In new research published in the journal Nature, a team of Duke University scientists revealed a surprising finding about retrotransposons—genetic sequences that were previously thought to be parasitic. Far from being useless by-products of imperfect gene replication, the researchers discovered that retrotransposons actually 'hijack' the host cell's DNA repair mechanisms, molding themselves into ring-like structures and generating corresponding double strands.
Retrotransposons are DNA segments around 7,000 base pairs long that can clone themselves and integrate into various sections of a plant or animal's genome. By altering DNA and impacting gene regulation, they significantly contribute to genetic variation and evolution. In fact, retrotransposons make up approximately 40% of the human genome and over 75% of the maize genome. Evidence also suggests their involvement in cancer progression and the formation of circular DNA in HIV, the virus that causes AIDS.
The process of retrotransposon copying has long been a topic of uncertainty. Textbooks traditionally suggest that their circular formations result from combining the ends of linear DNA, marking a dead-end or failed replication attempt.
However, the Duke University team's research tells a different story. In earlier work with fruit fly eggs, they found that inherited retrotransposons use supporting 'nurse cells' as factories to produce copies of themselves, which are then distributed throughout the fly egg's genome. Building on this, the latest study showed that most newly added retrotransposons adopt a circular form instead of integrating into the host genome.
The researchers further pinpointed how these circular formations occur. They discovered that the retrotransposons use a lesser-known DNA repair mechanism called alternative end-joining DNA repair (alt-EJ) to join the ends of their single-stranded DNA. The cell's DNA synthase then helps create a matching double-strand.
This revelation subverts the long-held belief that retrotransposon formations are merely accidental. It turns out they deliberately commandeer a part of the cell's machinery to reproduce, similar to how viruses operate.
The research has implications beyond just revising textbook knowledge. Zhao Zhang (ZZ), an assistant professor of pharmacology and cancer biology at Duke University and a Science & Technology scholar, said his lab is now exploring whether circular DNA can insert new genome sequences and trigger immune responses.
Zhang argues for a shift in the scientific community's perspective: “People think circular DNA is just a minor event, but our study is bringing circular DNA into the center stage,” he said. “People should pay more attention to circular DNA.”
Retrotransposons are DNA segments around 7,000 base pairs long that can clone themselves and integrate into various sections of a plant or animal's genome. By altering DNA and impacting gene regulation, they significantly contribute to genetic variation and evolution. In fact, retrotransposons make up approximately 40% of the human genome and over 75% of the maize genome. Evidence also suggests their involvement in cancer progression and the formation of circular DNA in HIV, the virus that causes AIDS.
The process of retrotransposon copying has long been a topic of uncertainty. Textbooks traditionally suggest that their circular formations result from combining the ends of linear DNA, marking a dead-end or failed replication attempt.
However, the Duke University team's research tells a different story. In earlier work with fruit fly eggs, they found that inherited retrotransposons use supporting 'nurse cells' as factories to produce copies of themselves, which are then distributed throughout the fly egg's genome. Building on this, the latest study showed that most newly added retrotransposons adopt a circular form instead of integrating into the host genome.
The researchers further pinpointed how these circular formations occur. They discovered that the retrotransposons use a lesser-known DNA repair mechanism called alternative end-joining DNA repair (alt-EJ) to join the ends of their single-stranded DNA. The cell's DNA synthase then helps create a matching double-strand.
This revelation subverts the long-held belief that retrotransposon formations are merely accidental. It turns out they deliberately commandeer a part of the cell's machinery to reproduce, similar to how viruses operate.
The research has implications beyond just revising textbook knowledge. Zhao Zhang (ZZ), an assistant professor of pharmacology and cancer biology at Duke University and a Science & Technology scholar, said his lab is now exploring whether circular DNA can insert new genome sequences and trigger immune responses.
Zhang argues for a shift in the scientific community's perspective: “People think circular DNA is just a minor event, but our study is bringing circular DNA into the center stage,” he said. “People should pay more attention to circular DNA.”