The genetic mutations that have been studied the most are those that have been linked to human disease, but what about mutations that provide some benefit? Researchers have now identified mutations that can do both. Cone-rod dystrophy refers to a group of disorders that impact the retina, and can lead to blindness. Patients also often have above-average intelligence. This disorder can be caused by mutations in a few different genes, including one called Rab3-interacting molecule 1, RIM1. In new research reported in Brain, scientists modeled that mutation in the fruit fly, an organism which has many genes in common with humans. The researchers determined that the mutation was actually improving the function of synapses, the points at which neurons connect and communicate with one another.
Mutations that disrupt synaptic proteins would typically be expected to impair brain function, but not in this case. “It’s very rare for a mutation to lead to improvement rather than loss of function,” said Professor Tobias Langenhan of Leipzig University.
The researchers showed that the normal fly version of RIM1 functions like the human version does. Then they introduced human mutations into the fly protein to study the effects. They used electrophysiology tools to measure synaptic activity in the flies carrying RIM1 mutations.
“We actually observed that the animals with the mutation showed a much increased transmission of information at the synapses. This amazing effect on the fly synapses is probably found in the same or a similar way in human patients, and could explain their increased cognitive performance, but also their blindness,” added Langenhan.
Additional work revealed that the mutation brings the molecular components that are involved in synaptic transmissions closer together. More neurotransmitters were released at mutant synapses, revealing how the mutation can accelerate neural impulses.
Super-resolution microscopy enabled the researchers to analyze individual molecules, even counting them to confirm that they are more closely aggregated than usual, said Langenhan.
About 75 percent of the genes that are related to human disease are also carried by fruit flies, noted Langenhan, who is planning additional work with colleagues to continue to model disease-associated mutations in the fruit fly.