Geneticist Pardis Sabeti

Evolution and genetics once seemed worlds apart. While evolutionary biologists generally charted the paths that organisms had taken in the past, geneticists attempted to catalogue the present state of a species' genetic makeup, often with the aim of curing some human diseases in the future. By developing a system to analyze genetic information through an evolutionary lens, Harvard scientist Pardis Sabeti has helped to bridge the divide between these two scientific disciplines. Now she hopes that these new tools may one day help eliminate some of the world's deadliest diseases.

Scientists have known for more than a century that evolution proceeds through a process of natural selection. Traits that are beneficial to an organism and improve that individual's chances of survival and reproduction are more likely to be passed on to future generations. Traits that are detrimental to survival are less likely to be passed on.

The concept of genes and their relation to an organism's traits and to inheritance was first suggested by Gregor Mendel in the 1860s, based on his studies of pea plants. Despite tremendous advances since then in our understanding of what genes are and how they function, the way in which genes are selected for and become more common in a population has remained something of a mystery. In addition, hypotheses regarding the path of evolutionary change have proven difficult to test.

Pardis Sabeti helped to resolve these two mysteries by developing a method to analyze the human genome in search of the signs of natural selection. Although the genetic difference between one person and the next is a scant 0.01 percent, the differences that exist can be telling. Scientists think that common genetic variations that have arisen relatively recently are clear signs of the work of natural selection. The method that Sabeti developed analyzes such common variations to determine how long ago they arose in the population. In this way, she has identified several variations that have likely been favored by evolution. As an example, Sabeti points to the mutation that causes sickle cell anemia. Although this mutation causes disease in people who inherit a copy from both parents, it offers malarial resistance to individuals who possess only one copy. Indeed, Sabeti found that the sickle cell mutation became prevalent quite recently in evolutionary terms in regions were malaria is prevalent.

Sabeti has more recently turned the focus of her analysis from human evolution to the evolution of disease-causing organisms, including the parasite that causes malaria. She hopes that by identifying regions of a parasite's genome that have been favored by evolution, the analysis might also reveal genetic vulnerabilities that could be more effectively targeted by medicine. The malaria parasite and many other disease-causing microorganisms have proven their ability to adapt quickly and become resistant to medications used to fight them. Sabeti's hope is that by identifying a vulnerability in this process, scientists will one day be better able to fight, and perhaps eliminate, diseases including malaria, tuberculosis, and HIV/AIDS.

To learn more about the connection between natural selection and genetics, check out Genetic Variation, The Common Genetic Code, Mendel's Laws of Genetic Inheritance, and Some Genes Are Dominant.

To learn more about the evolution of the sickle cell mutation in response to malaria, check out A Mutation Story.

To explore the rapid evolution of microorganisms, check out Microbe Clock.

• What did Pardis Sabeti figure out? Why do you think it was considered a scientific breakthrough?
• Why do you think she describes her breakthrough as a "wonderful scavenger hunt"?
• What is meant by the term "resistant" in the context of disease-causing organisms?