Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Missing steps of jumping-gene replication discovered

01.02.2006


Findings illuminate how ’junk’ DNA accumulates in the human genome



In experiments with transgenic mice, University of Pennsylvania School of Medicine researchers discovered the remaining steps in the complicated process of how the largest class of jumping genes replicates and inserts themselves within the human genome. Haig H. Kazazian, Jr. MD, Chair of the Department of Genetics, and colleagues at Penn published their findings in the February issue of Genome Research. This knowledge may shed light on the origins of "junk" DNA, parts of the genome for which no function has yet been discovered.

Jumping genes–also called mobile DNA or transposons–are sequences of DNA that can move or jump to different areas of the genome within the same cell. They are a rare cause of several genetic diseases, such as hemophilia and Duchenne muscular dystrophy.


Retrotransposons are one class of jumping genes, with the L1 family being the most abundant in the human genome. Retrotransposons move by having their DNA sequence transcribed or copied to RNA, and then instead of the genetic code being translated directly into a protein sequence, the RNA is copied back to DNA by the retrotransposon’s own enzyme called reverse transcriptase. This new DNA is then inserted back into the genome. This process of copying is similar to that of retroviruses, such as HIV, leading scientists to speculate about a viral origin for retrotransposons.

"L1 retrotransposons, which are the only active mobile DNA elements in humans, have accounted for about 30 percent of the human genome by their own insertions and by driving the insertion of other kinds of elements," says Kazazian. "In fact, humans have over 500,000 L1 retrotransposons within an individual genome."

In order to learn about the effects of L1 retrotransposon insertions into the human genome, the researchers made a transgenic mouse in which human L1 retrotransposons could replicate. They injected several copies of a human L1 retrotransposon to create the transgenic mouse. In subsequent generations, the retrotransposons moved within the offsprings’ genomes and each new insertion could be detected by the investigators. The researchers characterized 51 new jumps of L1, finding that insertions landed in random genomic regions. Several L1 insertions included small pieces of extra DNA.

While tracing the origin of this extra DNA, Daria Babushok, an MD/PhD student in the Kazazian lab, came up with the missing steps in the mechanism of retrotransposon replication. "It was known previously that the enzyme endonuclease cleaves one of the strands of cellular DNA and then the retrotransposon inserts by binding to that cleaved DNA strand and copying itself onto that strand," she says. "It sneaks in there."

How the retrotransposon finally integrated and pasted itself back together was unknown, until this paper. "What we saw in our insertions hinted at the possibility that reverse transcriptase actually jumps onto the second DNA strand and continues the synthesis," she explains. "We think that this is how the second part of the element integrates into the genome. If this mechanism proves to be correct, it will bring us much closer to knowing how more than half a million retrotransposons have accumulated in the human genome."

Eventually, continuous jumping by retrotransposons expands the size of the human genome and may cause shuffling of genome content. For example, when retrotransposons jump, they may take portions of nearby gene sequences with them, inserting these where they land, and thereby allowing for the creation of new genes. Even otherwise unremarkable insertions of L1 may cause significant effects on nearby genes, such as lowering their expression.

Now, by knowing the final steps in retrotransposon replication and being able to follow and map new insertions in animals, the researchers will be able to more fully understand how L1 retrotransposons are able to invade the human genome.

"We were able to obtain a snapshot of a large number of new L1 jumps in a situation closely mimicking what occurs every day in the human genome," says Babushok. "Importantly, occasional small additions of extra DNA sequences at the ends of new L1 insertions gave us tantalizing leads to the L1 retrotransposon replication mechanism. We are very excited to follow this thread to confirm our proposed mechanism and to come closer to a complete understanding of the interaction between L1 retrotransposons and our genomes."

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu/news/

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>