Sept. 9, 1998

An evolutionary biologist at the University of Rochester has put forth a new theory on the genetic foundations of adaptation, the process whereby a species responds to a changing environment. H. Allen Orr suggests that, faced with environmental change, organisms can evolve through a mix of many minute genetic tweaks, a lesser number of moderate changes, and a few major mutations. The new idea runs counter to standard theory on evolutionary genetics, which holds that only the tiniest of genetic changes contribute to adaptation. The work is published in the August issue of Evolution, due out this month.

Orr's is the first new theory on the genetic architecture of adaptation since biologist R.A. Fisher's 1930 assertion that adaptation is solely the result of minor changes in genes -- a view that's come under fire over the last 15 years. Orr's new work is the most thorough attention given to the genetic basis of adaptation in decades, says Nick Barton, a noted evolutionary biologist at the University of Edinburgh in Scotland.

"Allen Orr gives an admirably thorough treatment, which is much more sophisticated than Fisher's brief argument," Barton says. "Overall, I think that Orr's paper will stimulate a good deal of theoretical and empirical work on what is a key question in evolution: what kind of genetic changes contribute to adaptation."

Adaptation, which can take thousands of years to complete, takes forms ranging from the subtle to the mammoth. An example of the process is a species of fruit fly transported to an isolated island in the Indian Ocean hundreds of thousands of years ago. Over the millennia, the tiny fly's isolation from other populations permitted so much genetic divergence -- enough even that the island species now subsists on a fruit that's toxic to all other species -- that it's now considered a distinct species, incapable of breeding with its ancient brethren.

While almost all scientists accept the theory of evolution, there's very little understanding of how it actually occurs on the "front lines" of genetics. Fisher's theory, generally considered the standard-bearer on the subject since 1930, holds that adaptation results from the accumulated effects of many tiny genetic mutations, such as changes in single DNA bases with a very limited effect. Orr, an associate professor of biology, likens Fisher's belief that major mutations are always deleterious to random tinkering with the innards of a television.

"If you open your television and make some minor adjustments, you might not cause any problems, and there's a chance that you might even make things better," Orr says. "But if you go in and rewire everything and make a bunch of major changes, the chances aren't good that it'll have a positive effect."

However, researchers began poking holes in that argument in 1983, and now Orr has turned it on its head by showing that the distribution of mutations causing adaptation neatly fits an exponential curve: While few major mutations are needed, the number of more minor mutations rises exponentially with their genetic insignificance. Orr's theory is based on mathematical modeling and computer simulations, and assumes that a population is well-positioned to adapt to environmental pressures. He now plans to use a common laboratory technique called quantitative trait locus, or QTL, analysis -- capable of examining how species' genetic compositions differ -- to examine whether his theory holds up.

"Historically, the genetic basis of adaptation has been a neglected area of study," Orr says. "We don't have answers to some very fundamental questions: Does adaptation require minor changes in many genes, or just a few whoppers? To what extent is each of these individual changes responsible for the divergence of species? What are these critical genes that get altered in the course of adaptation? Hopefully now we'll start to get answers to some of these questions."

Orr's research is sponsored by the National Institutes of Health and the David and Lucile Packard Foundation.

CONTACT: Steve Bradt, (716) 273-4726.