For those of you who have “been around the block” in the online autistic community, you’ve probably heard of the “Neanderthal Theory of Autism,” proposed by rdos (Leif Ekblad) back in 2001, along with the subsequent Aspie Quiz he designed, which was used, in part, to further explore these ideas. Back in my early days on Wrong Planet (WP) circa 2004-ish when I went by the handle, Sophist, I remember the numerous discussions on the topic. From my perspective, many auties found the idea appealing– in the same way that the alien logo of WP plucked a primal string amongst Aspergians who had frequently taken the brunt of bullying or, at the very least, ostricism and “otherness” throughout their lives. The idea of being more Neanderthal was perhaps appealing to some on the spectrum.
In those days, I will admit, I thought the Neanderthal Theory unfounded and a bit ludicrous (sorry, Leif!). And while I still don’t prefer to venture into hypotheticals about Neanderthal-like behaviors in modern people, my own recent research has led me down an unexpected path regarding the roles of ancient Neanderthal DNA in autism susceptibility. After reading The Pattern Seekers by Simon Baron-Cohen, in which he draws attention to something called the Upper Paleolithic Revolution, which began roughly 50,000 years ago and is purportedly an early intellectual renaissance in our species (at least within Europe), I found it interesting that this “renaissance” roughly coincided with the time periods in which early Eurasian people would have been hybridizing with Neanderthals. It made me wonder: Has Neanderthal DNA played an important role in our own intellectual evolution? Given the links between autism, savantism, creativity, and even genius, could it still be playing a role in autism today??? All of a sudden, the Neanderthal Theory maybe didn’t sound so ludicrous.
After gathering my thoughts into a testable hypothesis, I brought the idea to my collaborator, Dr. Alex Feltus at Clemson University. Thankfully, Alex is usually game for slightly wacky ideas provided they’re testable and the research man power is available, so we started planning our approach. It took awhile for us to get our scientific ducks in a row, but fast forward to summer 2023 when we had our first results. It turns out, not that autistic folks have more Neanderthal DNA overall, but that they have more Neanderthal variants that are otherwise rare in the general population. We’ve just published our results in the journal of Molecular Psychiatry, and have a series of future studies in the works, also expanding our research to include Denisovan DNA (another of our ancient cousins with whom early Asian people intermixed) [link to Open Access article].
People on the spectrum also seem to have more of a subset of common SNPs (SNPs that occur in at least 1% or more of the general population). In particular, we studied SNPs that are known as “quantitative trait loci” or “QTLs.” A QTL is any SNP in the genome that, when it varies or changes, it results in a measurable effect on a gene’s expression. For this study, we specifically only looked at QTLs that influence gene expression in the brain. A notable example includes a SNP in the SLC37A1 gene, which we found is associated with epilepsy and multiplex standing (i.e., more than one person in the family has autism). In particular, sixty-seven percent of white non-Hispanic autistics who were multiplex and had epilepsy carried this variant compared to 22% of ethnically-matched controls. Interestingly, SNP associations typically differed by ethnic group, so the same SNPs don’t appear to be susceptibility factors across all ethnic backgrounds. That means that the ethnic background of the person is also playing an important role, which has a lot of implications for genetics research in general.
What does this all mean? First off, I want to stress that autistic people are not “more Neanderthal” than non-autistic people. True, our original hypothesis predicted that autistic people, on average, would have more Neanderthal-derived SNPs than non-autistic people based on earlier work by Gregory and colleagues (2017). But this hypothesis wasn’t supported by the data. Instead, the reality is far more nuanced than that.
How Do Mutations Actually Work?
Most of us have grown up with the (false) idea that there’s a gene for everything: a gene for blue eyes, multiple genes for height, and even “autism genes.” But biology is never so simple. These are human generalizations that are akin to slapping a Campbell’s soup label on what are very complex processes. Individual genes are used as templates to create a variety of gene products (RNA, proteins) and variations in these genes and their products can definitely have a measurable influence on phenotype (observable characteristics). But the behavior of most genes is complicated and influences the behavior of numerous– if not all– cells in your body at one time or another. It’s important to understand this distinction in order to better appreciate what some Neanderthal SNPs may actually be doing in autism and how those effects can vary across different human populations.
