The ultimate theory on the evolution of neurodiversity: humans evolve at the level of the community

a proposal

The hypothesis that I am about to present occurred to me one night when I was walking home from lab. At the time, I was studying neurodevelopmental diseases for my PhD. This includes things like autism, schizophrenia, and ADHD. (I also studied obesity during my PhD work, which to a certain extent, can also be considered a neurodevelopmental disease, since brain genes are involved. I wrote about it here.)

Because of that work, I have good background knowledge about the genetics of neurodevelopmental disease, and I haven’t seen this specific hypothesis anywhere else in the literature (or books or popular media). I also asked ChatGPT if it’s seen it before, and it hasn’t, which is pretty cool. What you’re about to read can be found nowhere else.

Just a few more notes before I get to it.

• First, neurodevelopmental disorders are complex and both genetic and environmental factors contribute to these diseases. The genetic component can be further broken down into genetic variation that is common in the population and genetic variation that is rare in the population. Rare genetic variation is usually associated with more severe neurodevelopmental disease (think Down Syndrome or Rett’s Syndrome). Rare genetic variation is also usually newer in the gene pool, hasn’t been around as long, and hasn’t been subject to the kinds of evolutionary pressures that I will be talking about in this article.

• Second, I haven’t seen anything in the literature that outright refutes or disqualifies my hypothesis. And as you will see, it does make testable predictions.

• Third, this idea that I will very shortly convey to you falls neatly into the category of evolutionary psychology, and evolutionary psychology is a controversial field. It’s not my area of expertise, and I don’t really feel ready to address the criticisms around it. There are many, and I’m sure if I looked at them closely and thought deeply about them, I would agree with some criticisms and disagree with others, and to different degrees. The way I think about evolutionary psychology right now, is that psychology is a difficult field and people have trouble doing it with modern day humans (over 50% of psychology studies fail to replicate). Evolutionary psychology takes this difficult field and tries to apply it to the deep past, of which we know very little about. I will be doing a little bit of this today.

• Fourth, I like this hypothesis because of its beauty.

Enough with the caveats.

What the heck are you proposing?

Evolution doesn’t just happen at the level of the individual, but also at the level of the community. Communities are in direct competition with each other, and humans form much more complex communities than other animals. We have division of labor and social roles. We collaborate. If someone is especially good at (and has a preference for) one task, they’ll probably end up doing that task. If someone is especially bad at a task, they’ll probably end up doing something else.

I think you see where I’m going with this.

For a herd animal, like deer, each deer wants to be fast, to be able to notice and react quickly to threats, to be able find food and remember where the food is. (I am simplifying here, maybe deer have more complex social dynamics.) But overall, each deer needs to be good at pretty much all of the deer stuff.

Not so for humans. Let’s say that, in one of these communities, an individual is born with extra good color vision, and because of that they are better able to find forage, or identify a poisonous plant from an edible one. Not only does that individual benefit, but everyone in their community does as well.

The same idea holds true for other kinds of possible neurodiversity, like better night vision, better organizational skills, better storytelling ability, better memory. If one or a few people have any of these advantages, everybody benefits.

On the flip side, this also means that humans are more resilient than other mammals to different kinds of neurodevelopmental deficits. Let’s say someone has worse coordination—well, that individual doesn’t have to be involved in tasks that require high coordination. They can do something else.

Now, you can imagine that a new genetic variant is introduced into a community that confers both advantages and disadvantages. As a hypothetical example, let’s say a new variant is introduced that improves memory but reduces coordination. Humans are in a unique position compared to other animals to benefit from that variant.

Do neurodevelopmental diseases confer both advantages and disadvantages?

This part of the hypothesis isn’t new. It’s been suggested before that different neurodevelopmental diseases may confer some benefits to the individuals who have them (or to individuals who carry the risk variants).

Autism has long been associated with the engineering disciplines (the book neurotribes talks about this), and, in population studies, it’s been shown that common variants that associate with autism also associate with higher intelligence—which gives validity to that idea.

It’s also been suggested that schizophrenia may be helpful in building up religions, which in turn, may increase social cohesion within a group.

Interestingly, it’s even been hypothesized that colorblindness is helpful in seeing through camouflage. And colorblindness is much more prevalent in humans than in our close cousin primates who share a similar tricolor vision system.

If those things have already been proposed, how is this theory different than other neurodiversity theories?

