Genome Research paper reports 10,000 elements that can move around.
Researchers have found that Alu retrotransposons is by far the most abundant class of jumping genes and poses the greatest transposon-mediated threat to our genomes. The discovered that 10,000 Alu elements are still capable of jumping around, with 37,000 having at least a low level of activity. The youngest ones were all capable of moving around, and the oldest ones were all inactive.
Named after the recognition site they usually include for the enzyme Alu I (AGCT), Alu retrotransposons hijack part of the cell during the copying process by mimicking the signal recognition particle that guides protein production. Alus are known to take up 10% of our genome with about one million copies.
“I think of them as molecular machines that can copy themselves and move around the genome,” says Scott Devine, Ph.D., assistant professor of biochemistry at Emory University School of Medicine. “These elements pose a major threat to our genetic information, because they can damage genes when they jump into them, leading to altered traits or diseases such as cancers.”
The research team wanted to find out why some Alu elements are mobile, while others are not. As mutations gradually blur the features of older Alu elements, some become unable to make copies of themselves.
To identify the Alu retrotransposons divided them into 89 families and put a representative from each on a small circle of DNA next to a gene that allows human cells to resist a poisonous drug. They then introduced the DNA circles into cells in culture dishes. If the Alu element could jump, carrying the drug-resistance gene onto the cells’ chromosomes, the cells survived the drug.
Depending on the type of cell, if an Alu element is located near genes that have been shut off, the Alu element is less likely to get transcribed. That means the number of Alu elements that do move around is probably slightly lower. The team has constructed a database of Alu elements to compile additional information about each family.
Devine says an enzyme that is part of the normal machinery of the cell transcribes Alu elements, but they actually depend on another type of repetitive element, called L1, to make the enzyme that can reverse-transcribe them.
Scientists think Alu elements hijack part of the cell during the copying process. In the cell, Alu RNA is thought to resemble another type of RNA that guides protein production. The team’s tests indicate that Alu elements that can best mimic that RNA, called the signal recognition particle, are more likely to be active.
The results are published online and are scheduled to appear in the December issue of the journal Genome Research. Laboratories at Emory, the University of Michigan, and the Max Planck Institute for Developmental Biology contributed to the study.