Centromeres could be ‘hotspots’ for evolutionary innovation

Biologists at the University of Rochester are calling a discovery they made in a mysterious region of the chromosome known as the centromere a potential game-changer in the field of chromosome biology.

“We’re really excited about this work,” says Amanda Larracuente, the Nathaniel and Helen Wisch Professor of Biology, whose lab oversaw the research that led to the findings, which appear in PLOS Biology.

The discovery involves an intricate and seemingly carefully choreographed genetic tug-of-war between elements in the centromere, which is responsible for proper cell division. Instead of storing genes, centromeres anchor proteins that move chromosomes around the cell as it splits. If a centromere fails to function, cells may divide with too few or too many chromosomes.

These critical structures are rich in what biologists call “selfish” genetic material—transposable elements that move within the genome, and thousands of repeated segments of DNA known as “satellite DNAs”—that often compete during cell division to ensure their own transmission.

For centromeres to function effectively, though, these competing elements must also cooperate.

“In biology, we’re used to thinking about things that have essential roles as being highly conserved,” Larracuente says. “So, it’s fascinating that they are the opposite of highly conserved. They are rapidly evolving.”

‘Dramatic’ centromere reorganization

To learn more about the interplay between these elements, researchers studied closely related species of fruit flies, or Drosophila, and found that centromeres frequently switched between types of transposable elements and satellite DNA in short spans of evolutionary time.

“Repetitive sequences are known to evolve rapidly in general,” Larracuente says. “But what we found was a dramatic centromere reorganization over two short evolutionary timescales.

“We didn’t just see different variants of the same sequence in different species, we found categorical shifts in the types of elements.”

The researchers used chromatin profiling and high-resolution imaging on stretched chromatin fibers to observe these shifts in detail.

“Regardless of the evolutionary forces driving this turnover,” reads the study, “the rapid reorganization of centromeric sequences over short evolutionary timescales highlights their potential as hotspots for evolutionary innovation.”

The lab is interested in understanding the roles these DNA sequences play in centromere function and stability in future work. Larracuente says the discovery and subsequent study of centromere dynamics could have potential applications in the long-term for how we treat diseases and disorders characterized by genome instability, such as cancer, and other aging-related diseases.

“Those can be related to centromere defects,” Larracuente says. “Learning how DNA sequences contribute to centromere organization and function could help us understand abnormal centromere behavior.”