From the issue dated May 26, 1995
Revelations From Fruit Flies
Geneticists' research on freakish eyes may bring revisions in some tenets of evolutionary biology
By Peter Monaghan
By creating freakish fruit flies with eyes on unusual parts of their bodies, a team of Swiss geneticists appears to have rewritten some important tenets of developmental and evolutionary biology.
They have shown that in species as varied as flies and mice, a common genetic key triggers the development of eyes of vastly differing construction.
They also have provided strong evidence that, contrary to common belief, the eyes of animals as unrelated as vertebrates and invertebrates evolved more than half a billion years ago from a common ancestor.
Their findings, published in March in Science magazine, are being hailed by researchers in genetics, developmental biology, and other fields. In an article in Natural History, Stephen Jay Gould, professor of zoology at Harvard University, calls the team's work "the most exciting event in evolutionary theory during the past decade."
The Swiss team was led by Walter J. Gehring, professor of developmental biology and genetics at the University of Basel's Biozentrum, an interdisciplinary research-and-teaching center.
He is well known among fruit-fly geneticists both as a basic researcher and as a developer of techniques for advanced genetic screening and engineering. Still, he admitted in an interview, he was surprised by the extent of the findings. "It came as a total surprise that there is so much shared between vertebrates and invertebrates," he said.
The experiments were suggested by a finding that Mr. Gehring and three research associates published in Science last August, itself greeted as extraordinary, that the fruit-fly gene known as eyeless matched almost exactly a gene that is crucial to eye development in mice, and another gene with a similar role in humans.
The Drosophila fruit-fly gene is called eyeless because mutations result in defective eyes or no eyes at all. The equivalent mouse gene is Small eye; mutations result in undersized eyes. The human equivalent is Aniridia; defects cause malformations of the iris and other eye parts.
Mr. Gehring wondered how much control the genes had over eye development. To find out, he and two colleagues -- Patrick Callaerts, a postdoctoral fellow, and Georg Halder, a doctoral candidate -- induced the eyeless gene to be switched on in fruit-fly tissues where it normally is not.
When the larvae hatched, the eyeless gene had overridden the normal growth patterns in wings, legs, antennae, and other body parts, causing as many as 14 eyes to grow in places where, obviously, they normally don't.
Because the eyes were fully developed, Mr. Gehring and his colleagues could conclude that the eyeless gene is what he and some other geneticists call a "master-control gene." Eyeless appears to activate the cascade of biochemical events that take place in eye development.
Next, Mr. Gehring and his colleagues induced the Small eye gene in mice to start the process of eye development in various parts of fruit-fly embryos.
In an even more surprising result, fully developed eyes -- fly eyes, not those of mice -- grew in unfamiliar places. As Mr. Gehring put it, genetically "these flies understand mice."
Finally, the Swiss team was able to suggest, to the astonishment of colleagues, that because homologous, or equivalent, eye genes are found in a variety of species with different eye constructions, those genes must have a common ancestor. Such a gene would date back more than 500 million years and would have been conserved when, much later, insects and mammals evolved.
The researchers speculated that the gene has been conserved, perhaps across all species with eyes or more primitive visual systems.
This would be astounding, because the eyes of mice and flies, for example, are so different. Mice have simple, single-lens eyes; fly eyes are compound, constructed of 800 eyelets, or ommatidia.
"This was contrary to all our expectation on morphological grounds," said Mr. Gehring.
Mr. Gould of Harvard agreed in his article, saying the homology was so unexpected that "such a contribution from common ancestry would have seemed almost risible as few as five or ten years ago." He characterized the finding as "downright revisionary in forcing a rethinking of many previous certainties."
The reigning theory about eye evolution in animals has long been that the widely varied types of eyes in the animal kingdom -- making up, as Mr. Gould put it, a "riotous display of diversity" -- must have evolved separately.
College textbooks talk of eyes as the classic case of "convergent" evolution. This theory holds that different eyes evolved as many as 40 separate times, along similar but independent evolutionary pathways, beginning from primordial eyespots of light-sensitive cells.
