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In searching the database of yeast genomes for the regulatory gene, "I noticed an odd pattern," says Hittinger. The gene was present in some, but not all, yeast species. He thought at first that this was a fluke of the data, so he dug further. Hittinger then found one species, Saccharomyces kudriavzevii, that retained the outline not only of the regulatory gene in question but of all seven genes in the galactose pathway. These genes were literally full of holes and other markers, however, indicating that they were nonfunctional: some DNA bases were missing, or the code contained "stop" instructions in the middle of the sequence rather than at the end. Without these genes intact, the yeast lacked the machinery to consume galactose—it had in essence lost its taste for the sugar.
Hittinger took his observations to Carroll, who remembers saying, "Write the paper!" What Hittinger had found was a set of skeletal, or fossil, genes. "I could immediately tell him," says Carroll, "that this was a big story—a remarkable case of seven functionally related genes all in the process of decay."
Hittinger went back to the lab bench to sequence the genes in yeasts where data were incomplete. He and Rokas then pieced together a yeast family tree indicating that the ability to consume galactose was lost at least three separate times in yeast evolution. "Each one of the lineages found itself in a niche where galactose was less important for its survival," says Hittinger. In the case of S. kudriavzevii, which exists in the wild today only in Japan, the researchers note that it also has the unusual ability to consume a complex plant compound called inulin. They speculate that the yeast may have abandoned galactose as it acquired the specialized physiology to exploit a food source that few other organisms have the biochemistry to use. The remnants of the galactose pathway, however, can still be detected as the genes go through the evolutionary process of disappearing.
"It's such a signature of the way natural selection works," says Carroll. "It's use-it-or-lose-it. These genes fell into disuse, and they're being eroded like fossils on a shoreline." 
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Chris Todd Hittinger's yeast finding is the latest in a spate of recent papers that connect physical or physiological change in an organism to its genetic evolution. One 2004 paper, for example, related jaw development in primates to a mutation in a muscle gene. This growing body of "evolutionary genomics" has implications for understanding how agents of disease, such as those involved in AIDS, make themselves difficult for the host's body and medical caregivers to target. As the field develops, "We'll have a good feeling for how evolution proceeds at the molecular and genetic level," says Hittinger. "It will likely give researchers a better perspective on how organisms will respond to various treatment regimes."
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