Ask a Neuroscientist: Human Tetrachromacy

Our latest question comes from Gabby, a photography student in New York City, who asks: 

I very recently stumbled upon some of the articles that have been posted online about tetrachromacy, trying to maybe find some answers for the things that I see, and I’m really curious about it because I believe that I may be one of the few women that has the genetic make up for it. Everything that I’ve found thus far has really accurately described the way that I see and perceive color and I’m kind of excited to possibly, finally get some answers for what is happening.  I never really realized that I saw anything differently than anyone else, but over the last couple of years, my friends and family have started to point out (and poke fun at) that fact that I was trying to describe colors that they weren’t seeing at all. … I’m wondering if there is anyway I can find out more about what I see, and gather a greater understanding of it or possibly help others / researchers to gather more information. 

Hey Gabby, although strong tetrachromacy is fairly rare, it seems completely possible to me that you could have it. To understand how it might happen and how we would be able to tell if that’s what’s going on, let’s start with a quick review of how the average person sees color. Among the many cell types that make up the retina at the back of your eyeball are a type of light-sensing cell called cone cells. Each of these cone-shaped photoreceptor cells contains many copies of a single variety of light-absorbing pigment. For most people, there are 3 types of pigment proteins, or opsins, each of which is expressed in a single class of cone cells.

Each of these opsins has a different set of wavelengths of light that it prefers to absorb. The long-wavelength opsin (L-opsin) absorbs and is most excited by 564 nm wavelengths, which is in the range of red light. The short-wavelength opsin (S-opsin) responds best to blue light around 420 nm, and the medium-wavelength opsin (M-opsin) prefers green light around 534 nm.

Preferred absorbance of each opsin: S, M, and L are the cone opsins. Rhodopsin (R) is present only in rod cells, and is not relevant for color. Note: computer screens cannot display violet. Adapted from Wikimedia Commons, 1 and 2.

Preferred absorbance of each opsin: S, M, and L are the cone opsins. Rhodopsin (R) is present only in rod cells, and is not relevant for color. Note: computer screens cannot display violet. Adapted from Wikimedia Commons, 1 and 2.

When we see color in the world around us, it’s generally a mixture of various wavelengths of light. If you have mostly red wavelengths hitting your eye, then you’ll have a larger proportion of red cone cells (those that contain L-opsin) being excited compared to green or blue cone cells. If you have an equal amount of red and green, then your visual system might interpret the combined excitation of red and green cone cells as yellow. Like the RGB sliders you’d see on a color picker on your computer, your visual system puts together different quantities of your three primary colors to represent the color you’re seeing. It’s actually a little more complicated because you have more red cones and fewer blue cones, but that’s the basic idea.

An RGB color slider lets you choose the intensity of each color channel to make the color on the right (source).

An RGB color slider lets you choose the intensity of each color channel to make the color on the right (source).

Keep in mind that your “primary colors” are defined by the wavelengths your opsins are most responsive to. This means that a tetrachromat with 4 different opsins can have 4 primary colors instead of 3 – that is, each color they see can be broken down into the relative excitations of four cone types.

This brings us to the first of three major things you need in order to be considered a true, strong tetrachromat.

  1. You need 4 cone classes with substantially different color preferences.
  2. Your brain should be able to distinguish between the activity of all 4 types of cone cells.
  3. This ability to distinguish 4 primary colors should be reflected in your behavior.

How do you get 4 cone types?

Sorry fellas, your chances of being a tetrachromat are pretty much nil. This is one battle of the sexes in which women win out. The genes for the M- and L-opsins, which are almost identical (the proteins they encode differ only in 15 amino acids), are located on the X chromosome. Since males have only one X, they have only one copy of each gene. If something goes wrong with one of those copies (a common occurrence – the genes are so similar and close together on the chromosome that they sometimes get mixed up), a male can end up with color-blindness. The most common form is deuteranopia, a loss of the green-sensing opsin, followed by protanopia, loss of function of the red-sensing opsin. If, however, the protein is mutated so that it responds to different wavelengths but remains functional overall, the male can be considered an anomalous trichromat. That is, he still has three primary colors, but one of them is different than the usual.

The daughter of a male with an altered L-opsin (an anomalous trichromat with protanomaly) and a woman with normal trichromacy will receive one X chromosome from her mother and the anomalous opsin-containing X chromosome from her father. She has two copies of the normal S-opsin and two of the normal M-opsin, but also one of the L-opsin and one of the new opsin – let’s call it L2-opsin.

