Why do cave fish lose their eyes? A Darwinian mystery unfolds in the dark

Natural History, June, 2005 by Luis Espinasa, Monika Espinasa

The gene mapping showed that at least three genes, on three distinct chromosomes, affect eye development, though the exact roles of the genes are still unknown. Borowsky and Wilkens also discovered that one of those genes is closely linked to a gene that regulates metabolic rate (it is even possible, though unproved, that both eye development and metabolism are affected by one gene). Because of the linkage, it is possible that a genetic mutation that improves metabolism could also harm eye development, or be linked to a gene that does. The linkage therefore provides a clue that pleiotropic (or pleiotropic-like) effects might account for the regressive evolution of cave-fish eyes.

A second group of investigators, led by William R. Jeffery, a biologist at the University of Maryland in College Park, has taken great strides in unraveling the history of blindness in Astyanax. In 2000, workers in Jeffery's laboratory transplanted an embryonic surface-fish lens into the optic cup, or eye socket, of a cave-fish embryo, and, conversely, transplanted a cave-fish lens into a surface-fish embryo [see illustration on page 46]. Two months later, the surface fish with a transplanted cave-fish lens had a highly degenerated eye. At the same time, the cave fish previously doomed to eyelessness possessed a large eye with a restored cornea, iris, and lens. Because cells that make up different parts of the eye come from different embryonic tissues, the transplanted lens must have activated genes in the cave fish's own cells.

The significance of their finding cannot be overemphasized. For one thing, it gives no boost to the neutral-mutation theory of blindness in cave fish. Recall that, according to the theory, all genes not being expressed--that is, used as a template for making proteins in the cell--should be accumulating mutations and degenerating. But Jeffery's research showed that, even after tens of thousands of years of evolution in caves, most Astyanax genes that play a role in eye formation remain perfectly functional.

Blindness in Astyanax seems to be caused instead by mutations in a small number of master switches that control other genes and proteins necessary to the development of the eye. Jeffery and his colleagues have isolated one of those master-control genes, a gene known as Hedgehog, or Hh, whose modified expression leads to blindness in cave fish.

Not all the possible pleiotropic effects of Hh in cave fish are known, but suggestive scenarios abound. The Hh gene controls not only the size of the eyes, but also the development of teeth, taste buds, the anterior part of the brain, and other craniofacial structures. Most intriguingly, Hh has an inverse effect on the development of eyes and taste buds: the smaller the eyes, the more taste buds are produced, which undoubtedly lead to an enhanced sense of taste.

Collectively, we have worked with blind cave organisms for more than eighteen years, and one of us (Luis Espinasa) was working with blind cave fish in Jeffery's laboratory shortly after the publication of the momentous work on lens transplants. At the time, Espinasa's research was focusing on the bones surrounding the eye socket in cave Astyanax and how the bones are modified by the presence or absence of eyes. He noted that when a fish develops without eyes, the bones are shifted into the empty socket space, deforming the entire skull. Part of this deformation includes the bones of the nose. The width of the olfactory pit in blind fish increases on average by 13 percent, thus enlarging the surface of the olfactory epithelium, where the chemical receptors are lodged [see illustration on opposite page].