Retrotransposons Are Necessary for Cell Targeting and Circulatory DNA Incorporation

Organisms benefit from gene transfer between cells, both physiologically and pathologically. Horizontal gene transfer (HGT) creates more significant alterations in the genome evolution of prokaryotes than the branching trajectory. The acquisition of novel characteristics by HGT can offer prokaryotes survival and evolutionary advantages in the face of environmental challenges.

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Life Cycle of a Retrotransposon

Life Cycle of a Retrotransposon. Credit: Marius Walter

In some eukaryotes, such as insects and plants, the exchange of genetic material via transposons is a common form of HGT.

With transposon-mediated genetic exchange in rice and millet plants, the extensive evidence of transposon-mediated HGT in plants, particularly parasitic plants, has been discovered.

Collecting genetic material from the host plant permits parasitic plants to evolve more quickly to adapt to new and changing surroundings. The precise timing of transposon-mediated HGT marks the branch point in the evolution of different variants of the invading plants on numerous occasions.

In contrast to the preceding cases, the evidence for HGT and any probable mechanism involved in humans is less well established.

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Current research show retrotransposons are necessary for cell targeting. The retrotransposons can also aid circulatory DNA (ctDNA) incorporation into host DNA. The researchers discovered that tissue-specific retrotransposons govern the process by which ctDNA targets and transmits genetic material to cells that are similar to their cell of origin.

The novel finding can be beneficial for gene transfer

Few studies have shown the migration of non-gene-coding areas across human cells under physiological settings. Early evidence in immunology suggests that the exchange of cell-free DNA from a T cell can cause B cells to produce antibodies. Evidence is considerably more scarce in pathological situations such as cancer. The revelation that tumor-derived cell-free DNA can carry genetic changes essential to carcinogenesis prompted researchers to consider the notion that circulating tumor DNA (ctDNA) serves as a channel for genetic exchange between tumor cells throughout the last decade.

Results from previous studies show gene transfers can influence tumor phenotype. These happen through the transfer of oncogenic genes or changes in the tumor microenvironment.

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However, until now, definitive proof of ctDNA-mediated HGT and the mechanism behind HGT has been missing.

Horizontal transposable element transmission is vital in the evolution of prokaryotes and some eukaryotes. However, the role of HGT in humans is not well understood. The scientists in this new study observed that bare ctDNA could transport genes across cancer cells. They identified a previously unknown property of ctDNA: its predilection towards cells identical to those from which it originated.

Furthermore, the investigations with retrotransposon deletion mutants revealed that these components include the address that defines the transport of ctDNA to a specific target cell.

Clinical significance

The transfer of genetic information, with blood transfusion, between people is a distinct possibility of the present research findings. The study also shows the ability of ctDNA in targeted tumor cells, adding a powerful new method to treat cancer and other diseases.

Conclusion

The research is a novel finding in gene science. It shows the discovery of retrotransposons at ctDNA insertion sites. It also shows the reduction of ctDNA insertions by retrotransposition inhibitors. Molecules can reach the target cell through retrotransposons artificially generated. Thus, retrotransposons play a vital role in HGT mediation in cancer.

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References

Retrotransposons facilitate the tissue-specific horizontal transfer of circulating tumor DNA between human cells | bioRxiv

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