Tortoiseshell cat displaying X-inactivation (Source).

Tortoiseshell cat displaying X-inactivation (Source).

Women are like cats. More specifically, women are like tortoiseshell cats. Although we have two X chromosomes, we don’t really need twice as many of those proteins as males have. To cut down the dosage of these proteins, we basically turn off one of the X chromosomes; this is called X-inactivation. What’s cool is that this inactivation happens randomly to either the maternal or paternal X chromosome at a certain stage in development, which tends to lead to a patchwork pattern of paternal or maternal x chromosome expression. In a tortoiseshell cat, each of the coat colors is encoded by one of the X chromosomes, and you can see which one is still turned on in any given patch based on which color the fur is. Similarly, in the retina, X-inactivation means that you can actually get patches that contain only L-opsin or L2-opsin. When the daughter’s cone cell “decides” to be an L-opsin kind of cone, half the time it will actually be an L2 type of cone depending on which X was active in its precursor cell.

Can the brain tell which cone is which?

Okay, now you’ve got 4 types of cones. How can your brain handle that? Wouldn’t it be wired for 3 since that’s what the majority of the species has? It seems this isn’t the case. The mammalian brain’s plasticity, its ability to change or adapt its behavior and connections based on its experience, is very strong.

Most New World monkeys (gibbons, squirrel monkeys, all the ones with the extremely useful-looking prehensile tails) are dichromats – unless you happen to be a female who gets two slightly different opsins from her parents. Sound familiar? In this case, though, we’re actually going to look at male squirrel monkeys, because of a really neat experiment published in Nature in 2009.

Dalton the male squirrel monkey was treated with S-opsin. The picture on the left was altered to simulate what Dalton would probably have seen before the treatment, while the picture on the right is what he would have seen as a newly minted trichromat. Source: Neitz lab.

Dalton the male squirrel monkey was treated with S-opsin. The picture on the left was altered to simulate what Dalton would probably have seen before the treatment, while the picture on the right is what he would have seen as a newly minted trichromat. Source: Neitz lab.

Mancuso et al. took adult male squirrel monkeys, which have only the equivalent of our S- and M-opsins, and used gene therapy to introduce a human L-opsin into the retina1. Around 15-36% of cells that had previously been M-opsin cones also took up this new opsin gene and started expressing it, shifting their preference to a longer wavelength (it’s unclear whether they were still expressing M-opsin, but there was a shift). Within less than a year, these monkeys, which could previously only tell apart blue and yellow, could now discriminate between red and green as well (check out this interactive demo to see how cones would react to light in each monkey). We don’t yet know exactly what is happening with the neurons in the visual cortex*, but given that the time course of behavioral change so closely followed the time course of opsin expression, the authors suggested that there wasn’t any extensive rewiring in the retina. Rather, “gaining a new dimension of color vision becomes a simple matter of splitting the preexisting blue-yellow pathway into two systems, one for blue-yellow and a second for red-green color vision”2 .

[*Editor’s Note: For a discussion on designing an experiment to test for differences in brain function between human tetrachromats, those with colorblindness, and common trichromats, see Erica Seigneur blog post.]

Basically, once the brain learns that the two pathways are now giving it different information, it can make use of this. It’s astonishing, but this study and a similar one done in mice3 suggest that the brain can handle describing the world with extra colors – all you need is the extra cone type to give you that input.

Can humans actually perceive more colors and behave accordingly?

There haven’t been very many studies looking at tetrachromacy in humans because color perception is such a subjective experience that it’s difficult to find people who know their color vision is different (color-blind males often go years without realizing it).  A couple of researchers at Cambridge and Newcastle universities, however, figured out how to exploit the genetics of tetrachromats to find them. Remember how our example tetrachromat woman got one slightly weird X chromosome from her father? Well, she now has a 50% chance of passing that X on to her sons, who would then be anomalous trichromats like their grandfather. By testing boys who were anomalous trichromats, they found mothers who were potential tetrachromats.

Over the course of two studies and 15 years, Jordan et al. tested many women like these, and found a few whose behavior matched what you might expect of a tetrachromat5,6. For example, “Mrs. M,” a tetrachromat they found in the first study, described a rainbow as being made up of 10 distinct colors instead of the 7 most of us see4.

