The evolution of human cognitive abilities may have come with some disadvantages. A new study published on Aug 9 in the American Journal of Human Genetics suggests certain mental disorders may be linked to evolutionary changes (1). The researcher led by Dr David Kingsley, a professor of developmental biology at Stanford University School of Medicine, uncovered an unusually lengthy region of human-specific tandem repeats on the CACNA1C gene composed of 30 bp units, often repeated hundreds of times.
Kingsley and colleagues centred their attention on the CACNA1C gene, belonging to a family of genes responsible for calcium channels that control the flow of positively charged calcium ions into cells. Calcium ions play a key role in electrical signalling and therefore affect a number of functions including cell-cell communications, muscular contraction, as well as regulating other important genes. The gene has already been linked to mental disorders including schizophrenia, bipolar disorder, along with depression, anxiety, autism, and obsessive-compulsive disorder.
By looking at regions not involved in encoding for the protein ― “non-coding” parts ― the researchers came across an area that showed significant differences between the standard human genome based on various genomes collected as part of the 1,000 Genomes Project, a project carried out between 2008 and 2015 to create the largest public catalogue of international genotype data. The study showed that modifications of this particular region can increase or decrease the activity of the CACNA1C gene thereby affecting the risk of mental illness.
Even in the absence of genetic mutations, these repeated lengths of DNA ― found inside or outside the genetic coding sequences ― may explain the some of the variation in neurological functions among individuals. Different versions of highly repeated sequences can affect gene expression and decreased CACNA1C activity has been associated with increased risk of psychiatric diseases, moreover, the extent of gene expression can vary quite significantly across human DNA. Changes in the structure and sequence of these arrays are likely to have contributed to changes in CACNA1C function during human evolution thus modulating the neuropsychiatric disease risk in modern human populations.
According to Kingsley, many regions of the human genome are still largely unexplored, missing, or understudied, moreover, most studies focus on mutations in the DNA code ― simple letter substitutions ― however, large repeated regions may also contribute to individual phenotypic traits and susceptibilities to certain diseases. Physical conditions are often linked to evolution, for example, lower back pain is likely a result of the transition to walking upright and smaller, frequently impacted wisdom teeth may be tied to the recent shift in diet leading to a smaller human jaw size. This new study proposes a basis for neurological disorders in modern humans, which may have arisen from recent evolutionary changes in genes controlling the various aspects of brain function.
More than 3 percent of the global population is affected by bipolar disorder and schizophrenia. This study may provide some clues for the future treatment of these terrible illnesses and new hope for those suffering from the array of mental disorders plaguing modern society.
(1) Song JHT, Lowe CB, and Kingsley DM. Characterization of a Human-Specific Tandem Repeat Associated with Bipolar Disorder and Schizophrenia. The American Journal of Human Genetics (2018). DOI: 10.1016/j.ajhg.2018.07.011