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The human genome, and most others for that matter, is a massive and complex template containing the written instructions for life. Those instructions, our complement of protein coding genes, make up only about 1.5 percent of the genome and are nestled among billions of base pairs of so-called junk DNA. This is a misnomer, however, as this “junk” contains not only parasitic DNA elements but repetitive sequences and other information crucial for many cellular processes.

A sizable chunk of the “junk” is made up of transposable elements (or transposons) - genetic elements that can move around the genome. Transposons were first identified by maize geneticist Barbara McClintock as a source of unstable mosaic phenotypes that she described in many of her maize lines. Subsequently it was determined that transposons were capable of jumping from one place in the genome to another. Rarely, transposon activity can be advantageous - as a evolutionary force or a source of genetic variation in times of environmental stress. Generally if left unregulated, transposons can wreak havoc in the genome - hopping into genes and causing mutations or even causing massive chromosomal rearrangements. Therefore, elaborate regulatory mechanisms are employed to silence - or inactivate - transposons. These include modifications to chromatin structure, RNA silencing and, as described in an article in the latest issue of Nature, sometimes turning components of the transposons on themselves.

Most of the transposons in the genome are stably silenced and many of them have been “tamed” and do important cellular jobs. For example, in the fission yeast Schizosachharomyces pombe, proteins derived from transposons (CENP-Bs) play a crucial role in cell division. CENP-Bs bind repetitive DNA elements (some of them tranpsosons) in the centromere, which acts as the attachment point for spindle fibers during cell division. Without CENP-Bs, cell division is disrupted. The research published this week, led by Hugh Cam and Shiv Grewal of the U.S. National Cancer Institute, is formed around the hypothesis that CENP-Bs may associate with transposable elements in other regions of the genome as well. Cam and his colleagues found that CENP-Bs bind to Tf2 transposable elements throughout the yeast genome and recruit other proteins to silence the transposons.

The transposon derived CENP-Bs also seem to play a role in preventing new transposable elements from entering the genome. When Cam and his colleagues introduce a related transposable element (Tf1) CENP-Bs blocked its integration into the genome. The authors postulate that a similar system is employed to regulate some transposable elements in other organisms, including humans. Certainly, CENP-B homologs play the same role in centromere function in humans and it is not much of a stretch to hypothesize that they play the same role in control of transposons.

It seems therefore, that proteins derived from a transposable element act to recognize and inactivate related elements. This system is in some ways similar to the mammalian immune system. An invader - the transposon - presents a threat to the cell which responds by detecting the invader and subduing it. CENP-B plays the role of an antibody in this analogy, binding to the transposable elements and preventing their potentially destructive activity. As in the case of biological invaders such as bacteria and viruses, which can change rapidly in attempt to avoid immune system surveillance, transposable elements are prone to mutation. Effectively it is a cellular arms race between parasitic invaders and the defenders of the genome - the twist being that the defenders are derived from the invaders. The circle of life…