Molecular mechanism for evolution

Molecular mechanism for evolution described

November 26, 1998

Researchers at the University of Chicago have discovered the first molecular mechanism for promoting evolutionary change in response to the environment. The mechanism works by allowing multiple small genetic variations to accumulate and then expose themselves when that organism is under environmental stress.

For the first time we have a molecular mechanism that explains how organisms that have stuck to the same morphology for eons can evolve new traits that help them adapt to changing conditions, says Susan Lindquist, PhD, professor of molecular genetics and cell biology at the University of Chicago, Howard Hughes Investigator, and lead author of the paper in the November 26, 1998 issue of Nature .

The expression of these variations depends on a protein called heat shock protein 90 (Hsp 90) that normally keeps certain inherent genetic variations in a population silent, but can reveal them during times of stress--such as climate change.

All organisms make heat shock proteins, also known as chaperones, in response to high temperatures. It is the chaperone's job to prevent other proteins from getting into trouble--misfolding or losing their unique shapes. Once this happens, the misshaped protein can no longer function, and regular cellular metabolism cannot proceed.

"Hsp 90s charges are special. They are proteins called signal transducers, which regulate development and cell differentiation. Hsp 90 keeps them poised and ready for action. Signal transducers control morphological development. They make sure the right part grows at the right spot at the right time. That's why you have two hands and two feet instead of four hands," says Lindquist.

During times of stress, however, all sorts of proteins start to unfold, and Hsp 90 is recruited away from its normal duties to help out. The signal transduction pathways are then sensitized to small genetic variations that otherwise go unnoticed, and development takes a twist.

"Then the natural variations inherent in an organism's DNA can produce major changes in body plan, which can be passed on to offspring. This sounds like a very bad thing, and no doubt it is for most of the individuals," says Lindquist. "But for some, the changes might be beneficial for adapting to a new environment. Cryptic genetic variations exposed in this way become the fodder for evolution."

Lindquist and Suzanne Rutherford, a postdoctoral fellow, demonstrated that reducing levels of Hsp 90 allowed natural genetic abnormalities hidden in fruit fly populations to suddenly appear.

Using an Hsp 90 mutation, Rutherford crossed flies with only half the amount of functional Hsp 90 with different fly populations. She noticed that a few of the progeny from these crosses were different; they had thick veined wings, strange bristle configurations, or deformed eyes or legs. The same results were obtained in wild-type flies with a drug that inhibits Hsp 90 function.

"When she crossed the defective offspring, she got an even greater number of curious progeny. Lindquist and Rutherford also noticed that the types of abnormalities that kept cropping up were specific to particular populations. For example, when the Hsp 90 deficient flies were crossed with one population, the progeny had odd-shaped wings. When they bred the flies with another stock population, some of the offspring had bristles and leg-like structures for antennae. This suggests that there are population-specific hidden genetic oddities," explains Lindquist.

After several rounds of inbreeding, as many as 90 percent of the flies exhibited visible abnormalities. The fact that this took several generations indicates that we had to get several different genetic variants together in order to get a particular abnormality, Lindquist says.

But after multiple rounds of breeding, Hsp levels were back to normal even though the abnormalities persisted.

Once the frequency of the odd variants was enriched by selective breeding (this was how we mimicked the possible effects of natural selection) the traits no longer depended on decreased Hsp 90, Lindquist explains. That means that if such abnormalities should happen to be valuable, they can be stabilized in the population without requiring constant changes in Hsp 90 or the environment.

Lindquist speculates that Hsp 90 may be a key player in controlling the alternation between long periods of genetic stability and the sudden bursts of morphological change seen in the fossil record during times when the earth was undergoing major climate changes.

"The way that Hsp 90 covers and uncovers hidden genetic variations provides a very plausible mechanism for revealing variation for natural selection to act upon. Proving that it actually functions on an evolutionary time scale, however, will be no easy task," says Lindquist.

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