Photoreceptors, Color Vision
It is the molecular structure of the genes that encode the human cone photopigments and their expression in photoreceptor cells. Alterations in these genes have consequences on the spectral sensitivity of the cone photopigments which in turn affect how the color-normal and color-deficient individual see the world.
Normal trichromats can match any color by combining three suitably chosen primaries in appropriate proportions. Those that differ from normal trichromats with respect to the proportions of the primaries may either require that the three primaries be present in unusual quantities or may only need two primaries. The first type of variation is known as anomalous trichromatism, and it is assumed that it arises when three classes of cones are present, one of which contains a photopigment with an anomalous absorption spectrum. The second type of variation is known as dichromatism and occurs if only two of the three classes of cones are present. The type of deficiency involved causes differences in the chromatic sensitivity that can be identified easily by psychophysical tests of color vision. Different classes of phenotypes can be identified in this way and correspond to L-, M-, or S-cone deficiency. On the other hand genotype refers to characteristics of an individual’s genes. Studies of the empirical relation between a genetic code and an expressed phenotype have led to improved understanding in the physiological mechanisms underlying many individual differences in color vision.
The precise wavelength maxima (λmax) of a given pigment will be determined by the amino acid sequence of the opsin and the interaction of specific amino acids with retinal . The exact amino acid sequence of opsin “spectrally tunes” the pigment to a specific wavelength [4, 5].
The close similarities between the L- and M-cone sensitive pigment genes suggest evolution from a single gene. Comparison of amino acid sequences suggests that S-cones and rod receptors arose first from a common ancestral receptor. From comparisons with contemporary New World monkeys, which only have two photopigments, it is thought that a long-wavelength gene duplicated and diverged to originate the red and green photopigments, at the time when Old World monkeys (trichromatic) separated from New World monkeys [1, 10]. The location of the genes for the M- and L-cone pigments on the X-chromosome can account for the larger number of (red/green) color-deficient men compared to women, as men have only one X-chromosome. The head-to-tail arrangement of the L- and M-cone genes on the X-chromosome is susceptible to mispairing during meiosis, leading to unequal crossing over between gene arrays. If the crossover occurs between genes, this will result in the deletion of a gene from one chromosome and its addition to the other, whereas a crossover within a gene will lead to the production of a hybrid gene that combines regions of the L and M genes into a single gene. Such hybrid genes are thought to be the genetic basis responsible for the majority of color vision defects .
By contrast, the S-cone opsin gene sequence is nearly invariant in the human population; however, further phenotype-genotype studies are yet to be performed to prove this. Intragenic crossover, the mechanism that permits the frequent manifestation of anomaly in protan and deutan defects, has no analogy in tritan defects. No polymorphisms causing shifts in λmax have been reported so far, and only one substitution was found in the coding sequences and exon-intron junctions . Three mutations have been established causing amino acid substitutions that perturb the structure or stability of the S-cone photopigment , therefore strongly affecting the performance of the S-cone photoreceptors. Further complications lie in the fact that any small variations in λmax would be difficult to dissociate from individual variations in macular pigment and lens density measured psychophysically or in vivo.
An important issue in color vision is how spectral differences between two photopigments actually translate to color discrimination performance and how other retinal and cortical factors (such as individual variability in postreceptoral signal gain that precedes the formation of color-opponent channels) act upon the photopigment differences and influence discrimination. To distinguish anomalous trichromacy and dichromacy it is not enough to look at λmax differences. There are other factors such as optical density and differences in postreceptoral amplification of cone signals that may explain the observed phenotype. When color vision depends on subtle differences between the two pigments, as in color vision defects, relating genotype- phenotype requires consideration of genetic polymorphisms that might affect optical density as well as those that shift λmax. It has been suggested that a separation greater than ~20 nm would be sufficient to account for normal color vision. This implies that the majority of normal trichromats can in principle have hybrid genes encoding their visual pigments providing the λmax between L- and M- cones remains greater than 20 nm.
Changes in λmax, photoreceptor optical densities, and/or postreceptoral amplification of cone signals appear to be the most important parameters that affect our red-green chromatic sensitivity. A complete description of the relative importance of each of these parameters in determining a subject’s color discrimination performance remains a difficult task. The use of information derived from genetic analysis of pigment genes together with psychophysical data on chromatic sensitivity and modeling work could be used to understand and account for the large variability in chromatic discrimination and color matches observed in both normal and color-deficient observers.
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