The basic task used in these studies was the Rayleigh matching task. Participants were shown yellow light of a single wavelength, which would excite their M- and L-cones but not their S-cones. Then they were given control of a red and green light of specified wavelength, and asked to adjust the intensity of each until the mixture looked the same as the yellow light. For a trichromat, this is easy, since there are many such combinations. For a tetrachromat with an extra opsin between M and L, we might guess this would be impossible because their mental representation of this “yellow” includes a color besides just red and green.

Cone excitation ratios are drawn as the height of the cone’s excitation spectrum at the point of the given wavelengths. A normal trichromat will have his/her cones excited in the same ratio by yellow light of this wavelength and this particular mixture of red and green light. Even with different pairs of red and green wavelengths, you could adjust the intensity of each to excite the red and green cone cells in the desired amount and ratio. A tetrachromat, however, will find the mixture to be missing a color component.  Source: S.Katta

Cone excitation ratios are drawn as the height of the cone’s excitation spectrum at the point of the given wavelengths. A normal trichromat will have his/her cones excited in the same ratio by yellow light of this wavelength and this particular mixture of red and green light. Even with different pairs of red and green wavelengths, you could adjust the intensity of each to excite the red and green cone cells in the desired amount and ratio. A tetrachromat, however, will find the mixture to be missing a color component.
Source: S.Katta

As it turns out, 8 women in the first study5 refused all possible matches, commenting that they “want[ed] to be able to add more orange to the mixture, not red” or that the resulting color was “the wrong kind of orange”, which suggests that our hypothesis is correct.

In the second study6, published in 2010, the researchers created tasks that didn’t require such a subjective judgment, but were based on the same idea.  Now the participants simply had to pick out which of three color patches was a mixture of red and green rather than a single wavelength of yellow. One woman picked these out extremely quickly and with 100% accuracy. Next, the researchers altered some of their color perception tests so that only someone with an M-opsin and an intermediate opsin would get them right. Just like their anomalous trichromat sons, some of these women were able to distinguish colors that normal trichromats could not. Because they had all 4 opsins instead of 3, they could also distinguish normal trichromat colors that their sons could not. When the researchers actually looked at the opsin genes, they found that these women did in fact have an extra hybrid opsin, made partly of M and partly of L, that was predicted to have a maximum light response between the peaks for the M- and L-opsins.

The curious thing, however, was that not all women that fulfilled the criterion of having an intermediate opsin were able to better distinguish colors. Only one woman of the 31 potential tetrachromats behaved like a tetrachromat on all behavioral tests. Although 12% of all women might actually have 4 different opsins, very few can make use of this diversity, and it’s not completely clear why. In some cases, it might be that the new opsin is not sufficiently different from the old ones that it actually provides new information. The brain might not see its signal as being much different from the original opsin, and might just lump the new opsin together with the normal ones. Or perhaps it depends on how much of each type of cone you have in your retina or how spotty the coverage is.

The Bottom Line

In any case, Gabby, if you can see and distinguish more colors than the normal trichromat, it seems like you got really lucky. And as for getting involved with tetrachromacy research, your best bet might be to contact the Cambridge/Newcastle research team (although they seem to prefer folks living in the Newcastle area of England). Nevertheless, they might be able to point you to a US based group, if one exists. Their website also contains some useful tips for how to figure out whether you are a potential tetrachromat (e.g. are your maternal male relatives slightly color blind?)

References:

  1. Mancuso, K. et al. Gene therapy for red–green colour blindness in adult primates. Nature 461, 784–787 (2009).
  2. Neitz lab website.
  3. Jacobs, G. H., Williams, G. A., Cahill, H. & Nathans, J. Emergence of Novel Color Vision in Mice Engineered to Express a Human Cone Photopigment. Science 315, 1723–1725 (2007).
  4. 4. Looking for Madam Tetrachromat By Glenn Zorpette. Red Herring magazine, 1 November 2000.
  5. 5. Jordan, G. & Mollon, J. D. A study of women heterozygous for colour deficiencies. Vision Research 33, 1495–1508 (1993).
  6. 6. Jordan, G., Deeb, S. S., Bosten, J. M. & Mollon, J. D. The dimensionality of color vision in carriers of anomalous trichromacy. J Vis 10, 12 (2010).