Dynamics of an Additional Chromosome in Fruit Flies Uncovered by Scientists

Most chromosomes have been around for millions of years. Now, researchers from the Stures Institute for Medical Research have revealed the dynamics of a very new chromosome in fruit flies that is similar to chromosomes that originate in humans and are associated with cancer resistance and infertility. The findings may one day lead to the development of more targeted therapies to treat these conditions.

A new study published in Current Biology On May 4, 2023, he reveals how this tiny chromosome that arose less than 20 years ago persisted in a single, lab-bred strain of fruit fly, Drosophila melanogaster, and is associated with extra (extra) chromosomes in humans.

“I feel like an astronomer watching the birth of a star,” said Scott Hawley, a Storrs researcher, Ph.D. “We are watching the birth of the chromosome and beginning to understand both its capabilities and its limitations.”

previous search of Hawley Lab had first identified these extra small chromosomes, but little was known about their form, function, or dynamics during cell division. Former Hawley Lab postdoctoral researcher Stacy Hanlon knew this discovery could be an ideal system for investigating how new chromosomes come to life, which could lead to more effective cancer treatments and ways to overcome infertility.

Extra chromosomes in humans are found in cancer cells and often interfere with drugs designed to target tumors, making these types of cancers, such as osteosarcoma, difficult to treat. In addition, the presence of extra chromosomes in men can disrupt the normal segregation of chromosomes during sperm production, which can cause infertility.

“Being able to understand how extra chromosomes arose and what their structure is can illuminate their weaknesses,” Holly said. “This may enable the development of potential therapeutic targets.”

Called B chromosomes—as opposed to the standard “A” set of base chromosomes—these genetic elements appeared naturally in one laboratory stock of fruit flies in Hawley’s lab. Now, researchers are witnessing the birth and evolution of chromosomes in less than two decades.

How does something like this new chromosome emerge from nothing? More importantly, since the newly born B chromosomes do not possess any known essential genes for Drosophila function, how do they persist in the genome? In short, by cheating.

“I like to call these B chromosomes genetic bouncers,” Hanlon said. “They don’t follow the rules.”

Hanlon discovered that Drosophila B chromosomes are maintained by a mechanism called “meiotic drive” that enables them to rebel against the usual rules of heredity. The B chromosomes make their way to the next generation during the formation of the egg to ensure that they persist in more than half of the next generation.

“Their genetic background—meaning unique features in the genetic makeup of the flies’ B chromosome—supports their preferential transmission to the next generation,” Hanlon said. “This buys these guys evolutionary time to become a new chromosome, whether that’s picking up an essential gene or gaining something that enables them to cheat better.”

Importantly, meiotic drive is a powerful force that can shape how the genome evolves. These findings, which originated in the Hawley Lab and are actively investigated by Hanlon, now in her own lab at the University of Connecticut, can be used to understand the mechanisms behind what keeps meiosis fair and ensures that cheaters, such as B chromosomes, don’t thrive.

In addition, Hanlon studies how specific mutations can lead to chromosome breakage and formation of a new chromosome, revealing the mechanism by which supernumeraries arise and become necessary components of the genome.

“We’re always looking for the Achilles’ heel to get rid of these kinds of things,” Hawley said of the problematic overnose in humans. “If we can determine what encouraged their formation, we may be able to identify the individuals most likely to form them and take better measures to search for and deal with them.”