First published: 21 August 2018
Maintenance of genetic variants susceptible to psychiatric disorders is one of the intriguing evolutionary enigmas. The present study detects three psychiatric disorder‐relevant genes (CLSTN2, FAT1, and SLC18A1) that have been under positive selection during the human evolution. In particular, SLC18A1 (vesicular monoamine transporter 1; VMAT1) gene has a human‐unique variant (rs1390938, Thr136Ile), which is associated with bipolar disorders and/or the anxiety‐related personality traits. 136Ile shows relatively high (20–61%) frequency in non‐African populations, and Tajima’s D reports a significant peak around the Thr136Ile site, suggesting that this polymorphism has been positively maintained by balancing selection in non‐African populations. Moreover, Coalescent simulations predict that 136Ile originated around 100,000 years ago, the time being generally associated with the Out‐of‐Africa migration of modern humans. Our study sheds new light on a gene in monoamine pathway as a strong candidate contributing to human‐unique psychological traits.
A question as to how human‐unique characteristics have been evolved is of broad interest to biologist and the general public. To cope with this question, we focused on genes relevant to psychiatric disorders, since it has been hypothesized that the emergence of psychiatric disorders is linked to the evolution of human brain. On the other hand, most genetic variants susceptible to psychiatric disorders have relatively moderate effects and serve as a foundation of personality traits. Although there are some previous studies that aimed to detect psychiatric disorder‐relevant genes under positive selection in the human lineage, human‐unique genetic variants maintained by selection have not been explored. Such genetic variants could associate with human‐unique mental variation, such as personality traits. Here, we found a gene, SLC18A1 (VMAT1: Vesicular monoamine transporter 1), as a positively selected gene in the human lineage. This gene has a human‐unique variant (Thr136Ile; different from other mammals (136Asn)) whose association with several psychotic symptoms has been repeatedly indicated. Moreover, our analysis showed that this variant has been maintained in non‐African populations by balancing selection and had originated around 100,000 years ago, typically regarded as the timing of Out‐of‐Africa migration. 136Thr has been indicated to be associated with depression and anxiety compared to 136Ile, thus it could be possible that tendency to feel uneasy have been selected during human evolution and that environmental changes accompanied with Out‐of‐Africa migration resulted in the selective advantage of 136Ile against such anxious minds, sometimes leading to psychiatric disorders. This study is the first to provide evidence that a certain sort of psychological traits in humans has been adaptively selected and that diversity of personality traits, possibly leading to psychiatric disorders, are maintained by balancing selection in the current populations.