That theory has prevailed even though, as Mr. Gehring said, "This was very improbable in terms of Darwinian theory," which would suggest that so complex a structure as the eye could not arise more than once by random selection. "Our finding strongly implies -- it doesn't prove -- that the prototype was invented only once."
In his Natural History article, Mr. Gould speculated that evolution theorists will now search for better explanations of other purported cases of convergence.
Mr. Gehring theorized that, after the eye prototype proved an evolutionary success, its biochemical machinery was passed on to the ancestors of modern animals. The successors of those primitive visual systems, he believes, have "converged and diverged depending on selective pressure."
Mr. Gehring and his colleagues are now preparing a third article for Science, about evolutionary aspects of their work.
To fill out the new understanding, they and collaborators elsewhere, including at the National Institutes of Health, are hunting for other homologs of eyeless. They have already found some in species as varied as squid and primitive marine worms. The goal, Mr. Gehring said, is "to get as close to the prototype as we can."
They will compare the gene's role in different species and will see if it plays a role in single-cell organisms.
The findings about the "master-control gene" status of eyeless are galvanizing other geneticists, too.
Charles S. Zuker, professor of biology at the Howard Hughes Medical Institute at the University of California at San Diego, said the Swiss research "has led to a tremendous amount of speculation." He called the findings "quite incredible."
It was predictable from the study of genetics over the past decade that vertebrates and invertebrates could have almost identical genes playing similar roles, he said. What was striking was that organs as different as fly eyes and human eyes appeared to result from a homologous genetic process.
Gerald Rubin, a professor of genetics at the University of California at Berkeley and an investigator at the Howard Hughes Medical Institute, said: "What is impressive about it is that it is a single gene that causes the formation of a whole organ. This is a higher level of influence for one gene than had been demonstrated before."
Mr. Gehring believes the gene is at the top of a hierarchy of some 2,500 genes that engage in the process of eye formation.
While researchers have in the past induced cells to develop briefly but abortively in odd locations, Mr. Rubin said, the Gehring team had induced tissue that normally would have become one kind of structure to become another complete organ.
The out-of-place eyes appeared to be normal and fully formed. They had bristles, ommatidia, and pigment cells. Their photoreceptor cells even responded to light.
Mr. Gehring and other researchers now believe that they have a key point of entry that will permit them to document events "upstream" and "downstream" from the triggering of eyeless.
That potential, said Mr. Zuker, is "spectacular. It opens up a lot of very important science."
It was an almost accidental discovery that began the Swiss team's series of experiments. Two researchers in Mr. Gehring's laboratory -- Rebecca Quiring, a graduate student, and Uwe Walldorf, a postdoctoral fellow -- stumbled across the homology between eyeless and Small eye while looking for something else.
Their finding, and the suggestion that the homologous genes could be key actors in eye development, rang a bell for Mr. Gehring. He recalled a mysterious phenomenon he had noticed 30 years ago as a doctoral student at the University of Zurich.
Fruit-fly-wing cells, grown in a laboratory culture, mysteriously had switched to bright-red eye cells. "I'll never forget that," he said. "It was a very rare event. It happened only once, but it showed me that it could happen." He still has a color slide of the phenomenon, which he dubbed "transdetermination."
Research techniques at the time were not adequate to investigate or explain it. Still, he was confident of what he had seen, and last year he predicted to colleagues that he could get eyes to develop in odd places. Mr. Rubin said few Drosophila geneticists anywhere would have given him much chance of success.
Now Mr. Gehring has assigned some of his research assistants, armed with the new findings, to figure out how transdetermination happens.
Meanwhile, he said, he was willing to bet that at least some of the fruit flies' oddly located eyes are neurologically wired so that they actually function as eyes.
He doesn't give eyes on legs and wings much chance of making the necessary connections but holds out more hope for the ones closer to the head, particularly those on the end of antennae.
"Nobody wants to bet against me any more, even a small bottle of wine," he said. "But I could be wrong."
Copyright © 1995 by The Chronicle of Higher Education
