From tracing the evolution of sex chromosomes to revealing the intricacies of the origins of sex determination, David Page has spent his career exploring the myriad forces and defining moments that have shaped who we are and how we got here.
Page got his first taste of what research was all about as an undergraduate, when he landed a summer job at the National Institutes of Health. There Page learned how to design experiments to answer scientific questions. "I became obsessed," he recalls. "I was finally coming to grips with the fact that scientists are the first people in the world to know things, and I found it absolutely intoxicating." While Page was a medical student at Harvard and the Massachusetts Institute of Technology, he first encountered the Y chromosome, spurring his research for the coming decades and culminating in the completion of the human Y chromosome sequence.
Page discovered large, mirror-imaged genetic sequences on the human Y chromosome that enable the Y to maintain its genetic health—and ensure its own survival—by swapping genes with itself. The finding should have dispelled the then-popular notion that the Y was losing genes at a rate that would lead to its eventual extinction. Somewhat surprisingly, the "dying Y" theory persisted, but Page's recent work has made it increasingly uncomfortable for those who cling to it.
The lab has been conducting a series of cross-species comparisons of Y chromosomes that confirm that this oft-maligned chromosome is alive and well and here to stay. An examination of the human and chimpanzee Y chromosomes shows that both are evolving more quickly than the rest of their respective genomes. A recent comparison of the human Y chromosome and that of the rhesus macaque indicates that gene loss on the human Y actually ceased at least 25 million years ago. The sequencing of even more Y chromosomes from divergent mammals such as mouse and bull promises to "reframe the debate for the 'rotting Y' crowd," he says.
Page is also undertaking an ongoing study of germ cells, unique among all other cells in their ability to halve their chromosomes via meiosis. In both males and females, primitive germ cells arise in the developing fetus and make their way to the gonads, where they ultimately give rise to eggs and sperm. The sexual identity of germ cells is determined by the timing of their entry into meiosis. Page has identified several critical players in the initiation of meiosis, which opens the door to enormous insights in the understanding of germ cell sex determination and development in both males and females.
