Evolutionary brain changes may increase our susceptibility to worry

Our cognitive and emotional processes depend heavily on monoamine neurotransmitters like serotonin and dopamine. Their evolutionary ancestors were metazoans, and while related genes’ functions have remained mostly unchanged over time, genetic diversity within and between species has been found to significantly affect animal mental traits like sociality, aggression, anxiety, and depression.


The vesicular monoamine transporter 1 (VMAT1) gene, which transports neurotransmitters to secretory vesicles in neurons and secretory cells, has been revealed to have developed naturally during the development of humans by a research team led by Dr. Daiki Sato and Professor Masakado Kawata. In specifically, this gene’s 136th amino acid locus has changed from asparagine (Asn) to threonine (Thr) in the human lineage. In addition, a novel allele (isoleucine, Ile) has appeared and its frequencies have increased globally. It has been reported in the past that persons with the Ile genotype are less likely than those with the Thr genotype to experience sadness and anxiety, but it is still unclear how these human-specific mutations affect the brain and affect neuropsychiatric behaviour.

In this study, Sato, Kawata, Yukiko U. Inoue, and their colleagues created Vmat1 gene-edited mice in which the 136th amino acid locus was replaced with the human genotype (Thr or Ile) using genome editing technology. They then compared gene expression, neural activity, and behaviour between genotypes. The Ile-type mice displayed fewer anxiety-like behaviours, which is congruent with studies on people. The genotype also influenced neuronal activity and post-synaptic gene expression in the amygdala, a part of the brain involved in emotional regulation. This work could be the first step in understanding the molecular mechanisms underlying the VMAT1 gene’s functional significance in the central nervous system. Furthermore, there are just a few studies that have used genome editing technologies to confirm the consequences of single amino acid mutations under natural selection during human evolution.

With the goal of illuminating the pathogenic mechanisms behind neuropsychiatric diseases including anxiety and depression, this work highlights the functional significance of human-specific variations in the regulatory circuits of neurotransmitters involved in cognitive and emotional functioning.




Leave a Reply

error: Content is protected !!
Open chat
WhatsApp Now