Jumping genes discovery 'challenges current assumptions'

Jun 12, 2009

Jumping genes do most of their jumping, not during the development of sperm and egg cells, but during the development of the embryo itself. The research, published this month in Genes and Development, "challenges standard assumptions on the timing of when mobile DNA, so-called jumping genes, insert into the human genome," says senior author Haig H. Kazazian Jr., MD, Seymour Gray Professor of Molecular Medicine in Genetics at the University of Pennsylvania School of Medicine.

Jumping genes - also called transposons - are sequences of DNA that can move or jump to different areas of the genome within the same cell. Jumping gene insertions do cause disease; however, it's not known how frequently diseases due to insertions can be inherited in the next generation. They are a rare cause of several , such as hemophilia and Duchenne muscular dystrophy. In addition, transposon insertion into the genome could play a role in the development of cancer.

The current work alters thinking in the field of jumping genes, challenging standard assumptions that mobile DNA inserts only in eggs and sperm during their respective early development. In this study, the researchers found that insertions took place during embryogenesis after fertilization, at a time when nearly all of the changes can't be inherited. The researchers now purport, based on the study's findings, that many of those insertions occur in the early embryo, perhaps in the 4- or 8-cell stage.

The study looked at retrotransposons, one class of , with the L1 family the most abundant type of retrotransposon 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. The process of copying is similar to that of retroviruses, such as HIV, leading scientists to speculate that retroviruses were derived from retrotransposons.

The L1 family of retrotransposons comprises about 17 percent of the human genome. Eventually, continuous jumping by retrotransposons expands the size of the 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.

Insertions can come from an L1 retrotransposon that is in the genome of the embryo or it can arise from an L1 that was in a parent and is not in the embryo. In the latter case, the L1 RNA from that parent is carried over through fertilization and inserts in the embryo. Insertions in the latter case are much less frequent than when the L1 itself is present in the genome of the embryo.

Despite L1 abundance in the genomes of mammals, relatively little is understood about L1 retrotransposition outside of the test tube. Using transgenic mice and rats containing human or mouse L1 elements, the team demonstrated abundant L1 RNA in both egg and sperm cells and embryos. However, the integration events usually occur during the development of the embryo rather than in egg or sperm cells and are not heritable.

They also demonstrated that L1 RNA transcribed in egg or sperm cells can be carried over through fertilization and integrate during embryogenesis, an interesting example of heritability of RNA independent of its encoding , creating somatic mosaicism during mammalian development. Soma are all cells other than egg or . A cell mosaic is an insertion that occurs after fertilization in which some cells have the insertion and others don't within the same tissue type. The mosaicism suggests a role for L1 in carcinogenesis and other diseases; for example cancerous growth may be initiated if insertions happen near an oncogene.

Source: University of Pennsylvania School of Medicine (news : web)

Explore further: First genetic link discovered to difficult-to-diagnose breast cancer sub-type

add to favorites email to friend print save as pdf

Related Stories

Mapping a clan of mobile selfish genes

Oct 22, 2008

Much of human DNA is the genetic equivalent of e-mail spam: short repeated sequences that have no obvious function other than making more of themselves.

Maelstrom quashes jumping genes

Aug 11, 2008

Scientists have known for decades that certain genes (called transposons) can jump around the genome in an individual cell. This activity can be dangerous, however, especially when it arises in cells that produce eggs and ...

A gene for metastasis

Aug 28, 2007

Colorectal cancer is one of the most prevalent cancers in the Western world. The tumor starts off as a polyp but then turns into an invasive and violent cancer, which often spreads to the liver. In an article recently published ...

Silencing of jumping genes in pollen

Feb 05, 2009

Scientists at the Instituto Gulbenkian de Ciência (IGC), in Portugal, are to date the only research group in the world capable of isolating the sperm cells in the pollen grain of the model plant Arabidopsis thaliana. This ...

Recommended for you

Refining the language for chromosomes

Apr 17, 2014

When talking about genetic abnormalities at the DNA level that occur when chromosomes swap, delete or add parts, there is an evolving communication gap both in the science and medical worlds, leading to inconsistencies in ...

Down's chromosome cause genome-wide disruption

Apr 16, 2014

The extra copy of Chromosome 21 that causes Down's syndrome throws a spanner into the workings of all the other chromosomes as well, said a study published Wednesday that surprised its authors.

User comments : 0

More news stories

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Study says we're over the hill at 24

(Medical Xpress)—It's a hard pill to swallow, but if you're over 24 years of age you've already reached your peak in terms of your cognitive motor performance, according to a new Simon Fraser University study.

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.