David C. Page
Director, Whitehead Institute
Professor of Biology, MIT
Investigator of the Howard Hughes Medical Institute
Whitehead Institute Director David C. Page has conducted fundamental studies of mammalian sex chromosomes and their roles in germ cell development, with special attention to the function, structure, and evolution of the Y chromosome. In 2003, his laboratory completed the sequencing of the human Y chromosome in conjunction with the Washington University Genome Sequencing Center. Page’s laboratory first reported DNA-based deletion maps of the Y chromosome in 1986, comprehensive clone-based physical maps of the chromosome in 1992, and systematic catalogs of Y-linked genes in 1997.
These genomic studies have led to unanticipated biological insights. The Page laboratory reconstructed the evolution of today's X and Y chromosomes from an ancestral pair of autosomes that existed 300 million years ago. His laboratory discovered molecular evolutionary mechanisms by which the Y chromosome became functionally specialized, in male germ cell development and spermatogenesis. The lab discovered and characterized the most common genetic cause of spermatogenic failure in humans, the deletion of the AZFc region of the Y chromosome.
In conjunction with colleagues at Washington University, the Page lab discovered that most of the Y chromosome’s testis genes exist as mirror-image pairs on massive palindromes. They determined that these palindromes are sites of frequent gene conversion and, thus, that the male-specific chromosome is intensely recombinogenic despite the absence of conventional crossing over to a partner chromosome. Page and colleagues also completed the sequence of the chimpanzee Y chromosome, and through comparisons with the human Y, discovered that both Ys are evolving more quickly than the rest of their respective genomes via continual genetic “renovation.” And most recently, in a comparison of the sequence of the human Y with that of the rhesus macaque, Page revealed that the human Y has lost only one ancestral gene in the past 25 million years. The finding proves that, despite arguments to the contrary, the human Y chromosome is not doomed to eventual extinction.
Having explored the chromosomal basis of human sex reversal (XX maleness) in the 1980s, Page is now turning his attention to the question of germ cell sex determination in mammals, and to the development of the embryonic ovary.
Page is Director of the Whitehead Institute, professor of biology at the Massachusetts Institute of Technology, and Investigator at the Howard Hughes Medical Institute. In 1992, he founded the Whitehead Task Force on Genetics and Public Policy. He is editor (with Matthew Scott) of Current Opinion in Genetics and Development and associate editor of the Annual Review of Human Genetics and Genomics.
Page trained in the laboratory of David Botstein, at MIT, while earning an M.D. magna cum laude from Harvard Medical School and the Harvard-MIT Health Sciences and Technology Program.
- Mapping and cloning the Y chromosome
- Publishing the complete sequence of the Y chromosome
- MacArthur Foundation Prize Fellowship (1986)
- Searle Scholar’s Award (1989)
- Science magazine’s Top 10 Scientific Advances of the Year (1992)
- Amory Prize from the American Academy of Arts and Sciences (1997)
- Curt Stern Award from the American Society of Human Genetics (2003)
- Elected to the National Academy of Sciences (2005)
- Elected to the Institute of Medicine (2010)
- March of Dimes Prize in Developmental Biology (2011)