HARVARD GAZETTE ARCHIVES
Genes in conflict:
David Haig looks at internal genetic warfare
By William J. Cromie
Most people think of genes as molecules that make you more or less fit for survival. In healthy people, genomes are seen as well-functioning machines where all the parts work together for a common good.
That's not necessarily so, believes David Haig, a newly tenured professor in the Department of Organismic and Evolutionary Biology. "I'm interested in situations where genes in an individual have different fitnesses and can come into conflict with each other," he says.
He's not talking about genes with different functions battling for a top spot in your genome, but identical genes with different "attitudes."
All genes except those that determine sex come in pairs, one inherited from your mother and one from your father. In most cases, the result of such pairing never changes, there is no conflict. If you receive a gene for blue eyes from your mom and one for brown eyes from your dad, you wind up with brown eyes. If you inherit a gene for blue eyes from your dad and one for brown eyes from your mom, you still wind up with brown eyes.
But in genes that interest Haig, parental origin makes a difference. The gene does one thing if it comes in an egg cell and another if it comes in a sperm cell. What maximizes the fitness of the one is different from what maximizes the fitness of the other.
Haig cites the example of pregnancy. Nutrients are transferred to the fetus through the placenta, and the more food it receives, the healthier the baby will be. But that comes with a cost to the mother. The more nutrients she supplies, the less energy she has to devote to other offspring, and the more vulnerable she becomes to disease. Therefore, the genes that a fetus receives from its mother are most interested in mom's survival and reproduction in the future.
Genes from the father, however, take a different view. They demand the most from the mother during a pregnancy and are less interested in her future reproduction. There's even evidence that paternal genes are particularly active in the growth of the placenta, which would increase the amount of nourishment the fetus receives but increase the cost to the maternal genes. Therein lies the conflict.
Born to be a biologist
Naomi Pierce, Hessel Professor of Biology and Curator of Lepidoptera, remembers the first time she met Haig. "I was struck by his remarkable combination of unreserved affability and academic brilliance," she says. "He can explain phenomena ranging from crocodilian sex determination to genomic imprinting in the most lucid and engaging manner. He is particularly well known for his evolutionary explication of the latter - situations where a gene has a different pattern of expression depending on whether it is inherited from an individual's mother or father. His work has been important in explaining how this can lead to unusual aspects of mammalian development, including a number of human diseases."
These diseases include various forms of childhood cancer and a rare malady that produces dramatic overgrowth of a fetus. Many of these genes are involved in cell growth, and cancers are, basically, the uncontrolled growth and progression of cells.
Although born to be a biologist, Haig, now 44, didn't start out to work on such theoretical questions. His first interests were birds and plants. He was born in Canberra, the busy capital of Australia, which was more like a quiet country town then. Flocks of parrots used to fly in to drink at the family fishpond, and that got him interested in bird watching at the age of 7. His mother taught high school biology, and she added fuel to his interest in birds and plants.
Haig did undergraduate work at Macquarie University in Sydney, and entered graduate school with the idea of getting a Ph.D. in plant ecology. As he got into his studies, however, he became interested in theoretical questions.
"As an undergraduate, I read a number of great papers on evolutionary biology written by Robert Trivers, who was then at Harvard," Haig recalls. "My interest in genomic imprinting started with these papers. Trivers is now at Rutgers University, and since coming to America, we're gotten to be good friends."
For his Ph.D., earned in 1989, Haig did a theoretical thesis on the life cycles of vascular plants. He then went to Oxford University for two years of postdoctoral work. Afterwards, Pierce nominated him for the Harvard Society of Fellows.
Haig arrived at Harvard in 1992, and describes the fellowship as "a wonderful three years." He was appointed a tenured professor last year.
"David is a person of enormous integrity who is deeply thoughtful about ethical, political, and religious views of all kinds," comments Pierce. "Not only is he one of the most original evolutionary theoreticians of his generation, but he is genuinely kind and generous to everyone around him. Besides, he is fun to relax and have a drink with, and he tells marvelous stories."
Clerking couldn't hold him
Haig's road from undergraduate to tenured professor was not as straight as it is for most people. After earning his bachelor of science degree, he decided to take time out "to learn about other things in life." After working as a dishwasher, he landed a position as clerk for the New South Wales State Government.
"I had a rubber stamp and it cost people money for me to stamp their legal documents," he explained. "I learned a lot about the world, life, and people during the three years I took off. But, after a couple years of stamping documents, I decided that academia was a better place to be. It's not as carefree as the life of a clerk, but it's more intellectually stimulating."
Now that he has reached a peak in academia, Haig says he "would like to get back to plants. Genomic imprinting occurs in them, too," he points out. "There is also a lot of loose ends in my thesis work, fascinating things about plant life cycles that I'd like get back to."