New clues to why we see red

Researchers have engineered mice to express an additional photoreceptor, a transformation that may mimic the evolution of trichromatic vision in primates, reports this week's Science. In the study, mice that express a human cone pigment sensitive to long-wavelength light can see colors that normal mice cannot.

"What this shows is that animals can develop quite sophisticated discrimination capabilities just by inserting a new class of receptors at the very front end of the visual system," said David Williams of the University of Rochester in New York, who was not involved in the study. "That's really fundamentally important in understanding how sensory systems develop."

Mice normally have two types of cone photoreceptors -- blue- and green-sensitive -- which gives them dichromatic vision. Many primates have trichromatic vision arising from the addition of a third, red-sensitive photopigment. In Old World primates, this third pigment comes from a separate gene on the X chromosome. In New World primates, the third pigment arises from a polymorphism in a single X-linked gene, which means that only females heterozygous at this locus have trichromatic vision.

Some scientists have suggested that adding a new cone pigment might be sufficient to extract new color information, "but there's been no real proof of this," said lead author Gerald Jacobs of the University of California, Santa Barbara. "The real question is: Does [new color vision] emerge immediately or does one have to then redesign the nervous system in some fashion?"

Researchers previously created a knock-in mouse in which some of the coding sequences for the normal medium-wavelength (green) pigment gene were replaced with human long-wavelength (red) cDNA. Breeding produced males and homozygous females possessing either green or red cones plus heterozygous females with a mixture of the two cone types.

To see whether the addition of this photopigment actually changed color vision in the mice, Jacobs and his co-workers trained mice to identify which of three panels was illuminated with a different color than the other two. After thousands of training trials, the researchers found that most heterozygous females could discriminate between colors that were roughly red and green, while mice with only green cones could not.

"This is really a landmark paper in sensory neuroscience," Williams told The Scientist. The results suggest that "all you need is the right sensory input and the brain will take care of the rest by itself."

"Given that the nervous system has kind of a tough job, the fact that you would just change something at the receptors and then get a whole new sense out of it is pretty amazing," said Jay Neitz of the Medical College of Wisconsin in Milwaukee, who was not involved in the work.

Not all of the heterozygous mice were equally successful at the color discrimination task, however -- two heterozygous mice failed to discriminate between red and green. "It's not entirely clear why some succeed and others don't," Jacobs said, although these two mice had relatively skewed green:red cone ratios due to random X-inactivation in the cone cells. It's possible that this led to their failure to demonstrate trichromacy, Jacobs said. Indeed, mice that succeeded on the color discrimination task had more balanced green:red ratios.

In general, the red/green color vision in mice that can distinguish between each color isn't as good as in humans, Neitz said, probably because humans have much denser arrays of cones and many more retinal ganglion cells to process the color information. "That's part of the explanation for why mice don't do as well as a primate would," Neitz said.

This limitation in the mouse visual system "makes it all the more surprising and interesting that the mouse can actually do this," Williams said.

Melissa Lee Phillips
mail@the-scientist.com

Links within this article

N. Atkinson, "How birds keep secrets in color," The Scientist, April 27, 2005.
http://www.the-scientist.com/article/display/22660/

G.H. Jacobs et al., "Emergence of Novel Color Vision in Mice Engineered to Express a Human Cone Photopigment," Science, March 23, 2007.
http://www.sciencemag.org

J.P. Roberts, "Melanopsin lights the way," The Scientist, April 26, 2004.
http://www.the-scientist.com/article/display/14629/

David Williams
http://www.cvs.rochester.edu/williamslab/p_williams.html

D.M. Hunt et al., "Molecular evolution of trichromacy in primates," Vision Research, November 1998.
http://www.the-scientist.com/pubmed/9893841

J.D. Mollon et al., "Variations of colour vision in a New World primate can be explained by polymorphism of retinal photopigments," Proceedings of the Royal Society of London Series B, September 22, 1984.
http://www.the-scientist.com/pubmed/6149558

Gerald Jacobs
http://www.psych.ucsb.edu/people/faculty/jacobs/

P.M. Smallwood et al., "Genetically engineered mice with an additional class of cone photoreceptors: implications for the evolution of color vision," PNAS, September 30, 2003.
http://www.the-scientist.com/pubmed/14500905

Jay Neitz
http://mcw.edu/cellbio/colorvision/contentpages/introduction.html