Positive and balancing selection on SLC18A1 gene associated with psychiatric disorders and human-unique personality traits

Abstract

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.