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Single-celled organisms have stiffer DNA than multicellular lifeforms like humans and rice. Theoretical physicists managed to simulate the folding in full genomes for the first time to reach this conclusion. Publication in Biophysical Journal on February 7.
Our DNA stores information using four base letters, which encode for the proteins that arrange all processes in our body. With a length of about two meters each, DNA molecules need to cozily curl up to fit inside our tiny cells. Local variations in stiffness allow for less or more wrapping, affecting the readability per set of letters. These mechanical cues in genes provide a second layer of information, as Leiden physicist Helmut Schiessel theoretically demonstrated earlier.
Now in a follow-up research, Schiessel and his colleagues have improved their computer model, allowing them to calculate folding in the full genome of fifty different species. This led to the discovery of a new general rule in biophysics: unicellular species—like yeast—are characterized by stiff stretches in their DNA sequence at the beginning of genes, while multicellular lifeforms—like humans, mice or zebrafish—have soft stretches. ‘Unicellular species need access to all their genes in the one cell they have,’ Schiessel explains. ‘Therefore it needs stiff DNA so it is easily read out. Humans have many different types of cells and we find that this is reflected in soft DNA.’
To make their discovery, the researchers averaged over many simulated gene sequences and looked at the stiffness right at the beginning of a new gene. Comparison with real-life experiments shows that the model works. Schiessel: ‘Our simulation is much faster than experiments, so we were able to analyze for the first time the full genome of several lifeforms. You would think from our finding: “the softer the DNA, the more complex the lifeform,” but funny enough we found rice to have the softest DNA of all the species we analyzed.’
‘Genomes of Multicellular Organisms Have Evolved to Attract Nucleosomes to Promoter Regions’, M.Tompitak, C. Vaillant and H. Schiessel, Biophysical Journal
The researchers modeled DNA wrapping in 50 different lifeforms. The x-axis spatially represents 2000 base pair long stretches of DNA. The nucleosome occupancy (y-axis) is a measure for the likelihood of the DNA to be wrapped. Large values indicate soft DNA. Rice appears to have softer DNA than for example humans.
Delft, Toeno van der Sar lab
Leiden, Milan Allan lab
Leiden, Stefan Semrau lab
Leiden, Milan Allan lab
Delft, QN/Sonia Conesa-Boj lab
Delft, QN/Sander Otte lab