Arms Race Against Junk DNA Shapes Genome Evolution

Scientists at Georgia Tech have found supporting evidence for a theory they first created in the 1990s, that many of the components that make up our genes are the result of an arms race between the coding and the non-coding parts of the genome.

In the latest issue of BMC - Molecular Biology, these researchers show for the first time that a key regulatory protein, called MOF, plays a central role in the silencing of transposable elements, also known as junk DNA. They hypothesize that this role was MOF's original function - that this and perhaps other regulatory proteins originally evolved as a defense against transposable elements. It was only later that they were co-opted to play an essential role in cellular function.

"Our findings support a growing consensus among molecular evolutionists that transposable elements are not merely 'junk DNA' but have and continue to play an important role in genome evolution" said John McDonald, chair of the School of Biology at the Georgia Institute of Technology and chief research scientist at the Ovarian Cancer Institute.

In this study, McDonald along with Lilya Matyunina and Nathan Bowen first determined that the repression of transposable elements in the fruit fly Drosophila, is due to the manner in which DNA is packaged into chromosomes. They next used genetic techniques to localize the effect to a gene encoding the MOF protein. It turns out that MOF is already well known as a vitally important protein not only in fruit flies but in humans as well. MOF helps ensure that males and females express genes at a uniform level even though they have different numbers of chromosomes -a cellular process known as dosage compensation. The authors propose that MOF originally evolved to silence the activity of transposable elements and was only later co-opted for its current critical role in dosage compensation.

Since McDonald first proposed his theory more than a decade ago, the view that transposable elements are little more than genomic parasites has been gradually replaced by the view that this so-called junk DNA is actually a possible source of new regulatory mutations that help drive evolution and are associated with diseases like cancer.

There are two ways that transposable elements are thought to contribute to evolution. As the elements replicate they end up moving from one location on the genome to another. By inserting themselves in or near existing genes, they can instigate significant changes or mutations in gene expression in the organism and in the traits it exhibits. This can result in new evolutionary changes or in genetic abnormalities that lead to disease.

The second contribution occurs as the host genome tries to repress the mutations by creating proteins that inhibit the ability of transposable elements to replicate. Not about to be outdone, the transposable elements generate new traits that allow them to escape the barriers put forth by the host genome. The result is a genomic conflict of sorts in which new regulatory mechanisms arise because of this struggle. Many of these new mechanisms may end up not having any other function, but others may end up promoting diseases or they might be co-opted by the genome for other cellular functions.

McDonald views the relationship between transposable elements and the host genomes where they reside as a genomic "arms race." Transposable elements are continually trying to invent ways to replicate and move around the genome and host genomes are continually trying to evolve ways to repress this potentially mutagenic activity.

"Just as arms races in human societies generate technologies that can sometimes be co-opted for non-military purposes, so can regulatory mechanisms that were originally evolved to repress transposable elements be subsequently co-opted for essential cellular processes" said McDonald.

McDonald believes that the genomic level war that is being waged between transposable elements and host genomes has been an essential driving force in the evolution biological complexity. "Biologists initially dismissed transposable elements as useless pieces of selfish DNA but the fact is that if it weren't for transposable elements, higher organisms may never have evolved," he said.

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