Encyclopedia of Color Science and Technology

2016 Edition
| Editors: Ming Ronnier Luo

Photoreceptors, Color Vision

Reference work entry
DOI: https://doi.org/10.1007/978-1-4419-8071-7_277



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.

Nathans and colleagues [1] were the first to use advances in molecular genetics to study human photopigment genes, involving the technique of recombinant DNA (deoxyribonucleic acid). Visual pigments are the light-absorbing molecules that mediate vision with absorption maxima at approximately 420 nm (S-), 530 nm (M-), and 560 nm (L-wavelength sensitive pigment). Structurally, they consist of opsin, transmembrane heptahelical proteins of a single polypeptide chain composed of either 364 (M- and L-cone pigment genes) or 348 (S-cone pigment gene) amino acids bound to a chromophore, 11-cis retinal. Photon absorption by the pigment molecules initiates visual excitation by causing an 11-cis-to-all-trans isomerization of the chromophore. The binding socket site of the chromophore in both the cone and rod opsins is located in helix 7 (Fig. 1).
Photoreceptors, Color Vision, Fig. 1

Arrangement of visual pigments in a cone photoreceptor. The infolding membrane of the cone outer segment is packed with photopigment molecules. The molecule consists of seven α-helices which span the membrane of the cell surrounding the chromophore, 11-cis-retinal. The NH2 (N) terminus is extracellular, whereas the COOH (C) terminus is intracellular. Shown in the bottom right is the sequence of amino acids that make up this heptahelical molecule. Comparison between the L- and M-cone pigments shows the amino acids that are equal (white circles) and different (dark circles). The substitutions at positions 180, 277, and 285 are believed to contribute most of the spectral difference between the M- and L-cone pigments (Adapted from Sharpe [2] and Nathans [1])

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 [3]. The exact amino acid sequence of opsin “spectrally tunes” the pigment to a specific wavelength [4, 5].

The genes encoding the S-cone pigments reside alone as a single copy on the q-arm (long arm) of chromosome 7 [6]. The genes encoding the L and M-cone pigments reside on the q-arm of the X-chromosome organized in a tandem array [1] of up to six exons (coding regions of DNA) separated by relatively long introns (noncoding regions of DNA) (Fig. 3). The S-cone pigment shows only 43 ± 1 % analogy in the amino acid sequence in comparison with either the M- or L-cone photopigments. In contrast, the M- and L-cone pigment genes are 96 % homologous, differing only in 15 amino acids [2]. The approximate 30 nm spectral difference between these two visual pigments must be attributable to substitutions at these particular amino acid positions. These differences are confined to exons 2–5. The largest shifts in λmax are produced by substitutions at two key sites within exon 5: amino acid positions 277 (~7 nm) and 285 (~14 nm) (Fig. 1). These result in spectral shifts of 15–25 nm, the exact value depending on sequences in exons 2–4. Substitutions at the sites in exons 2–4 produce much smaller shifts of less than ~4 nm and may be responsible for the subtle differences underlying anomalous and normal color vision. Both in vitro [1, 4] and in vivo [7] methods used to investigate protein sequence variation and spectral sensitivity are in close agreement. These methods have also shown that amino acid substitutions in exon 2 contribute very little to spectral tuning (0.0–0.7 nm) [4, 7]. More recently, it has been speculated that the amino acid differences in exon 2 are involved in controlling the optical density of the L- and M-cone photopigments [8]. The optical density depends on the concentration of the photopigment in the cone outer segment, the length of the cone outer segment, and also the extinction coefficient which describes the probability of a photon being absorbed [9]. Changes in the effective optical density of cones cause a broadening of the spectral sensitivity curve away from the absorption peak of the pigment (Fig. 2). If two genes that differ only in their exon 2 sequences are expressed, the resulting differences in the optical density of the photopigments may account for some residual color vision discrimination [8].
Photoreceptors, Color Vision, Fig. 2

Theoretical spectral sensitivity curves for the L-cone sensitive pigment. Changes in the optical density of the cone pigment may occur from amino acid substitutions in exon 2 altering the stability of the molecule or the efficiency with which it absorbs light. For wavelengths near the peak, the optical density qualitatively mimics the difference produced by a spectral shift

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 [1].

Figure 3 shows an example of how the formation of hybrid genes produces pigments with abnormal spectral sensitivity. The spectral sensitivity of the photopigment will depend on which L- or M-cone gene the crossover originated from [12]. Visual pigment gene arrays for people with normal color vision have an L gene in the most upstream or leftmost position and M genes downstream or to the right of the L gene. Color normals usually have only one copy of the L-cone gene, multiple copies of M, and possibly a number of hybrids [2]. There is good evidence from studies of gene expression in the retina and from studies involving phenotype-genotype relationships [13] that only the first two genes are expressed and have a significant role in color vision. While color normals have an L- and an M-cone gene occupying the two most proximal positions of the array from the locus control region (LCR), anomalous trichromats must have a hybrid gene positioned in either the first or second position. Deutan color vision arises if a hybrid gene encoding an M-cone gene sensitive pigment occupies second position. Protanomalous observers are missing normal L-sensitive photopigments, and color vision arises from two M-cone genes that differ subtly in spectral absorption properties [5]. The M- and L-cone opsin gene can take many forms giving hybrid variants and polymorphisms, and it is this variability underlying the huge differences in red/green color vision observed within the population. Even among people with normal color vision, differences in color matching behavior are associated with individual differences in L-cone pigments [11].
Photoreceptors, Color Vision, Fig. 3

Schematic of the tandem array of L-and M-cones on the q-arm of the X chromosome. (a) The LCR (locus control region) can activate only one of the promoter regions just upstream of a gene. The promoters are regulatory units upstream of the transcription site and regulate the rate of DNA transcription into RNA and hence the amount of opsin gene expression (for DNA, upstream is to the left and downstream to the right). The opsin-coding sequences are divided into exons (black bars). The intron sequences (gaps) are silent or noncoding and usually believed to have no apparent function. (b) Schematic of unequal intragenic crossover that would produce hybrid genes (Adapted from Neitz and Neitz [11])

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 [14]. Three mutations have been established causing amino acid substitutions that perturb the structure or stability of the S-cone photopigment [6], 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.

Future Directions

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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© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Optometry and Visual ScienceCity University LondonLondonUK