Mutation effects often depend on genetic milieu

Other genes at least as important as environment, study shows

The genetic differences that make each individual unique may be even more important than scientists previously thought, a new study of fruit flies suggests.

WING AND A MUTATION A mutation in the scalloped gene alters the wings of two different strains of fruit flies from their normal, or wild-type, appearance (left). The genetic background of the Oregon R (center) and Samarkand (right) strains was the main determining factor in how the mutation affected the wing shape. I. Dworkin

In two strains of the fruit fly Drosophila melanogaster, underlying genetic makeup outweighs any other factor in dictating how a specific mutation will affect wing shape, geneticists Sudarshan Chari and Ian Dworkin of Michigan State University in East Lansing reported in Washington, D.C., April 8 at the 51st Annual Drosophila Research Conference.

Researchers have known that the environment has the potential to influence a mutation’s effects. But the new study suggests that a vast majority of the time, the interaction between two mutations is influenced by all the other genetic variations in an organism’s DNA — what scientists refer to as genetic background.

To determine the importance of genetic background, Chari and Dworkin compared the effect of a mutation in a gene called scalloped on two common laboratory strains of Drosophila melanogaster. The Oregon R strain is often used in genetic experiments, while Samarkand-strain flies are common research subjects for evolution and ecology experiments.

The wings of both flies are normally long and oval. But while a mutation in the scalloped gene turns the wings of Oregon R flies into stubby, multilobed nubbins, the same mutation in Samarkand flies results in long, rectangular wings.

Interactions between scalloped and another gene called optomotor blind are also influenced by the genetic background, the researchers discovered.

But it wasn’t clear if underlying genetic makeup is important only in rare cases or if it is a major factor influencing how a mutation may affect an organism. The researchers did experiments to find other mutations that interact with scalloped and alter wing shape. About 75 percent of those mutations had differing effects in the two strains. The rest of the mutations had the same effect in both strains.

If the finding holds in humans, it could help explain why some people who carry a particular genetic variant develop disease while others with the same variant stay well, or why drugs have variable effects in different people.

This places a number on the importance of genetic diversity, says David Angelini, a developmental geneticist at American University in Washington, D.C. But the magnitude of the effect may vary from species to species, he says.

“Genetic diversity is going to be important in all organisms. Exactly what the number will be, I don’t know,” Angelini says.

Scientists who perform experiments in only one strain of fruit fly may not uncover all the genetic interactions that shape an organism, he says. “What it might mean is that we are some missing some players in these interactions.”

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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