Conquering evolutionary conflict
Harmit Malik explores the genetic ‘arms races’ that drive evolution and help provide insight into cancer and other life-threatening diseases
From Dr. Harmit Malik’s point of view, evolution is sometimes like a long-lived dispute between neighbors. One neighbor plows his sunny back yard into a vegetable patch. The other neighbor, who longs for a shade garden, plants a tree that grows so tall that it casts darkness over his land and the sun-loving tomatoes next door. So the first neighbor cuts down the tree.
The situation is much the same in nature, where examples of competing survival instincts — such as the situation between predators and prey or viruses and the hosts they infect — often result in evolutionary change. Genes and proteins within our own bodies even can participate in this competition, events Malik describes as genetic arms races. In most cases, the sources of these conflicts have yet to be discovered, but once identified could reveal previously unknown examples of adaptation in response to potential sources of infection or even deadly diseases like cancer.
A new generation
If this sounds complex and far-reaching, it is. With a background in molecular and evolutionary biology, Malik conducts research that puts him at the forefront of a new generation of fundamental scientists. His postdoctoral studies at Fred Hutchinson exhibited extraordinary promise and led to offers from many world-class research institutions, including the center, where he is now among its newest faculty members.
“Evolution loves to optimize,” said Malik, who joined the faculty last year. “Once an optimal state is reached, there is little tendency to tinker with it. But the arms races we are finding suggest that there are ongoing competing interests that are driving change, some of which may have consequences for human health.”
Using this novel approach to probe for clues to human disease, Malik’s lab recently discovered that an unusual defense mechanism that the body uses to attack the AIDS virus evolved millions of years before the existence of HIV. In this striking example of a biological tug-of-war, the defense system has provoked the virus into evolving strategies to evade it. The findings may provide insight into why the disease progresses in some infected individuals and not in others.
Other projects in Malik’s lab involve the evolution of proteins that conduct some of life’s most essential functions, such as cell division and the packaging of the DNA blueprint into chromosomes.
Malik points to cancer as an extreme example of the negative consequences that could result from conflict that is driven by selfish survival interests.
Unique research perspective
“Humans are multicellular organisms in which the growth of cells must be precisely controlled,” he said. “Tumors are a clutch of cells that ignore these controls. From an evolutionary perspective, it is an advantage for the cancer cells to grow at the expense of their healthy neighbors — but it’s a short-lived benefit because evolutionary success depends on the whole organism.”
Although evolution is a subject that preoccupies numerous scientists, Malik’s deep knowledge of multiple fields of biology puts him in a unique position of strength to answer many important questions, said Dr. Mark Groudine, Fred Hutchinson’s deputy director.
“Harmit is an extraordinary intellectual with broad interests and deep knowledge in many fields, and he has a uniquely creative and fearless approach to his research,” he said. “This has enabled him to make unexpected discoveries, and his ideas are having an enormous impact on the field.”
As further testament to his accomplishments and diverse interests, Malik is a recipient of a 2004 Sloan Research Fellowship in Evolutionary Biology from the Alfred P. Sloan Foundation and a 2004 Kimmel Scholar Award from the Sidney Kimmel Foundation for Cancer Research.
The hunt for evolving genes
To hunt for rapidly evolving genes that may yield insight into human disease, Malik examines closely related species to identify equivalent genes from humans and their close relative, the chimpanzee. He looks for those genes whose DNA sequences differ in significant ways among the species. This suggests that an arms race might be taking place because nature has not settled on an ideal form. Once candidates are identified, the researchers must hunt for the opponent or opponents in the conflict in order to develop hypotheses to explain why the adaptive evolution is taking place.
Malik’s research interests evolved from diverse educational experiences. Born and raised in India, he earned an undergraduate degree in chemical engineering from the prestigious Indian Institute of Technology in Mumbai. As a graduate student at the University of Rochester, he first became interested in the study of molecular evolution. He continued in this field when he joined Dr. Steven Henikoff’s lab at Fred Hutchinson for postdoctoral training in 1999, where his exceptional research earned him a job offer from the Basic Sciences Division, which has rarely hired from within.
Despite competing offers from universities with top-ranked departments of zoology and evolution, Malik chose to study at Fred Hutchinson among faculty best known for their strengths in probing proteins, genes and cells. He described the collegial atmosphere and the overall research excellence of Fred Hutchinson as the major draws, as well as the proximity to a strong zoology department at the University of Washington.
He doesn’t have any worries that the differing interests of his laboratory neighbors will result in perpetual conflict. Rather, he expects the blending of research viewpoints will result in the productive evolution of his own career.
“Evolutionary biologists have made enormous insights into why genes and genomes have evolved the way they have,” he said. “On the other hand, molecular biologists have been able to provide exquisite detail into how proteins function. My research hopes to draw from both disciplines, to simultaneously explain both the ‘why’ and the ‘how’ of the mystery of rapidly evolving genes.”
Barbara Berg, Ph.D., is senior science writer for Fred Hutchinson Cancer Research Center.
Disease breakthroughs from fundamental research need your financial support
By studying the basic principles of genes, proteins and cells, fundamental researchers like Dr. Harmit Malik often unearth valuable clues about defects that can cause diseases, such as cancer. Fundamental research at Fred Hutchinson has led to major cancer breakthroughs, including:
- A diagnostic test to show if a woman with breast cancer would benefit from aggressive chemotherapy
- A new diagnostic test for lupus, the first screening breakthrough for the disease in 50 years
- Insight into why infection with human papilloma-virus is a major risk factor for cervical cancer, which contributed to a development of a vaccine
Your donations provide critical support for promising studies like these. To make a donation to our Fundamental Research Initiative, call us at (206) 667-4399 or (800) 279-1618 or visit our Web site at www.fhcrc.org/donating/donate_now.html.