Let’s imagine an extremely simplified example using two imaginary genes. We’ll call them Genes A and B. Genes A and B are next door neighbors to each other on Chromosome C. These A and B genes are often expressed at the same time, largely because the A and B proteins that ultimately get produced from these gene templates bind together to form the AAB complex, which contains two parts A to every B. Now, let’s pretend that the AAB complex is important in the development of neurons. You can start to imagine that the ratios at which Genes A and B are expressed are really important because if we produce too little or too much of either gene, that’s going to mess up that delicate balance and you won’t be able to make as much of the AAB complex, which might affect how your neurons develop.
Let’s say we reduce the expression of Gene A by 1/6th (figure below). This will lead to a 1/3rd reduction in the amount of the AAB complex we can produce in order to support neuron growth and development. In essence, our AAB complex is unbalanced. Because of this tendency to easily get off-balanced, Genes A and B are really sensitive to mutations and they don’t tend to tolerate them well. As a result, evolution of Genes A and B are relatively slow compared to other genes that are more tolerant of change. A lot of neurodevelopmental genes share this mutation sensitivity.
Now, a lot of genetic variants occur and are retained– not because they have some obvious positive adaptive benefit, like creating a new feature the lineage never had before. Instead, they tend to compensate for previous mutations that were not so beneficial (see Ohto, 1992). Basically, it’s a Red Queen genetic race where mutations occur and are retained because they help maintain (or re-attain) the status quo. However, when genetic variants are split apart that are normally used to compensating for each other, as may occur with sexual recombination in sex cells where we receive a mishmosh of our grandparents’ DNA, this can uncover individual mutations that lead to imbalance. This often happens in the case of two species when they hybridize, because unfamiliar variants can suddenly get thrown together and unbalance delicate networks like our imaginary AAB complex. In the illustration below, you can see how this plays out with the AAB complex when Homo sapiens and Neanderthals intermix, creating a hybrid offspring whose A and B gene expressions are out of balance with each other. This may have unanticipated effects on neuron development in the hybrid, even though we don’t see similar issues in either of the parents. Hopefully, you can appreciate that this scenario is more nuanced than simply saying, “Gene A is the gene for neuron development.” Otherwise, we lose context and, ultimately, understanding of the biological process that regulates the maturation of neurons.
In the early days following hybridization, we find that a subset of genetic variants that are spliced together thanks to sexual recombination reeeeaaaallllyy don’t work well together and these combinations are pretty quickly deleted from the gene pool, usually because they’re either lethal or they seriously affect fertility somehow. This most likely happened very early on when we began intermixing with Neanderthals. Eventually, however, Neanderthals went extinct (whether it was through competition, infection, or they got absorbed into our own larger species), such that we were left only with our new hybrid mostly-Homo-sapiens-plus-a-little-bit-Neanderthal species. Once the nasty SNPs got weeded out in the early days, that left a subset of variants that weren’t necessarily deadly or that impaired fertility, but they were just a little bit bad. Those SNPs, which are probably mildly mismatched with the H. sapiens background, are still being pushed out of the population genome, slowly and little by little.
These are probably some of the rare SNPs we’re seeing associated with autism. And while they’re likely being selected against because they’re mismatched with our ancestral genome and have some negative effects (e.g., health issues like immune disorders, connective tissue disorders, mild fertility issues such as PCOS), there’s also the possibility they’re simultaneously maintained in small numbers because they provide some benefit as well (e.g., human intelligence, creativity, etc.). This last bit is of course all conjecture and is not particularly testable, but these queries are nevertheless what led me to ask the question in the first place: Is Neanderthal DNA playing a role in autism susceptibility? Regardless of the reason some of these SNPs are sticking around in a subset of people, the answer appears to be “yes.” Even though this hybridization took place tends of thousands of years ago, it’s still playing a role in autism today.
Wow. Just… wow.
Science Over a Cuppa 
The deafening silence about the raging epidemic of autism is troubling: the CDC documented the prevalence of autism at 1:2500 in 1980 and 1:36 in 2020 (the latest statistics). Unfortunately, this 7,000% increase in autism is not addressed with alarm by the medical science community in defense of vaccines and “neurodiversity.” This is problematic because epidemics are caused by environmental factors and autism research is focused on genetics. Isn’t the silence around the raging autism spectrum disorder epidemic a crime against our children?
