Mysterious protein turns human DNA into different shapes


The differences between humans DNA and mosquito DNA is not limited to the arrangement of the letters of the genetic code. If you were to open up a human cell and a mosquito cell and scan the nucleus of each, you would see that their chromosomes are folded up with a radically different type of genetic origami. Now, researchers have figured out how to bend one type of DNA into the shape of another – essentially by twisting human DNA like that of a mosquito.

“In the human nucleus, chromosomes are grouped together in neat bundles,” Claire Hoencamp, a doctoral student in cancer biology at the University of Amsterdam, told Live Science on a video call as she crumpled up a sheet of paper. “But in the mosquito nucleus, the chromosomes are folded up in the middle.” As she spoke, she folded several sheets of paper in half and arranged them like books on a shelf, the pages facing outward.

Related: Life code: Photos of DNA structures

Hoencamp was studying condensin II, a protein involved in cell division. In an experiment, she destroyed this protein in a human cell to observe its effect on the cell cycle. As if by an elaborate choreography, the chromosomes of the resulting cell would fold back. But it didn’t fold like DNA in a human nucleus; instead, he turned into his best impression of the guts of a mosquito core.

Meanwhile, Olga Dudchenko, a postdoctoral researcher at the Center for Genome Architecture at Baylor College of Medicine in Texas, classified genomes based on the 3D structures formed by their chromosomes. As the co-director of a multi-institutional project called DNA Zoo, she saw distinct models.

“Essentially, we can categorize things into two basic architectures,” she said, referring to the tightly coiled and compartmentalized nature of the human genome versus the looser arrangement of the mosquito genome. No matter how many species she has examined, chromosomes took variations of two basic forms.

Disconcertingly, his research suggests that some bloodlines would use one form and evolve into the second, and then, in many cases, evolve backwards. However, she wasn’t sure what force, if any, was causing these changes.

When presenting their research at a conference in Austria, the two teams realized that they were approaching the same problem from different angles. Essentially, Hoencamp had found a protein that folds chromosomes, and Dudchenko had spotted the Hoencamp experience occurring naturally across evolutionary time scales.

After deciding to collaborate, COVID-19 has struck. As access to the laboratory was cut off, employees turned to computer simulations to better understand the role of condensin II in nuclear organization. With help from a laboratory at Rice University in Houston, they simulated the effects of Condensin II on millions or even billions of letters in a genome, confirming what Hoencamp had found in previous experiments.

In a genetic analysis described on May 28 in the journal Science, the researchers looked at 24 species and found that the species with the loosest chromosome arrangement had one thing in common: a broken condensin II gene.

Future research will focus on determining what evolutionary advantage, if any, one core structure might have over the other. When the researchers looked at gene expression, they found that the folding structure of chromosomes only slightly affected gene expression, or how much of each protein was made by different genes. This discovery surprised Hoencamp.

Given how little folding affected gene expression, it is not clear why a species would refold its DNA in any way.

However, since both folding methods are found in the evolutionary tree, the subtle effects of each could have big implications. “Variations in the 3D structure seem to be a matter of fine-tuning,” said Dudchenko, certain functions inside bodies. However, what exactly is changed remains a mystery.

Editor’s Note: Updated June 10, 2021 at 3:20 p.m. ET to note that the Center for Genome Architecture is located at Baylor College of Medicine, not Baylor University as previously reported.

Originally posted on Live Science.


Leave A Reply