Tuesday, December 04, 2007


The New Yorker has an amazing piece on endogenous retroviruses -- retroviruses that succeeded in injecting their RNA into our DNA via germline cells such as sperm or eggs. These fragments of genetic code constitute 8 percent of our entire genome, whereas protein-producing genes are only 2 percent.

Biologists can now reconstruct these long extinct viruses from the fragments, even correcting for mutations or copy errors by comparing different versions and using statistical models to guess at the original code.

...to alter our genetic structure. That would require an organism to insinuate itself into the critical cells we need in order to reproduce: our germ cells. Only retroviruses, which reverse the usual flow of genetic code from DNA to RNA, are capable of that. A retrovirus stores its genetic information in a single-stranded molecule of RNA, instead of the more common double-stranded DNA. When it infects a cell, the virus deploys a special enzyme, called reverse transcriptase, that enables it to copy itself and then paste its own genes into the new cell’s DNA. It then becomes part of that cell forever; when the cell divides, the virus goes with it. Scientists have long suspected that if a retrovirus happens to infect a human sperm cell or egg, which is rare, and if that embryo survives—which is rarer still—the retrovirus could take its place in the blueprint of our species, passed from mother to child, and from one generation to the next, much like a gene for eye color or asthma.

When the sequence of the human genome was fully mapped, in 2003, researchers also discovered something they had not anticipated: our bodies are littered with the shards of such retroviruses, fragments of the chemical code from which all genetic material is made. It takes less than two per cent of our genome to create all the proteins necessary for us to live. Eight per cent, however, is composed of broken and disabled retroviruses, which, millions of years ago, managed to embed themselves in the DNA of our ancestors. They are called endogenous retroviruses, because once they infect the DNA of a species they become part of that species. One by one, though, after molecular battles that raged for thousands of generations, they have been defeated by evolution. Like dinosaur bones, these viral fragments are fossils. Instead of having been buried in sand, they reside within each of us, carrying a record that goes back millions of years. Because they no longer seem to serve a purpose or cause harm, these remnants have often been referred to as “junk DNA.” Many still manage to generate proteins, but scientists have never found one that functions properly in humans or that could make us sick.

Then, last year, Thierry Heidmann brought one back to life. ...

...The Nobel Prize-winning biologist Joshua Lederberg once wrote that the “single biggest threat to man’s continued dominance on this planet is the virus.” Harmit Malik, an evolutionary geneticist at the Fred Hutchinson Cancer Research Center, acknowledges the threat, yet he is confident that viruses may also provide one of our greatest scientific opportunities. Exploring that fundamental paradox—that our most talented parasites may also make us stronger—has become Malik’s passion. “We have been in an evolutionary arms race with viruses for at least one hundred million years,’’ he told me recently, when I visited his laboratory. “There is genetic conflict everywhere. You see it in processes that you would never suspect; in cell division, for instance, and in the production of proteins involved in the very essence of maintaining life.

“One party is winning and the other losing all the time,” Malik went on. “That’s evolution. It’s the world’s definitive game of cat and mouse. Viruses evolve, the host adapts, proteins change, viruses evade them. It never ends.” The AIDS virus, for example, has one gene, called “vif,” that does nothing but block a protein whose sole job is to stop the virus from making copies of itself. It simply takes that protein into the cellular equivalent of a trash can; if not for that gene, H.I.V. might have been a trivial disease. “To even think about the many million-year processes that caused that sort of evolution,” Malik said, shaking his head in wonder. “It’s dazzling.” Malik grew up in Bombay and studied chemical engineering at the Indian Institute of Technology there, one of the most prestigious technical institutions in a country obsessed with producing engineers. He gave no real thought to biology, but he was wholly uninspired by his other studies. “It was fair to say I had little interest in chemical engineering, and I happened to tell that to my faculty adviser,’’ he recalled. “He asked me what I liked. Well, I was reading Richard Dawkins at the time, his book ‘The Selfish Gene’ ”—which asserts that a gene will operate in its own interest even if that means destroying an organism that it inhabits or helped create. The concept fascinated Malik. “I was thinking of becoming a philosopher,’’ he said. “I thought I would study selfishness.” ...

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