Cell & Microbiology

Researchers study the behavior of a fruit fly ‘extra’ chromosome.

The vast majority of chromosomes have existed for millions of years. Presently, scientists from the Stowers Foundation for Clinical Exploration have uncovered the elements of a new, exceptionally youthful chromosome in organic product flies that is like chromosomes that emerge in people and is related to therapy-safe malignant growth and barrenness. The findings may eventually lead to the development of more specific treatments for these conditions.

Another review distributed in Current Science on May 4, 2023, uncovers how this little chromosome that emerged a long time ago has endured in a solitary, lab-raised type of the organic product fly, Drosophila melanogaster, and is associated with exaggerated (extra) chromosomes in people.

“We are getting to watch the birth of a chromosome and are starting to understand both its capabilities and limitations,” Stowers Investigator Scott Hawley, Ph.D., said. “I feel kind of like an astronomer who’s watching the birth of a star.”

“It may be possible to identify a supernumerary chromosome’s vulnerabilities by knowing how it forms and what it looks like. This might make it possible to develop potential treatment targets.”

Stowers Investigator Scott Hawley, Ph.D.

These tiny extra chromosomes were first discovered by Hawley Lab research, but little was known about their form, function, or dynamics during cell division. Previous Hawley Lab Postdoctoral Specialist Stacey Hanlon, Ph.D., understood that this revelation could be an optimal framework to research how new chromosomes emerge, which might prompt more compelling malignant growth medicines and techniques to conquer barrenness.

Human supernumerary chromosomes are found in cancer cells and frequently prevent drugs designed to target tumors from working, making it difficult to treat cancers like osteosarcoma. In addition, men with supernumerary chromosomes can disrupt normal sperm production through chromosome segregation, which can result in infertility.

“Being able to understand how supernumerary chromosomes arise and what their structures are can potentially illuminate their vulnerabilities,” stated Hawley at the Stowers Institute for Medical Research. This might make it possible to identify potential therapeutic targets.”

These genetic elements, which Hawley’s lab refers to as “B chromosomes” as opposed to the conventional “A” set of essential chromosomes, were found naturally in a single laboratory stock of fruit flies. In less than two decades, the researchers are now witnessing the birth and evolution of chromosomes.

How does something that looks like this new chromosome come from nothing? More importantly, how do these newly born B chromosomes persist in a genome when they lack any known essential genes for fruit fly function? To put it plainly, by cheating

Hanlon stated, “I like to call these B chromosomes genetic renegades.” They disregard the regulations.”

Larva has 13 B chromosomes in addition to eight essential A chromosomes. DNA is stained with DAPI. Credit: Stowers Institute for Medical Research

Hanlon discovered at the Stowers Institute for Medical Research that the fruit fly B chromosomes are maintained by a mechanism known as “meiotic drive,” which allows them to defy inheritance rules. In order to guarantee their own persistence in more than half of the subsequent generations, the B chromosomes drive their way into the next generation during the egg’s formation.

According to Hanlon, “their genetic background—meaning the unique features in the genetic make-up of the B chromosome flies—supports their preferential transmission to the next generation.” That gives these guys time to evolve into a new chromosome, whether by acquiring an essential gene or something that makes it easier for them to cheat.

Importantly, meiotic drive is a potent force that has the power to influence the way genomes change. These findings, which came from the Hawley Lab and Hanlon, who is now working in her own lab at the University of Connecticut, has been actively looking into, can be used to learn how fair meiosis keeps cheaters like the B chromosomes from succeeding.

B chromosomes and Chromosome 4 highlighted in yellow using a special sequence recognition probe. Credit: Stowers Institute for Medical Research

Hanlon is also investigating the mechanism by which particular mutations cause chromosome breaking and the development of new chromosomes, demonstrating how supernumeraries emerge and transform into essential elements of a genome.

Hawley remarked, “We’re always looking for Achilles heels to get rid of these kinds of things,” referring to human supernumeraries that are problematic. We may be able to identify individuals more likely to form them and take better measures to look for and deal with them if we can determine what encouraged their formation.”

More information: Stacey L. Hanlon et al, B chromosomes reveal a female meiotic drive suppression system in Drosophila melanogaster, Current Biology (2023). DOI: 10.1016/j.cub.2023.04.028

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