Our adventurous ancestors: global trends of DRD4 polymorphism

As a Psychology and Biology: Neuroscience double major, there is often more overlap between the classes I take in the two departments than some of my other double-major friends. However, in any given semester take classes as seemingly different and unrelated as Social Psychology and Molecular Biology. Because of this, I love the times when I find overlap between my classes and I can use information I learn in one department to help me understand a topic in a completely different class. This week that happened!

In our Psych & Neuro seminar we learned about a specific gene (DRD4) that encodes for a dopamine receptor that tends to make people more novelty-seeking and adventurous, and how the proportion of people with different variations of this gene varies widely between different populations around the world, and how it is theorized that evolutionary forces might have led to this variation between populations. In the Bio department, I am currently taking a course called Evolutionary Analysis, and throughout the semester we have been discussing various evolutionary forces and how traits can change in populations over time due to a variety of factors. Knowing what I know about genetics and evolution from Bio classes has helped me better understand this example of DRD4 variation that we studied in my Psych class. (I’ll do my best to avoid getting to bio-y in this post but there’s a lot to cover.)

First, DRD4 is a gene for the dopamine receptor, D4. There are many, many variants of this gene, but the most common ones are 2R, 4R and 7R. These different alleles vary in terms of how many repeats of a section of 48 base pairs of DNA are present in the gene (i.e. 7R equals this section is repeated 7 times in that person’s DNA). These differences in repeats basically has the effect of changing the structure of the protein that forms the receptor and makes the 7R variant less responsive to dopamine in the cortex. This causes people who carry the 7R gene to more often display traits like novelty-seeking, extroversion, and impulsivity. (I was going to try to find a diagram of the structures of different versions of the receptor to put here, but they were all so complicated that even I didn’t understand them, so I didn’t think it would be helpful.)

The receptor D4 is associated with a variety of psychiatric disorders such as ADHD, substance abuse, reactions to stress, and several personality traits, but the most interesting finding regarding DRD4 is the extreme differences in prevalence that occur in different human populations. A study conducted by Chang et al. in 1996 look at the genomes of 1,327 individuals and found that the frequencies of the 2R, 4R and 7R alleles were extremely different in different populations. The 4R allele is the most prevalent around the world with 64% of all humans having that allele, while 20% of humans have 7R and 8% have the 2R allele. However, when you look at populations in different regions of the globe, you find very interesting trends, specifically with regards to the 7R and 2R alleles. 48% of humans from North and South America were found to have the 7R allele, while only 2% of East and South Asians have it. In contrast, only 3% of people from the Americas have 2R, while 18% of people in Asia have it. That’s a huge difference.

So how did this happen? The fact that, while in varying proportions, each of these three alleles are found to exist in some amount in all populations around the world suggests that the mutations that caused these alleles occurred in ancient humans and existed when humans began to migrate out of Africa tens of thousands of years ago. This rules out the possibility that these alleles arose separately once humans had divided into separate populations in different regions of the world, which means that, in some sense, evolutionary forces must have led to the vastly different proportions observed in different populations.

One fascinating theory proposed by Chen et al. in 1999 suggests that migration patterns in prehistoric times played an important role on this distribution. They compared the genotypes of people from 39 different populations around the world (including Spaniards, Danes, Ashkenazi Jews, Cheyanne (US), Quechuan (Peru), Samoans, and Bantu (South Africa)). First, they looked at the effects of differences in ‘micro-migration’ by dividing the populations into two groups based on ‘settlement type’, either sedentary (societies that mostly used agriculture) or nomadic (i.e. foragers, herders, etc.). Nomadic societies had higher levels of the 7R allele (remember, it is associated with higher levels of novelty seeking and extraversion), which the authors suggested might have been selected for in these societies whose survival depended on exploration of new environments.

7R alleles and macro-migration patterns

Then, even more tellingly, they looked at trends in ‘macro-migration’. To do this, they estimated the distance in thousands of miles that each population would have had to travel from their original location using evidence from archaeology and historical linguistics. For example, macro-migration following the path of migration from Northern Asia to the Americas starts at zero with Asian populations whose ancestors crossed the land bridge between Asia and North America and continues to increase from Native American populations in North America to other indigenous populations in Central and South America. The graph on the right shows the positive correlation between macro-migration and long alleles (aka alleles with more repeats, like 7R) across all the populations studied. As the distance that that society’s ancestors would have travelled (slowly over thousands and thousands of years; obviously no single individual made the journey all the way from China to the south of Chile) increases, so does the proportion of individuals who carry the 7R allele. This theory suggests both that individuals who were more adventurous and novelty seeking were generally more likely to travel and push the migration of the population forward (which led to the populations that descended from them to have higher levels of the allele), and that this behavior was actively selected against in societies that have remained in their current locations for the past thousands of years. Specifically, many of these have relied on agriculture for a very, very long time, a system of getting food that requires more patience, less novelty seeking, and less desire to migrate than herding and foraging, making it socially and survivally undesirable to be novelty-seeking and making individuals who exhibited these traits less likely to survive and reproduce.

Migration patterns across the Bering Strait

When you think of traits that are affected by evolution, you probably think about Darwin’s finches, or fish crawling out of the ocean and starting to walk on land (the biologist in me has to point out that, of course, this is very oversimplified). You, like me, probably don’t think about human psychological traits being selected for over thousands of years and having a potentially dramatic influence on cultural practices and behaviors around the world. However, the results of these studies suggest that evolutionary forces can act on something as seemingly inconsequential as risk taking behaviors and have major impacts. For example, Asian cultures are almost always collectivist, while Western cultures are generally more individualistic, and some of this difference is likely due to the genetic makeup of the different populations. It makes sense that a group of people who are more often introverted and less interested in seeking new experiences because of their genetic makeup would then form more collectivist societies that value selflessness, working as a group, tradition, and unity. I found this entire phenomenon to be an extremely fascinating and unusual example at the intersection between my two areas of interest, psychology and biology.

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