Mysterious twisted DNA structures discovered in human blood

Scientists from the University of Cologne have discovered unusual four-stranded DNA structures in human blood plasma that differ dramatically from the familiar double helix. These are so-called G-quadruplexes — compact structures formed from guanine-rich regions of genetic material. The results of the study have been published as a preprint on bioRxiv.

In conventional understanding, DNA is a double helix consisting of two linked strands. However, individual fragments of genetic material can fold in entirely different ways. In a G-quadruplex, four guanine bases come together to form a flat structure, and several such "squares" stack on top of one another, creating a stable construction.

The researchers focused their attention on ultrashort cell-free DNA — tiny fragments of genetic material that enter the bloodstream during natural cell death. These molecules can be as short as approximately 50 "genetic letters."

To determine whether G-quadruplexes are preserved directly in plasma, the scientists employed a gentle extraction method that was not expected to disrupt the material's spatial organization. The samples were then tested using two independent approaches: an antibody that recognizes G-quadruplexes and a special fluorescent molecule. Both methods yielded positive results.

A series of additional experiments confirmed that the detectors were interacting specifically with folded structures rather than randomly binding to genetic material. According to the authors, these are the first direct biochemical evidence of G-quadruplexes being present in nucleic acids isolated directly from human plasma.

However, the scientists have not yet established whether the discovered structures are specifically DNA or RNA: both molecules are capable of forming G-quadruplexes. Another question also remains open — whether they fold inside cells or only after entering the bloodstream.

The researchers emphasize that G-quadruplexes are found in regions of the genome associated with gene activity regulation, and changes in them have been observed in certain types of cancer. Nevertheless, the new study does not prove that the discovered structures can be used for tumor diagnosis.