A recent study published in Molecular Psychiatry reveals that certain genetic traits inherited from Neanderthals could significantly contribute to the development of autism. This groundbreaking research shows that specific Neanderthal genetic variants may influence susceptibility to autism, suggesting a link between our ancient relatives and modern neurodevelopmental conditions.
The study was motivated by long-standing curiosity about how archaic human DNA, particularly that of Neanderthals, influences modern human health. Homo neanderthalensis, commonly known as Neanderthals, are our closest known cousins on the hominid tree of life. Populations of European and Asian origin are estimated to have about 2% Neanderthal DNA, a remnant of interbreeding that occurred when anatomically modern humans migrated out of Africa about 47,000 to 65,000 years ago.
While previous studies have identified Neanderthal genetic contributions to traits such as immune function, skin pigmentation and metabolism, the role of these ancient genes in brain development and in neurodevelopmental conditions like autism has remained largely unexplored. In their new study, the researchers sought to fill this gap by testing whether Neanderthal DNA is more prevalent in autistic people than in non-autistic controls.
Autism is a neurodevelopmental disorder characterized by difficulties with social interaction, communication, and repetitive behaviors or restricted interests. The severity and specific manifestations of these traits can vary greatly among individuals. Since autism is characterized by distinct patterns of brain connectivity, researchers sought to better understand whether these patterns could be linked to Neanderthal DNA.
“I should point out that I myself am on the autistic spectrum. I have been involved in the online autistic and neurodiversity communities since around 2003. I was a moderator on the well-known forum Wrong Planet, under the handle “Sophist”, and later developed my own website on the “autism called Gestalt,” the study explained. author Emily Casanova, assistant professor of neuroscience at Loyola University New Orleans and creator of the website Science Over a Cuppa.
“I have been interested in autism and finding out what motivates it for a long time. Over the last decade I have focused more on genetics, but have also had an abiding interest in evolutionary biology. For many years the latter interest was just a hobby, but in recent years I have started working more on things like studying the evolution of autism genes and simply trying to understand how many of these development-related genes change over time.
“You may be wondering what this has to do with Neanderthals! Well, one of the topics I studied is how hybridization (the bringing together of two species) influences the offspring of subsequent generations,” Casanova continued. “Hybridization tends to ‘shake things up’ genetically – not just because you’re putting two species together in an additive process – but because some genetic variants don’t always work as well when suddenly joined together into a single genome. »
“Variants tend to have partners they like to ‘travel’ with over generations and when sexual recombination separates them, it can sometimes create new problems in the offspring. Interestingly, this process can also stimulate faster evolution after hybridization.
“So I’m very interested in these Neanderthal variants, not only to understand how they may influence susceptibility to autism, but also how they might have guided our own subsequent brain evolution over the last 50,000 years,” he said. -she explains. “I don’t think it’s a coincidence that many of the variants involved in autism are also involved in human intelligence, so I find this possibility fascinating.”
The research team used whole exome sequencing (WES) data from the Simons Foundation Powering Autism Research (SPARK) database, focusing on people with autism and their unaffected siblings. They compared these groups to individuals from the Genotype-Tissue Expression (GTEx) and 1000 Genomes (1000G) databases. Specifically, the researchers looked at Neanderthal-derived single-nucleotide polymorphisms (SNPs), which are variations of a single building block of DNA.
Researchers found that autistic individuals had a higher prevalence of rare Neanderthal-derived genetic variants compared to non-autistic controls. These rare variants, which occur in less than 1% of the population, were significantly enriched in the genomes of autistic individuals from three major ethnic groups: non-Hispanic blacks, white Hispanics, and non-Hispanic whites.
“I know a lot of people will read the headline and immediately assume that autistic people have more Neanderthal DNA than non-autistic people — that they are somehow ‘more Neanderthal,’” Casanova told PsyPost. “I wouldn’t say I blame them for this hypothesis, especially when the “Neanderthal theory of autism” had already been proposed and popularized by Leif Ekblad, an independent autistic researcher, as early as 2001. This idea made its way into the whole world. online autism community in the early 2000s and served in part as the inspiration for Ekblad’s “Aspie Quiz”, which continues to be one of the most popular online autism quizzes.
“Our results are a little more nuanced than ‘autistic people are just more Neanderthals.’ As a reminder, the human genome is made up of more than 3 billion pairs of nucleotides. The vast majority of our genomes are quite identical to each other. But there are a few places in the human genome that are sites of variation. »
“Neanderthal DNA provides some of this variation and some of these variants are common (1% or more of the population has this particular variant) or they may be rare (less than 1% have this variant),” explained Casanova. “In our study, we found that people with autism have, on average, more rare Neanderthal variants, not that they have more Neanderthal DNA in general. This means that while not all Neanderthal DNA necessarily influences susceptibility to autism, a subset does.
Unlike rare variants, the study found that common Neanderthal-derived variants were less prevalent in non-Hispanic Black and White Hispanic autistic individuals compared to controls. Common variants are those present in 1% or more of the population. This finding was not observed in non-Hispanic white autistic individuals, who did not show significant differences in common Neanderthal DNA compared to controls or unaffected siblings.
The researchers also identified specific clinical associations between Neanderthal-derived variants and traits linked to autism. For example, a particular SNP (rs112406029) in the SLC37A1 gene was significantly associated with epilepsy in non-Hispanic white autistic individuals. This variant was more common in autistic people with epilepsy than in those without it, and was even more prevalent in people with a family history of the condition.
Similar associations have been found in other ethnic groups, linking certain Neanderthal variants to traits such as intellectual disability, language delay, and language regression. These results suggest that Neanderthal-derived genetic variants may not only contribute to autism susceptibility, but also influence specific comorbid conditions and traits.
“I was quite surprised to find that many of the Neanderthal-derived variants we found that were associated with autism varied significantly by ethnic group,” Casanova said. “In hindsight, I suppose this shouldn’t be that surprising, but it means that many of these weak variants that play a role in autism are influenced by the background genome, which varies by origin ethnic.”
“Thus, one variant may be strongly linked to autism in Black Americans, while that same variant does not appear to play a measurable role in white Hispanics and non-Hispanics. To me, this suggests that our tendency to “whitewash” genetics and ignore variants that are not involved in all genetic backgrounds means that we are missing many important genetic factors.
The findings have significant implications for our understanding of autism and its genetic underpinnings. By highlighting the role of ancient Neanderthal DNA, the research opens new avenues for exploring how hybridization events between archaic and modern humans shaped neurodevelopmental conditions.
“In this current study, we only studied the parts of the genome that contain protein-coding genes (called exome),” Casanova noted. “In the next phase, we plan to look at the whole genome, because these regions contain many interesting regulatory elements that undoubtedly influence when and how genes are expressed. We also plan to include the Denisovan genome in our next phase of study to see if this DNA may play a role in autism in people of Asian/Native American descent.
“Some people within the autistic community feel uncomfortable with genetic studies,” the researcher added. “This is partly explained by fears related to eugenics. The autistic community is well aware of how prenatal genotyping for Down syndrome led to abortion in approximately 30% of cases. But I would just like to assure people that these Neanderthal-derived variants also occur in people, especially family members, who are not autistic. So while identifying these susceptibility factors can help us paint a more complete picture of autism and its very complex roots, this knowledge cannot be used to contribute to eugenics or similar programs. .
The study, “Enrichment of a subset of Neanderthal polymorphisms in autistic probands and siblings,” Rini Pauly, Layla Johnson, F. Alex Feltus, and Emily L. Casanova.