomes changed more rapidly over time than seen during typical evolution, which may have influenced how our brain’s nerve cells form complex connections.

The research was led by Professor Yin Shen from the UCSF Weill Institute for Neurosciences and the UCSF Institute for Human Genetics. Her team performed experiments on artificial brain cells from humans and chimpanzees to see which genetic features set us apart.

Fast-evolving DNA and brain development

Fast-changing chromosomal regions, known as human accelerated regions (HARs), differ significantly between people and chimpanzees. Experts believe these areas might have helped shape the advanced thinking and language skills that define our species.

Some of these regions appear to influence how neurons send and receive signals. Shen’s group used cutting-edge genetic approaches to find out why these DNA stretches, HARs, had such a strong effect on neuron function.

The team noted that small edits within these regions might have caused a big jump in brain complexity, which could explain the advent of human creativity and problem-solving. It also raises questions about whether these gains come with possible trade-offs in mental health.

Neurite connections and complexity

The researchers noticed that human nerve cells grow multiple neurites, which are tiny branches that help with communication between cells. Chimpanzee neurons in the same setting grew fewer branches, which suggests a more streamlined network.

“More neurites during development could mean more complexity in our neural networks. These networks facilitate the transmission of signals in the nervous system and support our higher cognitive functions,” explained Shen.

The investigations revealed that tweaking chimp cells to include human HARs triggered more branching. The differences hint that our ancestors’ DNA picked up precise mutations that amped up the neuronal wiring of the brain.

Benefits and risks of rapid brain evolution

Researchers point out that advanced wiring may come at a cost. Some HARs appear to link with genes that show up in certain mental conditions, suggesting that our unique cognitive edge might also come paired with vulnerability to certain mental illnesses.

Genes like NPAS3 have been tied to brain development and mental health conditions. Subtle changes in HARs near NPAS3 could shift how much of the gene gets turned on or off in early stages of neuron growth.

The group also examined regions that influence SOCS2, which is connected to neurite outgrowth. Variations in these areas might change how nerve cells shape themselves, possibly swinging the balance between boosting intelligence and elevating the odds of neurological disorders.

Beyond the 1% difference

Studies have estimated that humans and chimpanzees share about 98-99% of their DNA. That small gap includes HARs, which set the stage for distinctive thought processes, social behavior, and more advanced language skills.

This shift in our genomic blueprint is believed to have unfolded relatively fast in evolutionary time. Slight tweaks in just a few spots can have outsized impacts on neuron structure and brain wiring.

Shen’s experiments used modern genetic engineering to introduce human HARs into chimp cells. Watching those lab-grown neurons form new branches helped confirm how these DNA elements shape connectivity.

Future research on DNA and brain function

The scientists are excited about exploring whether changes in these regions hold clues to unexplored cognitive abilities. They want to see whether specific HAR variants spread more quickly than others among early humans.

The researchers are also investigating whether certain DNA shifts might drive differences in brain development across various populations. This could reveal why some communities have increased or decreased risks of suffering brain-related conditions.

Further work will likely look at how HAR-based alterations influence gene interactions in living brains. That might help scientists pinpoint when these genetic quirks first appeared and how they spread in human ancestors.

Broader implications of the research

This laboratory approach offers a peek at how subtle DNA changes can rewrite the instructions for assembling our brains. By comparing the DNA in human and chimpanzee cells, scientists can help map our evolutionary path.

The researchers hope that these findings may guide therapies for disorders linked to abnormal neuron connections. Understanding which DNA sites boost or hamper neurite growth might open opportunities to target them in conditions like autism and related syndromes.

The real excitement lies in how these studies bridge the gap between basic biology and the possibility of medical advances. If scientists can pinpoint how these fast-evolving regions shape neurons, they might uncover ways to preserve healthy brain networks.

DNA research may shape brain health

Researchers envision a time when analyzing HARs becomes routine in identifying early risk markers for certain developmental issues. A single genetic misstep in these areas might cause a ripple effect on how brain cells wire to each other.

The next steps may include testing potential treatments that regulate the expression of crucial genes tied to neuron branching. That might reduce the impact of disruptions that hamper normal growth or communication in the brain.

The research also encourages us to consider our species’ rapid rise in intelligence. Speedy edits in a small stretch of code may have set us on a path to become the tool-making, idea-sharing beings we are today.

The study, which was funded by the National Institutes of Health, is published in the journal Nature.

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