Illustration by Jacob Magraw
In the campus gardens of the Cold Spring Harbor Laboratory, the center for genetics research on Long Island, stands a 15-foot molecule. Made by the architect Charles Jencks, it is an aluminum sculpture of DNA whose structure James Watson, the laboratory's president, deduced with Francis Crick in 1953. Its twinned spiral strands have now come to represent nothing less than life itself: Within these helices, so we are told, lie all the instructions for making an organism, passed from one generation to the next by copying the DNA blueprint.
But over the past year or so, it has begun to look increasingly as though biologists may need to reconsider the role of their favorite molecule. For nearly 50 years, the central dogma of biology has been that genetic information is contained within DNA and is passed by rote transcription through RNA to make proteins. Tiny changes in the information content of the underlying DNA are what then drive evolution. But this information may not be the sole determinant of biological identity. Indeed, it's becoming clear that we do not even know what 'genetic information' means any more—certainly it's not a simple, linear sequence of biochemical 'characters' that define a gene. Even evolution might not be driven solely by the appearance of random mutations in DNA that are inherited by subsequent generations, essentially as Darwin supposed. The central dogma is being eroded, and it now appears as if DNA's cousin, the humble intermediary RNA, plays at least an equal role in genetics and the evolution of the species.
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Who says so? Consider the work of Minoo Rassoulzadegan at the French National Institute for Health and Medical Research's laboratory in Nice. Last year she showed that mice could inherit white patches on their tails—normally the result of a mutation in a gene called Kit—even if they lacked the mutant gene for this trait. The white patches appeared because RNA molecules, which passed from parent to offspring after accumulating in sperm cells, overrode the demands of DNA.
Or take the work of David Haussler and his colleagues at the University of California, Santa Cruz. They have shown that a gene called HAR1F, which is probably responsible for some key differences between human and chimpanzee brains, doesn't even make a protein, only an RNA molecule. In other words, the human brain may have evolved through the guidance of RNA.
These and a host of other recent findings are rewriting the textbooks of molecular biology. They are beginning to show not only that RNA is more fundamental to genetics than once believed, but also that it can directly affect evolution and elucidate the differences between species. The result is a story that looks a lot messier, but potentially a lot more interesting, than anyone ever guessed.
The old genetic picture seemed so beautifully simple—indeed, probably too beautiful to be true. It began with the identification by the Austro-Hungarian monk Gregor Mendel of discrete, particle-like units that are responsible for the inheritance of traits from one generation to the next. In Mendel's scheme, you either picked up a trait from one parent or you didn't; there was no blending or averaging from both parents. These units became known as genes, and were found to reside on the chromosomes. In 1944 Oswald Avery and his coworkers found that genes are made of DNA. Nine years later Watson and Crick discovered that genes encode information as a sequence of the four different chemical building blocks of DNA, strung along the double strands like beads. From this the central dogma was born.