Modern humans carry a surprising legacy from our ancient cousins, the extinct Neanderthals. A new study suggests that archaic genes that most people carry as a result of interbreeding events tens of thousands of years ago may influence our susceptibility to autism.

Researchers found that people with autism have an overrepresentation of specific Neanderthal-derived variations in their DNA compared to control groups. While these variations don’t guarantee autism, they may act as a hidden risk factor, adding another layer of complexity to understanding this neurological disorder.

“This is the first evidence that I am aware of actually showing that Neanderthal DNA is associated with autism,” said first author Alex Feltus, a professor at the Clemson Department of Genetics and Biochemistry. 

A Small but Significant Legacy

Neanderthals, a distinct species from modern humans, interbred with early Homo sapiens after they left Africa but before spreading across Europe and Asia. This interbreeding resulted in a small percentage of Neanderthal DNA — between 1.5% and 4% — in non-African populations today. More recently, researchers found that Homo sapiens also interbred with another extinct relative, the Denisovans. Some of the inherited Denisovan genes protect us from viral infections but may also increase the risk of mental illnesses.

Although the Neanderthal genetic legacy is small, it has significant implications for our physical and mental health. Previous research has connected this genetic legacy to various conditions, including neurological, psychiatric, and immune system disorders. On the flip side, inherited Neanderthal gene variants also boost the immune system and modify sensitivity to ultraviolet radiation.

Now, findings made by researchers from Clemson University and Loyola University suggest you can add autism to this growing list of heritable traits.

The researchers utilized data from public databases to compare genetic traits in autistic individuals, their unaffected siblings, and ethnically matched controls. They focused on single nucleotide polymorphisms (SNPs), the most common type of genetic variation among people. SNPs represent differences in a single DNA building block and can influence gene function, potentially affecting disease susceptibility.

Ancient DNA’s Role in Modern Autism

The analysis identified 25 SNPs linked to brain development that were significantly overrepresented in people with autism. However, these Neanderthal-derived variations do not directly cause autism but rather contribute to a higher susceptibility to the condition. Autism spectrum disorder is likely caused by an umbrella of different genetic factors that we’re only beginning to untangle. Another 2022 study by Mount Sinai researchers identified more than 250 genes with strong links to autism.

“The hypothesis is not, ‘Did Neanderthals give us autism?’ It’s that Neanderthals gave us some of the gene tweaks that give a higher susceptibility for autism,” he said.

This study underscores the intricate nature of genetic inheritance and its impact on modern health. The researchers hope their findings will inspire further investigation into how ancient genes continue to shape brain development, intelligence, and overall human health, particularly concerning autism.

“Autism is a complex trait. It is controlled by many, many genes. A big part of what we do in my lab is try to understand the level of complexity. Of the 60,000 genes in the human genome, how many genes are at play when you’re developing autism or cancer or any other complex trait? We embrace complexity. We don’t try to erase complexity.”

The findings appeared in the journal Nature: Molecular Psychiatry.