A House of Mirrors
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As Page and his group have readied their findings for their next series of articles, set to begin publication later this year, their workplace itself looks like a map. Three long sheets of white paper hang on a huge bulletin board, creating a paper trail of the group's journey along the Y chromosome. At several points, the word "GAP" is scrawled inside circles in yellow highlighter next to stretches of terra incognita: DNA still undefined. Some of the circles are X'ed through—simple shorthand that marks the group's progress.
Other researchers around the world, though not many, are also intrigued with Y and by the details on those wide ribbons of paper. "It's a smallish field," says Bruce T. Lahn, a former graduate student of Page's who recently was named an HHMI investigator at The University of Chicago. And, no wonder. Y has a small number of genes, and the genes are not implicated in many human diseases. The chromosome's small size might suggest that it's a fast read, but short books aren't always the easiest to grasp. Mapping and identifying the chromosome's active genes has been maddening, in fact, as investigators have found themselves hampered by the presence of multiple gene copies and many inert genes. "Mapping the Y chromosome," says Page, "is like walking into a house of mirrors for a few minutes and, when you leave, being asked to draw a floor plan."
Figuring out this confusing layout and understanding the design is a tantalizing puzzle for Page, whose office is lined on three walls with shelves filled with textbooks and binders carefully organized by subject and with journals clustered according to date and publication—a setup that would make a librarian beam. Gazing out his window toward an area of Cambridge where several biotechnology companies involved in genomics are headquartered, Page rattles off a series of questions that hint at semantic implications: "Why do we call sex chromosomes sex chromosomes? What puts the sex in sex chromosomes? What do the sex chromosomes have to do with sex, being male and female?"
His phrasing is no idle wordplay; nor are these the same question. The Y chromosome's idiosyncrasies need to be examined simultaneously from slightly different perspectives. "In the same breath, we can think about the gene's relationship to making eggs and sperm, the role of mutations in that gene to infertility, and that gene's arrival on the sex chromosome in evolution," Page says. All of these are roles that researchers began exploring in the early 1980s and still haven't fully explained.
