It's long been known that color blindness is caused, usually in men, by changes in the red and green opsin genes, the genes that enable humans to perceive color.
But a new study of randomly selected people from geographically diverse populations shows that normal variation in the red opsin gene may have been maintained by natural selection to give humans, especially women, a better perception of color.
In a study to be published in the September edition of The American Journal of Human Genetics, Brian Verrelli, formerly a postdoctoral fellow at the University of Maryland and now an assistant professor at Arizona State University, and Sarah Tishkoff, assistant professor of biology at the University of Maryland, found that one of the genes connected to color vision has maintained an unusual amount of genetic variation, possibly for millions of years of human evolutionary history.
Verrelli and Tishkoff studied the DNA of 236 men originating from various global populations from Africa, Europe, and Asia. They specifically looked at genetic variation of OPN1LW, the gene located on the X chromosome, which codes for an opsin protein that detects the red spectrum of light. This gene sometimes exchanges amino acids with a neighboring color vision gene, which codes for an opsin protein that detects the green spectrum of light.
The exchange of genetic material between the red and green color vision genes results in large amounts of genetic variation. However, this exchange can also sometimes go awry and result in color blindness. In fact, eight per cent of the world's men are color blind.
"We found 85 variants in this gene," Tishkoff said. "That's approximately three times higher than what you see at any other random gene in the human genome. Usually, it's a bad thing to have too much change in a gene, and natural selection gets rid of it. But in this case, we're seeing the reverse. Genetic exchange, or conversion, between the red and green opsin genes has created a greater number of variations than we typically see, and natural selection is acting to maintain that variation."
Those variations may have been especially important, Verrelli and Tishkoff speculate, in a time when humans were hunter-gatherers. Enhanced color perception would have allowed women, who were traditionally gatherers, to better discriminate among colored fruits, insects and background foliage.
The X Factor
The chromosomal difference between women and men is the key to why variation of the OPN1LW gene may have different results in women and men. Women have two X-chromosomes; men have only one X-chromosome and one Y-chromosome. Because this color vision gene resides on the X-chromosome, rare detrimental changes at this gene cause color-blindness in males, whereas females are likely to have at least one good copy of the gene.
However, Verrelli and Tishkoff show that color vision changes can be beneficial too. Because females can have two different versions of this gene, but men can have only one, females may be able to perceive a broader spectrum of colors in the red/orange range. "Men and women may be literally seeing the world differently," Tishkoff said.
Subtle Change Important
The findings also suggest, says Tishkoff, that geneticists may want to look at the impact subtle changes have in natural selection, especially in disease prevention. "Biophysicists have thought that if it's not a dramatic change, it doesn't matter. But we see in this study that subtle changes can make a difference."
Most human geneticists have traditionally searched for genetic variations that have large effects on color vision, such as the difference between individuals who are color-blind or not. However, says Verrelli, "Genetic variation can have very subtle effects that are difficult to measure with even the most precise equipment. For example, when looking for big differences in perception, scientists find people who distinguish between greens and reds, but may be missing the subtle variations among people who can distinguish between reds and red-oranges."
Instead of trying to look for these subtle differences in perception among people directly, Verrelli and Tishkoff looked for a genetic signature of natural selection at the red opsin gene. "By using statistical analyses of the genetic variations, we were able to determine that natural selection is responsible for the high frequency of subtle red-orange variations among human populations," Verrelli said.
New Way of Looking at Variation
Verrelli and Tishkoff used complex statistical models to analyze their data, a method they say is the wave of the future. According to Verrelli, "There are many instances when we do not have something tangible, like color vision, to measure. For instance, in looking at how people are able to stave off bacterial infection, we must rely on statistical analyses that look at changes in the genes responsible for these complex processes. These are the statistical tools that could reveal how each of us have become a unique individual as a result of natural selection, which often favors very subtle changes."
These statistical tools also enabled Verrelli and Tishkoff to distinguish between the effects of demographic history and natural selection on patterns of genetic variation in modern populations.
"The pattern we're seeing can't be easily explained by demographic history of populations. It suggests that an excess of amino acid changes are being maintained due to natural selection," Tishkoff said. "Identification of regions of the genome that show signatures of natural selection may help scientists to identify genes and molecular variants that play an important role in adaptation and evolution as well as human disease."
The study was funded by grants to Tishkoff from The Burroughs Wellcome Fund, the David and Lucile Packard Foundation and the National Science Foundation.