human tetrachromate mutant reported

From: Eugene.Leitl@lrz.uni-muenchen.de
Date: Tue Nov 28 2000 - 13:34:18 MST


(((ferreted out by Alan Grimes <alangrimes@starpower.net>
   tetrachromate primate mutants are not new, but human ones, and
   possibly functional, wow)))

http://www.redherring.com/mag/issue86/mag-mutant-86.html

Looking for Madam Tetrachromat
Do mutant females walk among us?

By Glenn Zorpette
>From the December 04, 2000 issue

"Oh, everyone knows my color vision is different," chuckles Mrs. M, a
57-year-old English social worker. "People will think things match,
but I can see they don't." What you wouldn't give to see the world
through her deep blue-gray eyes, if only for five minutes.

Preliminary evidence gathered at Cambridge University in 1993 suggests
that this woman is a tetrachromat, perhaps the most remarkable human
mutant ever identified. Most of us have color vision based on three
channels; a tetrachromat has four.

The theoretical possibility of this secret sorority -- genetics
dictates that tetrachromats would all be female -- has intrigued
scientists since it was broached in 1948. Now two scientists, working
separately, plan to search systematically for tetrachromats to
determine once and for all whether they exist and whether they see
more colors than the rest of us do. The scientists are building on a
raft of recent findings about the biology of color vision.

The breakthroughs come just in time. "Computers, color monitors, and
the World Wide Web have made having color blindness a much bigger deal
than it ever was before," says Jay Neitz, a molecular biologist who
studies color vision at the Medical College of Wisconsin in
Milwaukee. Color-blind individuals, he explains, often lose their way
while navigating the Web's thicket of color cues and
codes. "Color-blind people complain miserably about the Web because
they can't get the color code," Dr. Neitz says. (Just try surfing on a
monochrome monitor.)

Most people are trichromats, with retinas having three kinds of color
sensors, called cone photopigments -- those for red, green, and
blue. The 8 percent of men who are color-blind typically have the cone
photopigment for blue but are either missing one of the other colors,
or the men have them, in effect, for two very slightly different reds
or greens. A tetrachromat would have a fourth cone photopigment, for a
color between red and green.

Besides the philosophical interest in learning something new about
perception, the brain, and the evolution of our species, finding a
tetrachromat would also offer a practical reward. It would prove that
the human nervous system can adapt to new capabilities. Flexibility
matters greatly in a number of scenarios envisaged for gene therapy.
For example, if someone with four kinds of color photopigments cannot
see more colors than others, it would imply that the human nervous
system cannot easily take advantage of genetic interventions.

For years now, scientists have known that some fraction of women have
four different cone photopigments in their retinas. The question still
remains, however, whether any of these females have the neural
circuitry that enables them to enjoy a different -- surely richer --
visual experience than the common run of humanity sees. "If we could
identify these tetrachromats, it would speak directly to the ability
of the brain to organize itself to take advantage of novel stimuli,"
says Dr. Neitz. "It would make us a lot more optimistic about doing a
gene therapy for color blindness."

There have been very few attempts to find Madam Tetrachromat. The one
that turned up Mrs. M in England, in 1993, was led by Gabriele Jordan,
then at Cambridge University and now at the University of
Newcastle. She tested the color perception of 14 women who each had at
least one son with a specific type of color blindness. She looked at
those women because genetics implies that the mothers of color-blind
boys may have genetic peculiarities of their own. Among that somewhat
peculiar group of women, one could expect to find the odd
tetrachromat.

It's almost as if the supersense these women enjoy comes at the
expense of the men in their families. "I'm just sorry I've robbed my
son of one of his color waves," Mrs. M says.

Dr. Jordan reports that of the fourteen test subjects in her study,
two showed "exactly" the behavior that would be expected of
tetrachromats. "It was very strong evidence for tetrachromacy," she
adds. The apparent tetrachromats were Mrs. M, who was identified in
the study as cDA1, and another candidate, cDA7.

Dr. Jordan set up an experiment in which subjects tried to determine
whether a pair of colored lights matched. They used joysticks to blend
two different wavelengths as they pleased. The resulting hues lay
outside the spectrum of the blue photoreceptor, rendering it nearly
useless, so that normal trichromats would have the use of only their
red and green photoreceptors. Having hit upon a color, the subjects
would then try to reproduce it by mixing two other wavelengths.
Because the tetrachromats had the use of only two receptors, they
found a whole slew of mixes that produced a matching color.

However, any tetrachromat should have been able to use three receptors
in this color space, and therefore make a single, precise match. In
the experiment, cDA1 and cDA7 performed pretty much as a tetrachromat
would be expected to.

Nevertheless, Dr. Jordan declines to say that she has finally found a
tetrachromat, partly because her testing is still a work in
progress. The vast majority of us have no idea what tetrachromacy
would be like. Anyone who had the supersense wouldn't know she did,
let alone be able to describe it. After all, it is an exercise in
futility for trichromats to try to explain their visual experience to
color-blind people.

