Most of the chromosomes have been around for millions of years. However, researchers from the Stowers Institute for Medical Research have revealed new, very youthful chromosomal dynamics in fruit flies that are similar to chromosomes present in humans and associated with treatment-resistant cancer and infertility. Researchers say the findings could lead to the development of more targeted therapies to treat this condition.
A new study published in Current Biology reveals how this tiny chromosome that appeared less than 20 years ago survived in a laboratory-raised strain of fruit fly, Drosophila melanogasterand correlate with supernumerary (extra) chromosomes in humans.
“I feel like an astronomer watching the birth of a star,” said Stowers investigator Scott Hawley.
“We witnessed the birth of chromosomes and began to understand their capabilities and limitations.”
Previous research from Hawley Lab first identified these extra small chromosomes, but little was known about their shape, function, or dynamics during cell division. Stacey Hanlon, former Hawley Lab postdoctoral researcher, realized that this discovery could be an ideal system for investigating how new chromosomes arise, which could lead to methods for treating infertility and more effective cancer treatments.
Supernumerary chromosomes in humans are found in cancer cells and often interfere with drugs designed to target tumors, making these types of cancer, such as osteosarcoma, difficult to treat. In addition, the presence of supernumerary chromosomes in males can interfere with normal chromosomal segregation during sperm production, which can lead to infertility.
“Being able to understand how supernumerary chromosomes arise and what their structure is could potentially illuminate their vulnerability,” said Hawley.
“This could allow the development of potential therapeutic targets.”
Called the B chromosome – as opposed to the standard “A” set of essential chromosomes – this genetic element occurs naturally in the single laboratory stock of fruit flies in Hawley’s lab. Now, researchers are witnessing the birth and evolution of chromosomes in less than two decades.
“I like to call this B chromosome a genetic defector,” says Hanlon.
“They don’t follow the rules.”
Hanlon found that the fruit fly’s B chromosome is maintained by a mechanism called the “meiotic drive” that allows them to rebel against the usual rules of inheritance. The B chromosomes push their way to the next generation during egg formation to ensure their own persistence in more than half of the next generations.
“Their genetic background – meaning unique features in the fly genetic makeup of the B chromosome – favors their preferential transmission to the next generation,” says Hanlon.
“It gives these people evolutionary time to become a new chromosome, whether that’s taking an essential gene or acquiring something that allows them to cheat better.”
Importantly, the meiotic drive is a powerful force that can shape the way genomes evolve. This finding, coming from the Hawley Lab and being actively investigated by Hanlon, now in his own lab at the University of Connecticut, could be used to understand the mechanisms behind what keeps meiosis fair, and ensures that imposters like the B chromosome, don’t benefit. profit.
In addition, Hanlon is examining how specific mutations can lead to chromosomal breakage and the formation of new chromosomes, unraveling the mechanisms by which supernumeraries arise and become necessary components of a genome.
“We’re always looking for the Achilles heel to get rid of this kind of stuff,” Hawley said of the problem of supernumeraries in humans.
“If we can identify what drives their formation, we may be able to identify individuals who are more likely to form them and take better actions to seek and treat them.”