The Journal of Neuroscience, December 1, 1998, 18(23):10053-10069
Red, Green, and Red-Green Hybrid Pigments in the Human Retina:
Correlations between Deduced Protein Sequences and Psychophysically
Measured Spectral Sensitivities
Lindsay T.
Sharpe1,
Andrew
Stockman2,
Herbert
Jägle1,
Holger
Knau1,
Gert
Klausen3,
Andreas
Reitner4, and
Jeremy
Nathans5
1 Forschungsstelle für Experimentelle
Opthalmologie, Universitäts-Augenklinik Abteilung II, D-72076
Tübingen, Germany, 2 Department of Psychology,
University of California San Diego, La Jolla, California, 92093-0109, 3 Neurologische Universitätsklinik, D-79106 Freiburg
im Breisgau, Germany, 4 Universitäts Augenklinik,
1090 Vienna, Austria, and 5 Departments of Molecular
Biology and Genetics, Neuroscience, and Ophthalmology, Howard Hughes
Medical Institute, Johns Hopkins University School of Medicine,
Baltimore, Maryland 21205
To analyze the human red, green, and red-green hybrid cone
pigments in vivo, we studied 41 male dichromats, each of
whose X chromosome carries only a single visual pigment gene
(single-gene dichromats). This simplified arrangement avoids the
difficulties of complex opsin gene arrays and overlapping cone spectral
sensitivities present in trichromats and of multiple genes encoding
identical or nearly identical cone pigments in many dichromats. It thus allows for a straightforward correlation between each observer's spectral sensitivity measured at the cornea and the amino acid sequence
of his visual pigment. For each of the 41 single-gene dichromats we
determined the amino acid sequences of the X-linked cone pigment as
deduced from its gene sequence. To correlate these sequences with
spectral sensitivities in vivo, we determined the Rayleigh matches to different red/green ratios for 29 single-gene dichromats and measured psychophysically the spectral sensitivity of
the remaining green (middle wavelength) or red (long wavelength) cones
in 37 single-gene dichromats. Cone spectral sensitivity maxima obtained
from subjects with identical visual pigment amino acid sequences show
up to a ~3 nm variation from subject to subject, presumably because
of a combination of inexact (or no) corrections for variation in
preretinal absorption, variation in photopigment optical density,
optical effects within the photoreceptor, and measurement error. This
variation implies that spectral sensitivities must be averaged over
multiple subjects with the same genotype to obtain representative
values for a given pigment. The principal results of this study are
that (1) ~54% of the single-gene protanopes (and ~19% of all
protanopes) possess any one of several 5'red-3'green hybrid genes that
encode anomalous pigments and that would be predicted to produce
protanomaly if present in anomalous trichromats; (2) the alanine/serine
polymorphism at position 180 in the red pigment gene produces a
spectral shift of ~2.7 nm; (3) for each exon the set of amino acids
normally associated with the red pigment produces spectral shifts to
longer wavelengths, and the set of amino acids normally associated with
the green pigment produces spectral shifts to shorter wavelengths; and
(4) changes in exons 2, 3, 4, and 5 from green to red are associated
with average spectral shifts to long wavelengths of ~1 nm (range,
0.5 to 2.5 nm), ~3.3 nm (range, 0.5 to 7 nm), ~2.8 nm (range,
0.5 to 6 nm), and ~24.9 nm (range, 22.2-27.6 nm).
Key words:
visual pigments; cone pigments; red-green color
blindness; spectral sensitivity; human retina; protein sequences
Copyright © 1998 Society for Neuroscience 0270-6474/98/182310053-17$05.00/0
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