A “super-Mendelian” toolkit
Active genetic elements that change the rules of genetic inheritance could have broad applications.
Gregor Mendel was an Austrian monk and botanist whose work with pea plants in the 19th century founded the field of genetics. Though he was not aware of genes at the time, Mendel essentially worked out that pea plants had two copies of each gene, and that each copy had a 50% chance of being passed on to any one offspring. Yet not all genes actually follow this pattern of inheritance.
In 2015, researchers reported that they had used components of the CRISPR/Cas9 genome editing system to edit genes so that they could propagate in a “super-Mendelian” fashion. Indeed, when it was engineered into fruit flies, any parent carrying this active genetic element passed it on to almost every offspring. Active genetic elements have potential applications in many different fields of scientific research. These include providing new ways to explore how genes control the formation and activity of different organisms.
Now, Xu, Gantz et al. — including the two researchers involved in the 2015 work — have used a new active genetic element called a CopyCat element and more traditional genome editing to analyze the control of a gene that coordinates the formation of a simple structure in a fruit fly — a vein in the wing. The goal was to understand which sections of DNA controlled where and when genes are activated to result in this structure being reliably located in its correct position.
First, Xu, Gantz et al. used genome editing to make mutations in a stretch of DNA that regulates the gene involved in wing vein formation. The effects of these mutations unexpectedly suggested that pairs of chromosomes might be interacting to control the activity of this gene. This was something that had not been seen before, which shows the advantage of editing a gene’s regulatory sequence at its normal location within the genome.
Next, Xu, Gantz et al. used the CopyCat tool to delete the regulatory sequence and replace it with sequences from three other species of flies. When the sequence was replaced with that of a housefly, a complete vein formed but it was further forward than normal for a fruit fly, and more closely matched the position of the wing vein in a housefly. These findings show how gene activity can affect the position of a simple structure; they also suggest that this strategy could help scientists to understand how the genomes of different species have evolved.
Xu, Gantz et al. hope these advances will encourage other researchers to use active genetic elements in a broad range of organisms to enable and accelerate their research. Since these tools fundamentally change the rules of genetic inheritance, they have many applications beyond research too. These applications are not without their risks and would need careful consideration, but could include engineering wild mosquito populations to combat diseases like malaria, dengue fever, chikungunya and Zika.
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