The genes behind vision's palette.

The genes behind vision's palette

The human brain visualizes the world as a mixture of three primary colors, sensed by pigmented cells in the eye. This view of color vision evolved over centuries of investigation, but has now for the first time been directly demonstrated. Genes that correspond to the red, green and blue color-vision pigments have been identified by Jeremy Nathans, Darcy Thomas and David S. Hogness of Stanford University. Unexpected aspects of their findings give clues to how color vision evolved and may still be evolving.

Tests on color-blind subjects provided critical information in the identification of the pigment genes. Color blindness is caused by the absence of a normal copy of one of these genes, the scientists have demonstrated in collaboration with Thomas P. Piantanida of S.R.I. International in Menlo Park, Calif., and researchers at Roswell Park Memorial Institute in Buffalo, N.Y. Furthermore, they traced a common condition of slightly altered color vision to the presence of an abnormal pigment gene. The brains of people with this condition portray colors as if they were using a slightly different set of paints.

"Through the application of modern recombinant DNA techniques and the analysis of genetic variants, a problem as old as the human effort to understand the real world has been brought to a higher, and most satisfactory, level of understanding," says David Botstein of Massachusetts Institute of Technology in the April 11 SCIENCE in an essay accompanying the color-vision research reports.

The key to the research success was the prediction that all the eye's pigment genes would have similarities due to a common evolutionary origin. Because one single-stranded DNA will bind to another resembling its complementary strand, an isolated gene can be used to search for related DNA sequences.

Nathans and his colleagues first used a gene that had already been identified as that of the bovine visual pigment called rhodopsin. With it they located the gene for the corresponding human pigment, which is used for vision in dim light but not for color vision. Then, with this human rhodopsin gene, they were able to identify three similar DNA sequences. They found the green- and the red-pigment genes on the X chromosome and the blue-pigment gene on the chromosome known as number 7.

Analyses of the genes indicate that a common ancestral DNA segment produced three genes: one that evolved to become the rhodopsin gene, a second that became the blue-pigment gene, and a third that duplicated in more recent evolution to become the green-and red-pigment genes.

The most surprising finding is that the X chromosome of people with normal color vision often contains two or even three copies of the green-pigment gene. The frequent presence of duplicate green-pigment genes "gives evolution some material to experiment with," says Piantanida.

The variation in green-pigment gene number seems to arise from unequal exchanges of DNA between paired chromosomes. These swaps also produce the chromosomes lacking a color-vision gene, in this way creating color blindness. Sometimes the exchanges appear to occur within genes. The result is genes that are hybrids of the red-and green-pigment genes. These hybrids underlie what has been a puzzling defect in color vision.

Among U.S. Caucasian men, 8 percent have defects in their red-green color vision. The most common defect is more subtle than an inability to distinguish red from green. It is observed when the men are asked to mix red and green light to match a certain shade of yellow. Those with "anomalous trichromatism" produce a different shade than does someone with normal color vision. Nathans and his colleagues have demonstrated that these men have, instead of one normal pigment, a hybrid pigment with different light-absorption characteristics.

Now that the visual pigment genes have been identified, scientists expect to be able to obtain for the first time adequate amounts of the pigments for biochemical study.

The intriguing question remains: During fetal development, how does each visual cell determine which pigment it must produce?

Photo: Visual pigment similarities: All four human pigments and bovine rhodopsin have the same amino acid in the locations indicated by empty circles; similar amino acids at the stippled circles; and at least one "nonconservative" amino acid difference at the filled circles. --J. A. Miller