Mysterious protein changes the shape of human DNA
We can be shapechangers!
The differences between human and mosquito DNA aren’t limited to the arrangement of letters in the genetic code. If you were to slice open a human cell and a mosquito cell and peer into the nucleus of each, you’d see that their chromosomes are folded with a dramatically different type of genetic origami. Now researchers have figured out how to fold one type of DNA to take the shape of the other.
“In the human nucleus the chromosomes are bunched into tidy packages,” said Claire Hoencamp, a doctoral candidate at the University of Amsterdam. “But in the mosquito nucleus the chromosomes are folded in the middle.”
Hoencamp was studying condensin II, a protein involved in cell division. In one experiment she destroyed this protein in a human cell to observe its effect on the cell cycle. As if by elaborate choreography, the resulting cell’s chromosomes would refold, but not like the DNA in a human nucleus.
Meanwhile, Olga Dudchenko, a postdoctoral researcher at the Center for Genome Architecture in Texas, was classifying genomes based on the 3D structures their chromosomes form. As co-director of a multi-institutional project called DNA Zoo, she was seeing some distinct patterns. “We can classify things into two basic architectures,” she said, referencing the tightly coiled and compartmentalised nature of the human genome versus the looser arrangement of the mosquito genome. No matter how many species she examined, chromosomes took on variations of two basic shapes. Her research suggested that some lineages would use one shape and evolve into the second and, in many cases, evolve back. However, she didn’t know what force, if any, was driving these changes.
When presenting their research, the two teams realised they were approaching the same problem from different angles. Hoencamp had found a protein that folds chromosomes, and Dudchenko had spotted Hoencamp’s experiment happening naturally across evolutionary timescales.
Due to COVID-19, the collaborators turned to computer simulations to better understand condensin II’s role in nuclear organisation. With help from a laboratory at Rice University in Houston, they simulated the effects of condensin II on the millions to billions of letters in a genome, confirming what Hoencamp had found in her previous experiments.
Future research will aim to determine what evolutionary advantage, if any, one nucleus structure might have over the other. When the researchers examined gene expression, they found the folding structure of the chromosomes only mildly affected gene expression, or how much of each protein was made by different genes.
Given how little folding affected gene expression, it’s not clear why a species would fold its DNA one way or the other. However, because both folding methods are found across the evolutionary tree, the subtle effects of each might have big implications.
CAMERON DUKE