In bright light, then, when the cones are active, how do we perceive colors?
Nathans' ambitious plan to isolate the genes that coded for the three color receptor proteins depended on Wald's view that the genes all evolved from the same primordial ancestor.
The only visual receptor protein that had been studied with any intensity at that time was bovine rhodopsinfrom the rod cells of cows' eyes. Scientists had purified bovine rhodopsin and deduced the sequence of a fragment of the DNA that coded for it. Nathans used this information to construct a lurea single strand of DNAwith which he fished out the complete gene for bovine rhodopsin from a sea of bovine DNA.
Next he used part of this bovine gene as a lure to catch the gene for human rhodopsin from the jumble of DNA in a human cell. This took less than a year "because the genes for human and bovine rhodopsin are virtually identical, despite an evolutionary distance of 200 million years between cattle and humans," Nathans says.
Finding the human genes for the color receptors proved more challenging, however, since these genes are less closely related to the gene for rhodopsin.
Nathans began to sift through DNA from his own cells. "I figured I'd be an unlimited source of DNA as long as I kept eating," he says. Eventually he fished out some pieces of DNA that belonged to three different genes, each of them clearly related to the rhodopsin gene.
"This coincidencethree genes, three types of conesdidn't escape our notice," he said. Furthermore, two of these genes were on the X chromosome"exactly what one would expect," says Nathans, "since defects in red and green color vision are X-linked."
By experimenting with prisms as early as 1672, Isaac Newton made the fundamental discovery that ordinary "white" light is really a mixture of lights of many different wavelengths, as seen in a rainbow.
Objects appear to be a particular color because they reflect some wavelengths more than others. A red apple is red because it reflects rays from the red end of the spectrum and absorbs rays from the blue end. A blueberry, on the other hand, reflects the blue end of the spectrum and absorbs the red.
Thinking about Newton's discovery in 1802, the physician Thomas Young, who later helped decipher the hieroglyphics of the Rosetta Stone, concluded that the retina could not possibly have a different receptor for each of these wavelengths, which span the entire continuum of colors from violet to red. Instead, he proposed that colors were perceived by a three-color code.
As artists knew well, any color of the spectrum (except white) could be matched by judicious mixing of just three colors of paint. Young suggested that this was not an intrinsic property of light, but arose from the combined activity of three different "particles" in the retina, each sensitive to different wavelengths.
We now know that color vision actually depends on the interaction of three types of conesone especially sensitive to red light, another to green light, and a third to blue light. In 1964, George Wald and Paul Brown at Harvard and Edward MacNichol and William Marks at Johns Hopkins showed that each human cone cell absorbs light in only one of these three sectors of the spectrum.
Wald went on to propose that the receptor proteins in all these cones were built on the same plan as rhodopsin. Each protein uses retinal, a derivative of vitamin A, to absorb light; and each tunes the retinal to absorb a different range of wavelengths.
Wald believed that the three receptor proteins in cones probably evolved from the same primordial geneand so did rhodopsin. They were all "variations on a central theme," Wald wrote in his Nobel lecture.
This evolutionary message was music to Nathans' ears. It meant that if the gene encoding only one receptor protein could be located, the genes encoding the other receptor proteins could be found by the similarity of the sequence of bases in their DNA.
"I realized while reading Wald's lecture," says Nathans, "that Wald had laid out the whole problem of the genetic basis of color vision, and that this problem was now solvable, completely solvable, by molecular genetic methods." Wald had taken the problem as far as he could, Nathans pointed out. "But lacking these molecular methods, he couldn't go any further."
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