Contrary to what you may have heard, your genome is not a highly sophisticated, finely tuned data storage and processing device. It's a post-apocalyptic wasteland. Your 25,000 genes reside in a genetic landscape littered with the rubble of ancient and ongoing battles with hordes of viruses, clone armies of genetic parasites, and zombie genes that should be dead but aren't. Our messy genomic landscape is a dynamic, miniature ecosystem, and scientists are learning how its inhabitants play a big role in human health and disease.
Most large genomes carry an exotic bestiary of genetic hangers-on that exploit both the host genome and each other to do what all life does: survive and reproduce. The major players in our genomic ecosystem are DNA parasites called transposable elements, named for their ability to move around the genome and make copies of themselves. Transposable elements, which make up at least half our genome, are "selfish" genetic elements that exist because they have a strategy to get passed on to the next generation without necessarily contributing any useful function to the organism. Other denizens of our DNA include Human Endogenous Retroviruses (HERVS, eight percent of our genome), viruses that took up permanent residence in the egg or sperm cell of one of our distant ancestors, and zombie “pseudogenes,” functional genes that were killed by some genetic mishap but still have an influence on their surrounding genes.
Our messy genomic landscape is a dynamic, miniature ecosystem, and scientists are learning how its inhabitants play a big role in human health and disease.
To counter the spread of transposable elements or the influence of zombie genes, cells have several defense mechanisms that for the most part do an admirable job, but they're not perfect. Humans have accumulated more than one million copies of the Alu transposable element, and a recent paper reports that one species of HERV expanded dramatically some time after the split between our lineage and the Neanderthals, during the last few hundred thousand years. Occasionally, for poorly understood reasons, cellular countermeasures fail, as in the case of the Australian Lungfish, whose genome is eight times as large as ours and has been completely overrun with transposable elements.
As scientists have come to better understand the ecosystem-in-miniature of our genome, two major questions have emerged. First, how much of our DNA does something useful? Last September, the ENCODE consortium, charged with making an inventory of all functional elements in the human genome, stirred up a contentious debate with their widely reported claim that the human genome consists mostly of functional DNA, contrary to the prevailing scientific consensus. But genomic parasites whose only function is self-preservation are clearly not inert pieces of DNA, and thus it's extremely difficult to distinguish them from DNA that plays a useful role in our biology. In fact, as we characterize our genome in ever finer detail, the distinction between functional and non-functional DNA is breaking down. Researchers are finding that transposable elements have played constructive roles in the evolution of our genetic regulatory networks by creating new links between genes.
The second major question is, what role do these active genomic elements play in human disease? The authors of a recent literature review note that scientists are discovering that transposable elements are a much larger source of genetic variability than we thought. New mutations caused by these elements range from one-in-20 to one-in-200 births, and researchers have documented clear cases of transposable element mutations causing diseases like hemophilia, cystic fibrosis, and muscular dystrophy. There is also growing evidence that transposable elements are especially active in cancer. The abnormal state of a tumor cell seems to weaken the genome's defense mechanisms, giving the hordes of genomic parasites a fresh opportunity to mobilize. Infection with HIV can have similar effects, and it's an open question whether certain drugs that alter the state of our genome can activate transposable elements.
The idea that your genome is an ecosystem populated with species that pursue their own self-interest may make you wonder: Who am I, really? Unlike the parasites that you pick up when you drink the water in a place where you shouldn't, transposable elements and endogenous viruses aren't really foreign invaders; they are your DNA, and they have been part of our genetic identity for longer than we have existed as a species. They are among the raw materials from which our genes have been assembled, and a clear demonstration that our genetic core is a product of evolution. Like our social identities, our genetic identities are the result of competition, conflict, cooperation, and accommodation. Learning how our genome's ecosystem works is a key part of our efforts to understand the relationship between our DNA and our health.