Humans gained many new traits over the course of our evolution. However, not all of them were beneficial. New research identifies genes linked with schizophrenia and autism that developed over the course of human evolution. In fact, they may have appeared late in the game; with these genes missing from our closest relatives like the Denisovans and Neanderthals.
That’s not to say our species specifically evolved to get these conditions. Rather, it appears that our evolution created a vulnerability to them. Subsequent mutations broke these vulnerable sections of our genetic code, producing these conditions.
HAR-dy HAR-dy HAR
The root of these issues is a part of your genome called the “human accelerated region”. Also labeled the “HAR” by lazy researchers. The HAR is notable for being what makes humans special.
Many species – including humans – share huge stretches of our genetic code. This “conserved genes” are the basic building blocks for complex life. Even a minor change to them can be lethal, preventing mutation and evolution changing them much between species. However, some of these conserved genes have changed a lot in humans. This is the HAR. Genes that have remained unchanged for millions of years, until humans came along and started tinkering with them.
The fact that the genes are so conserved in other species highlights their importance. Both for them, and us. After all, surely some of those unique genetic changes explain the unique physical changes humans have undergone. For example, HAR 1 is most expressed during the development of the brain in the womb. Given how special our brain is, this likely makes HAR 1 kind of a big deal.
However, the fact that these bits of the genome have been conserved for so long shows they can cause issues when changed. So the HAR is playing with fire. And sometimes we get burned. Huntington’s disease, for example, seems to be linked to HAR 1 going wrong.
Two new papers have identified a relationship between the HAR and both autism and schizophrenia. This suggests that these conditions might be linked to similar issues with the HAR.
Autism and evolution
The fact that the HAR is conserved in other species shows that these are parts of the genome vulnerable to change. Most are lethal, so little change is able to accumulate. The HAR also seems to have a similar vulnerability. It contains a lot less variation between people than expected. Much like these sections in non-humans, the HAR is conserved.
Nevertheless, some relatively “safe” differences can occur in the form of copy number variation (CNV). Some sections of our genome – including the HAR – repeat. The number times a section is repeated varies from person to person. This can have fairly major consequences for “dosage specific genes”. Some genes produce a protein or help something grow. So more copies of that gene can mean more protein or growth. Plus, sometimes the copies can mutate; having further effects.
An analysis of CNV in the HAR found 4 notable genes. They’re linked to neural function and are dosage dependent. And, crucially, have some CNV. Some degree of copy number variation seemed to alter their function. The result was those with CNV in these genes were more likely to develop autism spectrum disorder.
Ultimately, these CNVs ~5% of autism cases in the sample population studied. Whilst that might not seem like a huge amount, it’s worth noting that these researchers didn’t examine very known HAR region. Additionally, the sample population they examined only included siblings. Whilst this helped them produce reliable results, it could potentially underestimate the role of these CNVs.
Schizophrenia and evolution
Another paper examined a slightly wider section of the human genome. The HAR region is notable for being conserved in other species. These researchers were more curious about differences that had accumulated in our genome since we split with Neanderthals. If these differences overlapped genes linked to schizophrenia it would indicate the condition evolved relatively recently. Within the half a million years. And that it’s unique to our species.
Sure enough, they found an overlap between the two. So those two important conclusions were vindicated. Schizophrenia is a relatively recent development only our species has the privilege of encountering.
Many of these genes are linked to neurological development. Just like those HARs associated with autism. As such, it seems like a similar phenomenon is at play. Evolution tinkered with important genes to produce important changes. But in the process, those genes became vulnerable to further change. So when it inevitably happens, the results can be harmful to the individual.
Doan, R.N., Bae, B.I., Cubelos, B., Chang, C., Hossain, A.A., Al-Saad, S., Mukaddes, N.M., Oner, O., Al-Saffar, M., Balkhy, S. and Gascon, G.G., 2016. Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior. Cell, 167(2), pp.341-354.
Johnson R, Richter N, Jauch R, Gaughwin PM, Zuccato C, Cattaneo E, Stanton LW (2010). “The Human Accelerated Region 1 noncoding RNA is repressed by REST in Huntington’s disease.”. Physiol Genomics. 41 (3): 269
Srinivasan, S., Bettella, F., Mattingsdal, M., Wang, Y., Witoelar, A., Schork, A.J., Thompson, W.K., Zuber, V., Winsvold, B.S., Zwart, J.A. and Collier, D.A., 2015. Genetic markers of human evolution are enriched in schizophrenia. Biological psychiatry.