Green’s computer programs are famous for their elegance and precision, but his office is a mess: stacks of books, articles, and monographs cover every flat surface. He stands partly hidden behind a wall of paper, wearing clothes appropriate for either a mathematician or a Seattle rock star—sandals, jeans, flannel shirt. His wire-rim glasses and square gray beard convey the impression of someone so unfashionable that he has become fashionable again.

Lately, his curiosity has been drawn to how and why DNA mutates. “The changes that occur in functional DNA are the raw material for evolution,” Green says. “Those changes create variation in organisms, and then selection goes to work on that variation,” with organisms that have advantageous mutations thriving and reproducing their DNA while deleterious mutations hit an evolutionary dead end. “That’s Darwin’s paradigm,” he says, “and that’s what drives evolution.”

But Green’s approach to drawing out the function of DNA is counterintuitive. He has been looking at the 95 percent or so of our genome that doesn’t seem to be doing anything. “We think that part of the genome is actually quite interesting,” he says, “because by studying it, you can find out about mutation. Selection is not acting on that part of the sequence, so it provides a more or less faithful record of the mutation process.”

Green and graduate student Dick Hwang have analyzed, in 19 different mammals, the nonfunctional DNA sequences in a region containing the gene that is mutated in cystic fibrosis. Using a detailed computational model, they found that some kinds of mutations occur at constant rates, like the ticking of a clock, which makes them useful for dating evolutionary events. Other kinds of mutations occur at varying rates depending on the generation times of the organism. This information in turn makes it much easier to identify parts of the genome that exhibit different patterns of change over time, indicating that the DNA in those regions is subject to selection and therefore playing a functional role. The idea, says Green, is to separate the noise of meaningless changes in DNA so that the signals of consequential changes emerge clearly from the background.

This elegant approach to a fundamental question typifies Green's work, say his colleagues at the University of Washington. "He really struggles to understand what the problem is," says geneticist Maynard Olson, whose office is a few corridors away from Green's. "And he really wants his work to address the problem—not just be related to it."

These qualities make Green especially sought after as a reviewer. Once, he wrote such a careful and detailed review of a paper submitted to the journal Genome Research that the editors convinced him to let them publish the review as an accompaniment to the original paper. When asked to review the paper written by the Human Genome Project announcing the completion of the human sequence, he wrote 23 single-spaced pages over the course of 7 days. “It was the deepest, most thoughtful review we received and made the paper much better,” says Eric Lander, director of the Broad Institute in Cambridge, Massachusetts, and lead author on the paper. “When it comes time to publish the collected papers of Phil Green, the collected peer reviews should be published, too.”

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