Ancient Neanderthal DNA Found to Influence Autism Susceptibility
Exploring the Influence of Ancient Neanderthal DNA on Modern Neurodevelopmental Conditions
Genetic Legacy: Neanderthal DNA and Autism
A recent study published in Molecular Psychiatry1 reveals that certain genetic traits inherited from Neanderthals may significantly contribute to the development of autism. This groundbreaking research shows that specific Neanderthal genetic variants can influence autism susceptibility, suggesting a link between our ancient relatives and modern neurodevelopmental conditions.
The Curious Case of Neanderthal DNA
The study was motivated by a longstanding curiosity about how archaic human DNA, particularly from Neanderthals, influences modern human health. Homo neanderthalensis, commonly known as Neanderthals, are our closest known cousins on the hominin tree of life. It is estimated that populations of European and Asian descent have about 2% Neanderthal DNA, a remnant from interbreeding events that occurred when anatomically modern humans migrated out of Africa around 47,000 to 65,000 years ago.
While previous studies have identified Neanderthal genetic contributions to traits like immune function, skin pigmentation, and metabolism, the role of these ancient genes in brain development and neurodevelopmental conditions like autism has remained largely unexplored. The researchers aimed to fill that gap by investigating whether Neanderthal DNA is more prevalent in autistic individuals compared to non-autistic controls.
Autism and Neanderthal Variants
Autism is a neurodevelopmental condition characterized by challenges in social interaction, communication, and repetitive behaviors or restricted interests. Given that autism is characterized by distinct patterns in brain connectivity, the researchers sought to better understand whether these patterns could be linked to Neanderthal DNA.
Emily Casanova, an assistant professor of neuroscience at Loyola University New Orleans, explained,
"Hybridization has a tendency to ‘shake things up’ genetically — not just because you’re splicing two species together in an additive process — but because some genetic variants don’t always work so well when they’re suddenly thrown together in a single genome."
Casanova and her team utilized whole exome sequencing (WES) data from the Simons Foundation Powering Autism Research (SPARK) Database, focusing on autistic individuals and their unaffected siblings. They compared these groups against individuals from the Genotype-Tissue Expression (GTEx) and 1000 Genomes (1000G) databases, specifically examining single nucleotide polymorphisms (SNPs) derived from Neanderthals.
Key Findings: Rare Variants and Autism
The 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 across three major ethnic groups: Black non-Hispanic, white Hispanic, and white non-Hispanic.
Casanova emphasized,
"Our results are a little more nuanced than ‘autistic people are just more Neanderthal.’ We’ve found that autistic people, on average, have more rare Neanderthal variants, not that they have more Neanderthal DNA in general."
In contrast to the rare variants, the study found that common Neanderthal-derived variants were less prevalent in Black non-Hispanic and white Hispanic autistic individuals compared to controls. This finding was not observed in white non-Hispanic autistic individuals.
Clinical Associations: Beyond Autism
The researchers also identified specific clinical associations between Neanderthal-derived variants and autism-related traits. For example, a particular SNP (rs112406029) in the SLC37A1 gene was significantly associated with epilepsy in white non-Hispanic autistic individuals. Similar associations were found in other ethnic groups, linking certain Neanderthal variants to traits such as intellectual disability, language delay, and language regression.
Implications and Future Research
Casanova noted,
"I was rather surprised that many of the Neanderthal-derived variants we found that were associated with autism dramatically varied by ethnic group. It suggests that our tendency to 'whitewash' genetics and ignore variants that aren’t implicated across all genetic backgrounds means that we’re missing out on a lot of 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 have shaped neurodevelopmental conditions.
“In this current study, we only investigated the parts of the genome that contain protein-coding genes (known as the exome),” Casanova noted. “In the next phase, we plan on looking at the entire genome, since there’s a lot of interesting regulatory material that’s contained in those regions that’s undoubtedly influencing when and how genes are expressed. We also plan on including the Denisovan genome in our next phase of study to see if that DNA may be playing roles in autism in people with Asian/Native American backgrounds.”
Conclusion: A Complex Genetic Picture
The study, “Enrichment of a subset of Neanderthal polymorphisms in autistic probands and siblings,” by Rini Pauly, Layla Johnson, F. Alex Feltus, and Emily L. Casanova, presents a nuanced view of the relationship between Neanderthal DNA and autism. While identifying these susceptibility factors may help build a fuller picture of autism and its complex roots, this knowledge cannot be used for eugenics or similar agendas.
As Casanova pointed out,
"Some people in the autistic community get uncomfortable with genetics studies, in part, due to fears related to eugenics. But these Neanderthal-derived variants are also occurring in people, especially family members, without autism. So, while identifying these susceptibility factors may help us understand autism better, it does not imply a straightforward path to eugenics."
This research underscores the importance of considering genetic diversity and evolutionary history in the study of neurodevelopmental conditions, offering new insights into how our ancient heritage continues to shape modern human health.
Pauly, R., Johnson, L., Feltus, F. A., & Casanova, E. L. (2024). Enrichment of a subset of Neanderthal polymorphisms in autistic probands and siblings. Molecular Psychiatry, 1–10. https://doi.org/10.1038/s41380-024-02593-7