Dr. Neitz and Dr. Jordan each plan a more definitive search for
tetrachromats. Dr. Neitz plans to take advantage of the fuller
understanding of the underlying genetics of color vision. His will be
the first experiment that will use genetic techniques to identify
women with four different color photopigments.

What will he be looking for? Let's start with the basics. The genes
for the red and green photopigments are adjacent to each other on the
X chromosome; strangely, blue is way off by itself on another
chromosome. Women, of course, have two X chromosomes and therefore two
sets of red and green photopigment genes. Men have only one X, so they
have just one shot at getting the red and green photopigment genes
right.

Unfortunately for men, it turns out that those genes are prone to a
kind of mutation that occurs when eggs are formed in a female
embryo. When the eggs are created, the X chromosomes from the maternal
grandmother and grandfather mix with each other in random places to
make the egg's brand-new X chromosome. Because the genes for the red
and green photopigments are right next to each other, those genes
sometimes mix. That's perfectly normal. But every once in a while,
the mixing occurs in a lopsided way, and the result, 30 years later,
could very well be a man who has to check with his wife every time he
dresses.

A lopsided mix can have three outcomes: (1) the egg in the embryo has
an X chromosome that's missing either a red or a green photopigment
gene, (2) the X chromosome has two slightly different red photopigment
genes, or (3) the X chromosome has two slightly different green
photopigment genes. In any of these cases, if that egg gets fertilized
and becomes a male, the man will get that X chromosome and be
color-blind.

Here it gets interesting. Suppose a woman inherits one X chromosome
with two slightly different green photopigment genes. And let's say
her other X chromosome has the normal complement of red and green
photopigment genes. Because of a well-known biological phenomenon
called X inactivation -- which causes some cells to rely on one X
chromosome and others to rely on the other -- that woman's retinas
would have four different types of photopigments: blue, red, green,
and the slightly shifted green. (It would also be possible, through a
different genetic sequence, to produce blue, green, red, and a shifted
red.) X inactivation is only possible in women, so there has never
been, and probably never will be, a male tetrachromat.

True tetrachromacy would require a few other characteristics in
addition to retinas with four different photopigment receptors. For
instance, there would have to be four neural channels to convey to the
brain the sensory inputs from the four receptors, and the brain's
visual cortex would have to be able to handle this four-channel
system. If a woman were born with four types of photopigments, would
her brain wire itself to take advantage of them? No one knows for
sure, but some experts strongly suspect it would. "Yes, definitely,"
says Jeremy Nathans, a pioneer in color-vision research at Johns
Hopkins University School of Medicine. One reason to think so is the
brain's great plasticity in other respects. People with special
skills -- musicians, bilinguals, deaf people who learn sign language
-- often show characteristic brain patterns.

Dr. Nathans also believes, however, that for full-blown tetrachromacy,
the fourth photopigment must not have a peak in sensitivity that is
too close to the peaks of either the red or the green
photopigments. That's the rub, as far as he's concerned -- he suspects
that most female tetrachromats would have only mildly superior color
vision, because the genetics indicates that the fourth photopigment
would almost always be very close to either the red or the green.
Every now and then, however, an oddball photopigment might appear,
well separated from both red and green. "The genetics do not rule it
out," Dr. Nathans explains. "It would be a rare event. But who's to
say it hasn't happened? There are a lot of people out there."

That idea finds support in the recent discoveries about the genetics
of color vision, many made by Dr. Neitz's group. Those findings have
shown that the genetics underlying color vision are surprisingly
variable, even within the narrow range regarded as normal. "The
variety in photopigment genes in people with normal color vision is
enormous," Dr. Neitz reports. "It's enormous."

Would there be any practical advantages to tetrachromacy? Dr. Jordan
notes that a mother could more easily spot when her children were pale
or flushed, and therefore ill. Mrs. M reports that she has always been
able to match even subtle colors from memory -- buying a bag, for
example, to match shoes she hasn't laid eyes on for months. And
computers, color monitors, and the Internet raise a whole raft of
possibilities. Just as someone with normal three-color vision surfs
rings around a dichromat on the Internet, a tetrachromat, looking at a
special computer screen based on four primary colors rather than the
standard three, could theoretically dump data into her head faster
than the rest of us.

If Dr. Neitz or Dr. Jordan finally finds Madam Tetrachromat, the
discovery will confirm that the human nervous system can handle
four-channel color vision. And that confirmation would raise the
possibility that, within a couple of decades, gene therapy will make
tetrachromacy just another option that wealthy parents could check off
on the list when they are designing their daughters.

It won't be possible with male children -- not for quite some time,
anyway. So as long as we're on this flight of fancy, let's take one
more short hop: a few decades from now, men and women will still be
seeing the world differently. But the expression might not be merely
figurative any more.

ADDITIONAL RESOURCES
Free book chapter on color vision.

Q & A on the biology of human color vision.

Web site for Jay Neitz's laboratory on color vision at the Medical
College of Wisconsin. Includes images showing how the color blind
would see certain scenes and objects.

Explanation of the genetics behind color-vision deficiencies.



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