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Natural Selection Cuts Broad Swath Through Fruit Fly Genome

By Nicholas Wade; Published: September 20, 2010

A new exploration of how evolution works at the genomic level may have a significant impact on drug development and other areas of medicine.

The report, published in Nature last week, offers new evidence in a longstanding debate about how organisms evolve. One well-known path to change is a heavily favorable mutation in a single gene. But it may be well known only because it is easy to study. Another path is exploitation of mildly favorable differences that already exist in many genes.

The question has considerable practical importance because if complex traits, including susceptibility to disease, are influenced by just a few genes, then it should be easy to develop treatments that target the few genes’ products. But if tens or hundreds of genes are involved in each trait, the task may be close to impossible.

Theorists have argued over this point for years, but researchers have been able to address it only recently. With advanced DNA decoding machines they can now afford to decode every DNA unit in sample genomes of a population undergoing an evolutionary change.

Three biologists at the University of California, Irvine, Molly K. Burke, Michael R. Rose and Anthony D. Long, followed populations of fruit flies through 600 generations and studied the whole genome of some 250 flies in order to see what kinds of genetic change they had undergone.

The flies live in populations of 2,000 or so, each kept in a shoe-box-size container and fed a mixture of bananas and corn syrup of which they never seem to grow tired, Ms. Burke said.

With each generation the researchers picked the flies that hatched earliest to be the parents of the next generation, and by the end of the experiment, the time to hatching had become 20 percent shorter. The question to be answered was how this happened.

The conventional view is that evolutionary change is generally mediated by a favorable mutation in a gene that then washes through the whole population, a process called a hard sweep because all other versions of the gene are brushed away. The alternative, called a soft sweep, is that many genes influence a trait, in this case the rate of maturation, and that the growth-accelerating versions of each of these genes become just a little more common. Each fly has a greater chance of inheriting these growth-promoting versions and so will mature faster.

In sequencing their subjects’ genomes, the researchers found that a soft sweep was indeed responsible for the earlier hatching. No single gene had swept through the population to effect the change; rather, the alternative versions of a large number of genes had become slightly more common.

The debate about whether evolution proceeds by altering one or many genes started 90 years ago among the three founders of population genetics, Ronald Fisher, Sewall Wright and J. B. S. Haldane. Haldane favored the single mutation mechanism, but Fisher and Wright backed multiple gene change. The fruit fly experiment “is a total vindication of Wright and Fisher and a major defeat for Haldane and a lot of conventional geneticists who have sided with him,” Dr. Rose said.

The demise of the Haldane view “is very bad news for the pharmaceutical industry in general,” Dr. Rose said. If disease and other traits are controlled by many genes, it will be hard to find effective drugs; a single target would have been much simpler.

Richard Lenski, an evolutionary biologist at Michigan State University, said the finding that natural selection had worked by changing gene frequencies in the fruit fly experiment was very interesting. “This is really the first time that the process has been directly documented across an entire genome of a multicellular organism,” he said.

Dr. Lenski does similar experiments with bacteria which, unlike fruit flies and people, multiply by fission and have a single genome, not a double one that is mixed and matched every generation. In one-genome organisms, hard sweeps by a single novel gene are common. Hard sweeps do occur in sexually reproducing organisms like people and fruit flies, but soft sweeps may be more usual.

Jonathan Pritchard, a geneticist at the University of Chicago, wrote this year that there seem to have been surprisingly few hard sweeps in recent human evolution, and that therefore much early human adaptation to novel environments since the dispersal from Africa may have been mediated by soft sweeps. In addition, soft sweeps could explain the apparent speed of human evolution, because they work on the genetic variation already present in a population, without having to wait for a novel mutation to arise. The fruit fly experiment shows that natural selection can indeed work through soft sweeps, at least for certain traits.

This article has been revised to reflect the following correction:

Correction: September 22, 2010

An article on Tuesday about research into evolution at the genomic level misstated the academic affiliation of Richard Lenski, an evolutionary biologist. He is at Michigan State University, not the University of Michigan.

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