All of the previous theories only consider the adaptation at the level of the individual, not the level of the community. This has an important implication on what types of genetic signatures we would expect to find in the human gene pool. There are different kinds of evolutionary selection, and they leave different traces in the genome…there’s positive selection, negative selection, and balancing selection.

Positive selection happens when a new beneficial variant is introduced into a population and increases in frequency until it reaches fixation at 100%. There tends to be less genetic variation around a variant that has undergone recent positive selection—because as the variant increases in frequency in the population it brings along the nearby variants with it. There are other signatures or patterns that researchers can look for, too.

Negative selection is the opposite. A detrimental variant is selected against until it is eliminated from the population. There are specific patterns to look for here.

Balancing selection, on the other hand, is when multiple variants are maintained within the population, and no single variant is favored completely over the others. There are three common reasons for balancing selection:

• Heterozygote advantage: having one copy of the variant is beneficial but having two copies is detrimental

• Frequency-dependent selection: the fitness conferred by the variant depends on the frequency that the variant is present in the population.

• Variation in time and space: the most beneficial variant changes depending on the environment.

I guess, it could be argued that what I’m proposing falls into frequency-dependent selection. I would argue it’s a bit more complicated than the kinds of frequency-dependent selection I’ve read about, and deserves it’s own name. I call it community-level selection. (It already has a name. It’s called inclusive fitness or kin selection. Thanks James Horton and Dogscratcher)

Regions that have undergone recent balancing selection usually are more diverse than other regions. However, I’ve also read that it is difficult to distinguish recent balancing selection from recent positive selection because the signatures can look similar.

The location in our genome that has the strongest signal for balancing selection is the major histocompatibility complex (MHC), which is involved in immune system function. It is also the region in our genome that has the most diversity.

If my hypothesis is correct, we would expect to see signatures of balancing selection and greater genetic variation in genes that have been implicated in neurodevelopmental disorders.

Are autism, schizophrenia, and ADHD genes under balancing selection?

This is the central prediction this hypothesis makes. To start, we can look at the available literature and do a simple test. Researchers have previously published lists of genes that are under balancing selection (based on genome wide scans), and other researchers have published lists of genes that have been implicated in autism (there’s about a thousand genes).

We can compare these two lists and ask the question, are these two lists independent of each other or related in some way? If the two lists are independent (for example, each list is a random selection of genes from the human genome), then we would expect X number of genes to appear on both lists. But if the real number of genes that appear on both lists is greater than X, then it supports the hypothesis these two lists are related (and rejects the null hypothesis that these two lists are independent).

It’s a pretty straight forward test. We can also get a p-value that tells us the probability that the null hypothesis is true. Anything less than a p-value < 0.05 is considered statistically significant in rejection of the null hypothesis and in support of the alternative hypothesis (the community-level selection hypothesis the inclusive fitness balancing selection hypothesis).

For this test, I chose to use the autism related genes listed in the SFARI database. And for a list of genes under balancing selection, I chose this paper by Bitarello et. al., which seemed good enough. (I’m not really familiar with genome wide scans of balancing selection.) I’ll leave more details of my exact methods in the comments.

The result I found was pretty surprising.

There were twice as many autism genes under balancing selection than expected by chance. Based on a statistical test, the null hypothesis is rejected with a p-value < 1 x 10^-15.

This is such a strong result, and I’m kind of worried that I did something wrong or overlooked something. I hope someone can chime in if I missed something.

When I started writing this piece I was planning to cite two pieces of preliminary evidence. The first: as I mentioned before, there are potential benefits for colorblindness for hunting, and color blindness is present in 8% of humans and rare in most Old World primates with a similar color vision system. The second: There are signs of balancing selection in the gene that encodes the red cone color receptor in humans but not in our close chimpanzee relatives. I wanted to focus on the color vision system because I thought it was more simple than neurodevelopmental disease, which are less well understood. The predictions the hypothesis made about the color vision system are simple, that it would more diverse in humans than in our primate relatives, and I thought that would be sufficient preliminary evidence to give some support to the hypothesis.

I did the enrichment test with autism genes and balancing selection genes out of curiosity, and was pleasantly surprised.

Overall, I see this as strong preliminary support for the theory of community-based inclusive fitness-based evolution of neurodiversity. This is first time, as far as I know, that such an overarching theory for neurodiversity has been proposed—that it evolved due to the unique social collaboration within human communities.