Neanderthal Autism: Could Ancient Genes Alter Brain Development?

Neanderthals and modern humans share a complex evolutionary history, with genetic traces of our ancient relatives still present in many people today. Researchers are investigating whether Neanderthal DNA influences neurodevelopmental conditions like autism.

Recent studies suggest that some genetic variants linked to brain development may have been inherited from Neanderthals. Understanding these connections could shed light on the biological foundations of autism and human cognition.

Neanderthal DNA In Modern Human Ancestry

Neanderthal DNA persists in modern human populations, with approximately 1–2% of the genome in non-African individuals originating from these archaic hominins. This inheritance stems from interbreeding events between 50,000 and 60,000 years ago, when anatomically modern humans migrated out of Africa and encountered Neanderthals in Eurasia. Advances in paleogenomics, particularly high-coverage sequencing of Neanderthal remains, have allowed researchers to pinpoint specific regions of the human genome that retain these ancient contributions.

Neanderthal-derived sequences are not randomly distributed across the genome. They are enriched in regions associated with skin physiology, immune function, and neurological traits, while notably absent from areas involved in male fertility—suggesting natural selection has retained or eliminated certain variants over time. The persistence of some Neanderthal alleles implies adaptive advantages, while the depletion of others indicates potential incompatibilities with modern human biology. This selective retention is particularly evident in genes linked to brain function, where some Neanderthal-derived variants have been associated with synaptic plasticity, neurotransmitter regulation, and cortical development.

One striking example is the presence of archaic alleles in NOVA1, which plays a role in alternative splicing of neural transcripts. A study in Science showed that introducing the Neanderthal version of NOVA1 into human brain organoids altered neuronal connectivity and differentiation patterns, suggesting these genetic differences influenced cognitive processing. Other Neanderthal-derived variants have been implicated in neurodevelopmental pathways, raising questions about their potential influence on conditions characterized by atypical brain wiring.

Genetic Variants Linked To Brain Development

The genetic architecture of brain development is shaped by a complex interplay of inherited variants that regulate neuronal formation, synaptic connectivity, and cortical organization. Some Neanderthal-derived alleles have been identified in loci associated with neurogenesis and brain plasticity, suggesting archaic DNA influenced cognitive evolution.

One example is FOXP2, a key regulator of speech and language development. While modern humans and Neanderthals share the same core FOXP2 sequence, surrounding regulatory elements inherited from Neanderthals may have subtly altered its expression, potentially impacting neural circuits involved in verbal communication.

Other Neanderthal-derived variants have been linked to neural progenitor cell proliferation and differentiation. Studies using induced pluripotent stem cells (iPSCs) suggest that archaic alleles in genes like PHLPP1, which modulates Akt signaling, influence neuronal survival and dendritic growth. Additionally, variations in genes regulating synaptic plasticity, such as those affecting glutamatergic signaling pathways, highlight potential distinctions in neural network structure between ancient populations and modern humans.

Genome-wide association studies (GWAS) have identified specific loci enriched for archaic alleles that correlate with altered gray matter volume in the prefrontal cortex, a region critical for executive function and social cognition. Single-cell RNA sequencing of human brain organoids carrying Neanderthal-derived variants has revealed differential gene expression patterns during early neurodevelopment, underscoring the lasting impact of these genetic contributions.

Mechanistic Insights On Potential Links To Autism

Neanderthal-derived genetic variants may influence conditions characterized by altered neural connectivity, such as autism. Autism spectrum disorder (ASD) is associated with atypical synaptic function, neuronal migration, and cortical organization. Some Neanderthal-introgressed sequences have been found in genes involved in axon guidance and synapse formation, processes frequently implicated in ASD-related neurodevelopmental differences. Variants affecting pathways such as SLIT-ROBO signaling, which regulates neuronal wiring, have demonstrated functional changes in connectivity patterns.

Functional genomic studies provide further insights into how these inherited variants shape brain function. Gene expression analyses in human brain organoids carrying Neanderthal-derived alleles have shown differences in neuronal differentiation timing, potentially influencing cortical layer formation. Delays or disruptions in these processes have been observed in ASD, where altered cortical thickness and connectivity are common findings. Additionally, electrophysiological recordings from neurons with archaic variants in genes regulating ion channel function have revealed changes in synaptic excitability, a characteristic often observed in ASD models.

Neuroimaging research has linked structural differences in brain regions associated with social cognition and sensory processing to archaic genetic variants. Studies using magnetic resonance imaging (MRI) have identified correlations between Neanderthal-derived polymorphisms and alterations in brain morphology, particularly in the temporal and frontal lobes—areas frequently implicated in ASD. These findings align with observations that some individuals with ASD exhibit differences in cortical folding patterns and regional connectivity, supporting the idea that ancient genetic contributions influenced neurodevelopmental diversity.

Observed Frequency Of Neanderthal Derived Polymorphisms

The distribution of Neanderthal-derived polymorphisms varies across human populations, reflecting historical admixture patterns and selective pressures. While individuals of non-African descent inherit approximately 1–2% of their genome from Neanderthals, the frequency of specific alleles differs due to genetic drift and regional adaptation. Some variants persist at relatively high frequencies, suggesting they conferred advantages, while others are found only in isolated genetic backgrounds, hinting at more neutral or mildly deleterious effects.

Genome-wide analyses have identified clusters of Neanderthal-introgressed loci enriched in genes linked to neurological function, though their prevalence is not uniform. A study in Molecular Biology and Evolution found certain archaic alleles associated with synaptic plasticity appear more frequently in East Asian populations than in European groups, possibly due to distinct selection pressures following early human migration. Haplotype analysis has revealed that some Neanderthal-derived polymorphisms exist in extended linkage disequilibrium blocks, indicating they may have been subject to positive selection or reduced recombination rates.

Correlation Studies In Neurodevelopment Research

Investigating the relationship between Neanderthal-derived genetic variants and autism spectrum disorder (ASD) requires genomics, neuroimaging, and behavioral analyses. Correlation studies have explored whether specific archaic alleles are associated with measurable neurodevelopmental traits, such as differences in brain structure or cognitive function. Large-scale genome-wide association studies (GWAS) have identified loci with Neanderthal ancestry that overlap with genes previously linked to ASD, suggesting a potential influence on neurodevelopmental variability.

Neuroimaging research supports a connection between archaic alleles and differences in brain morphology. MRI analyses show individuals carrying certain Neanderthal-derived variants exhibit subtle variations in cortical thickness and connectivity patterns, particularly in areas implicated in social cognition. Behavioral assessments have explored whether individuals with a higher proportion of Neanderthal-derived polymorphisms display traits associated with autism, such as differences in sensory processing or social interaction. While findings remain preliminary, they suggest some inherited alleles may contribute to variations in neural function that align with ASD traits, warranting further investigation.