Originally a staple in chaotic theory, the concept of the butterfly effect holds significant relevance in the development of autism spectrum disorder (ASD).
What Is the Butterfly Effect?
The butterfly effect describes the notion that the world is profoundly interconnected and that a small event can affect a larger complex system. It refers to an occurrence wherein a slight change in starting conditions can lead to vastly different results. The term was first coined by meteorologist Edward Lorenz, a mathematician at the Massachusetts Institute of Technology.
In 1961, Lorenz entered some numbers into a computer program that simulated weather patterns. He then left his office to get a cup of coffee, allowing the machine to run. When he returned, he noticed that the computer had simulated the weather for the next two months, but in a completely different way than what he had seen earlier.
From this unexpected result, Lorenz concluded that small natural changes can have large consequences. He suggested that the flap of a butterfly's wings can ultimately cause a tornado, at least hypothetically. Also known as "sensitive dependence on initial conditions," the butterfly effect suggests that forecasting the future can be nearly impossible.
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Complex Ripple Effect
At the RIKEN Center for Brain Science (CBS), researchers examined how the mutations in regions of the genome that help control gene activity can affect the development of ASD. The result of their study is discussed in the paper "Topologically associating domains define the impact of de novo promoter variants on autism spectrum disorder risk."
It is widely known that DNA contains promoters, the genetic materials that switch genes on and off. Since DNA molecules are twisted and coiled in a 3D configuration, promoters can control genes far from them in the DNA sequence. This means stretching the DNA would bring the promoters and genes further apart while introducing folds in the molecule would bring them closer together.
The combination of the promoter and the genes it controls form a regulatory unit known as a topologically associated domain (TAD). Due to this complex mechanism, an individual who does not have mutations in autism-linked genes can still develop ASD because of mutations in promoters.
While autism is highly heritable, it can also be caused by mutations that arise in DNA. These mutations are found in non-coding regions of DNA, a part of the sequence that includes promoters and does not contain instructions for building proteins. Until now, little is known about how mutations in non-coding DNA affect the likelihood of developing ASD.
To address this question, the CBS researchers analyzed the genomes of over 5,000 people with ASD. Led by Dr. Atsushi Takata, they used specialized techniques to capture the three-dimensional configuration and identify TAD boundaries around autism-linked genes.
The team discovered a direct link between ASD and TAD-related gene regulatory mechanisms, especially those that contain genes known to be associated with autism. This indicates that just a single base of DNA sequence difference in a non-protein-coding region can impact the expression of nearby genes. As a result, this leads to an increased risk of ASD.
Takata compared this phenomenon to the "butterfly effect," where a slight change in the initial state of a complex system can result in something with much larger consequences. Cellularly, a subtle mutation in a promoter can greatly affect gene expression elsewhere.
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