I definitely don’t decry doing studies into environmental stressors and there are labs that do that, such as Irva Hertz-Picciotto’s. But genetics is a component of susceptibility and that’s more the component that I study (as well as research related to Ehlers-Danlos and autism). But the stuff we’re studying is just one piece of a bigger puzzle. It’s complicated.
I’m contending that autism is caused by stress interfering with learning; the Irva Hertz-Picciotto Lab does not address stress as an environmental hazard.
Children are eminently motivated to learn about their environment to understand it, but learning material must have personal relevance. If learning material does not have personal relevance, children (and adults alike) will not learn.
Prior to 1980, childhood learning was far less competitive; children learned through modeling while their parents worked. Childhood learning environments are increasingly stressful consistent with the increased stress in the community. Children learn at different rates; any slower pace of learning in any area at any stage of development is now pathologized.
Childhood learning environments are problematic with too much instruction and correction about material unrelated to the stress in children’s lives (or simply unrelated to their personal interests).
Regardless, doesn’t a 7,000% increase in the prevalence of autism define a raging epidemic that deserves to be addressed with alarm by the medical community?
I’m not sure I would entirely agree with you. But that’s okay, we don’t have to agree. I can appreciate your points, however. I am definitely concerned about changes to the educational system and worry how that influences kids’ potential.
So if I were the above commenter, I’d want an answer from Emily Casanova, not me. : )
I’ll leave a thought on a somewhat related subject. It’s my layperson’s understanding that much of behavior and experience relates to how a person’s genetics interact with environment. So many investigations don’t fall into a strict either/or when it comes to addressing genetics/environment.
Yes, it is very complicated. And the genetics we’re reporting on in this paper are going to be weak susceptibility factors. So, there is definitely room for environmental stressors. Epidemics are definitely more than just environment. Some people are more susceptible, others less. No different here.
As I understand it, one hope is that susceptibility factors, weak as well as stronger ones, may teach us more about the conditions.
Sorry to leave two copies of my comment. Hopefully, it’s easy to delete one from your end. : )
So if I were the previous commenter, I’d want an answer from Emily Casanova, not me. : )
I’ll leave a thought on a somewhat related subject. It’s my layperson’s understanding that much of behavior and experience relates to how a person’s genetics interact with environment. So many investigations don’t fall into a strict either/or when it comes to addressing genetics/environment.
Several years ago, on the EDS Inspire Community Forum, a member proposed the idea that those of us with EDS might have more Neanderthal DNA than the rest of the population. Some of us who had done 23andMe DNA testing then shared our percentages of Neanderthal DNA. I’m going to have to go back and search for that post—to see if any conclusions were reached as a result of our informal, non-scientific poll.
Do we know what percentage of EDSers have autism?
Sadly no. But I’d really love to get my hands on the genetic data that TEDS collected. I really hope that’s made available to other researchers in future.
My father had a tomboy daughter and my brother and I, her siblings, each have a tomboy daughter. My wife’s paternal side featured many maiden aunts in the family tree, past and still alive, which is usually code for tomboy. Tomboys are female Aspies who want to be one of the guys at school but then there is the Margaret Thatcher style of female Aspie, having an unyielding iron will not interested in hanging out with boys per se but in beating them at their own game, Greta Thunberg being another. My wife has an ‘Iron Lady’ sister plus at least one brother was on the spectrum (whose spirit the sister crushed), and her son is on the spectrum. We have another daughter not on the spectrum but one of her sons is, the other two seemingly not. They are not the only people on the spectrum with whom I have had interactions either.
From this anecdotal experience I would conclude there is a genetic factor in autism altho there may be environmental factors as well, at least as to its manifestation e.g. diet can be a factor with modern processed foods as many cases of addressing diet back to old style diets seems to assist. Then we have cases where vaccines seem to bring on autism overnight, not the Aspie kind but mainline autism. And doesn’t, or didn’t, Prof Baron-Cohen hold out for regarding Asperger’s as being a different condition from Autism even if Hans Asperger had noticed the similarity, and merging the two makes for an easier diagnosis? Thus allow me to use ‘Aspie’ and ‘Aspergers’.
Observationally the usual ‘social cue’ and ‘small talk’ deficiencies taken to signify Asperger’s seem to me to be very superficial as it begs the question as to what purpose these serve. That I suggest is the building of Relationship to form the bridge on which NT folk interact. Aspies don’t interact relationally but transactionally. NTs can so interact, e.g. at the supermarket checkout but even there will go through a modicum of Relationship building, investing the time and effort even if not real interested.
This takes us one step backwards to what Asperger’s represents, in my experience, and that it is a different sense of Self than what NTs have, which has Self but also Other. Self is the sense that life comes into being as one’s own. Aspies have this and NTs do but NTs have an awareness that Other has their ‘own’ as well with Boundary limiting one’s ‘own’ self and Boundary limiting Other’s ‘own’ self and Relationship being the bridge that connects the two piercing the boundaries to enable interaction in a mutually reciprocal manner. Self’s ‘own’ is still at the centre but it is at the centre of a local neighbourhood, not a universal one and NT folk understand this. On the contrary it is known, to a greater or lesser degree, that Aspies have a much less developed sense of Boundary, particularly or Other’s Boundary. Thus they will interact transactionally as a uni-directional imposition of their Will onto Other, according to the Aspie’s Understanding of how things ought to be, with the Other seen as a bunch of Non Player Characters in the game of life like dodgem cars in sideshow alley. Margaret Thatcher epitomised this aspect of Asperger’s noting that to her “there is no such thing as society” was the truth.
Which leads to the fundamental observation that in Aspie consciousness the Faculty of Will is fused with the Faculty of Understanding. Will can change but only if Understanding is changed and Will has to be open to allowing this to happen.
Which brings me to Neanderthals. In Neanderthals the occipital bun brain supported a fused Will and Understanding. This was as it should be in the infancy of human consciousness when everyone was on the same page as to Understanding of the purpose of life, to Love, and thus everyone had the same Will, to Love. In time however a sense of one being the source of one’s own life came to the fore of Neanderthal consciousness and individual Understandings of Life emerged and thus so did Wills. Inevitably over the many millenia this led to conflict with no way to resolve it by a meeting of minds and compromise. My ‘Iron Lady’ sister-in-law had rejected the father of her son’s proposal as not being of the right form and she brought her son up herself. When conflict arose between these two Aspies she resolved it by thrashing him on the legs with a rubber flip-flop until her way prevailed. In Neanderthal times this degeneration of society due to the Neanderthal mind and brain’s shortcomings led to collapse and they disappeared, a development told in the Flood mythologies.
Having mentioned the mythology of archaic times I shall drop in reference to the Tree of Life as representing the idyllic days of shared childhood innocence and the Tree of Knowledge of Good and Evil desired by Ego(Eve) as representing the beginnings of divergence of Understanding.
The Ark with all its compartments and levels represents the new mind that enabled Noah, modern man who came from Neanderthals, and the frontal cortex combined with reduction in occipital bun enables the brain to support Self’s Understanding decoupled from Self’s Will, able to rise above Self Will and couple with the Other’s Understanding, enabling a meeting of Understandings of Self and Other and then a compromise / consensus developing to be taken up by the Will of Self and Other.
And in the mythology suggested the observation is that the Neanderthal brain and mind, aspects of which live on in Aspies, was unsuited to the support the emergence of Egoic bound individuals thus it vanished, and the modern human brain, which can deal with Ego, by recognising Boundary, emerged.
It is the fused Will/Understanding common to Aspies and Neanderthals that is the real linkage in my opinion.
This observation bears on the earlier comment that noted the ballooning of stress correlated with a ballooning of autism diagnoses but will not attempt to tease out this dynamic here having already gone on too long.
PS. Pain sensitivity is often mentioned as a Neanderthal characteristic inherited by Modern humans. It is well known that Aspies have particular sensitivity to pain or rough clothing for example, and hard mattresses. Another feature linked to Neanderthal genetics is red hair. Dentists are taught that a red haired person will on average need 1/6th more local anaesthesia to achieve the pain numbing effect that other hair coloured people typically require.
Interesting exploration of ideas! 🙂