1 Opsin genes, cone photopigments, color vision, and color blindness Lindsay T. Sharpe, Andrew Stockman, Herbert Jägle, and Jeremy Nathans In this chapter, we introduce the molecular struc- ture of the genes encoding the human cone photopig- ments and their expression in photoreceptor cells. We also consider the consequences that alterations in those genes have on the spectral sensitivity of the pho- topigments, the cone photoreceptor mosaic, and the perceptual worlds of the color normal and color blind individuals who possess them. Throughout, we high- light areas in which our knowledge is still incomplete. Trichromacy. Human color vision is trichromatic; this has three consequences. First, as was recognized in the eighteenth century (e.g., Le Blon, 1722; see Bir- ren, 1963, 1980), but only formally postulated (Grass- man, 1853) and verified (Maxwell, 1855, 1860) in the nineteenth century, the number of independent vari- ables in color vision is three. That is, all colors can be matched by just three parameters: either by the three primaries of additive light mixture – typically, violet, green, and red – or by the three primaries of subtrac- tive pigment mixture – typically, cyan, yellow, and magenta. Second, as intimated by Palmer (1777, 1786; see also Voigt, 1781; Walls, 1956; Mollon, 1997), defini- tively stated by Young (1802, 1807), and revived by Helmholtz (1852), trichromacy is not a physical prop- erty of light but a physiological limitation of the eye: All color perceptions are determined by just three physiological response systems. Third, as pointed out by Maxwell (1855) and applied by König and Dieterici (1886), a linear trans- form must exist between the tristimulus color match- ing properties of the eye, as established by the three primaries of additive light mixture, and the spectral sensitivities of the three physiological systems medi- ating the matches (see Chapter 2). The three physiological response systems are uni- versally acknowledged to be the three types of retinal photoreceptor cell, each containing a different photo- pigment: the short (S)-, middle (M)-, and long (L)- wave sensitive cones. 1 These have distinct, spectral sensitivities (Fig. 1.1A) or absorption spectra (Fig. 1.1B), which define the probability of photon capture as a function of wavelength. The absorbance spectra of the S-, M-, and L-cone photopigments overlap con- siderably, but have their wavelengths of maximum absorbance (λ max ) in different parts of the visible spectrum: ca. 420, 530, and 558 nm, respectively. When estimated in vivo, the λ max ’s are shifted to longer wavelengths (ca. 440, 545, and 565 nm, res- pectively) by the transmission properties of the inter- vening ocular media: the yellowish crystalline lens and the macular pigment of the eye (see Chapter 2). The individual cone photopigments are blind to the wavelength of capture; they signal only the rate at 1 The fourth type of photoreceptor cell, the rods, contain rhodopsin as their photopigment. They are by far the most prevalent in the human retina, constituting more than 95% of all photoreceptor cells. However, they do not contribute to color vision, except under limited, twilight conditions (see section on rod monochromacy). Under most daylight conditions, where we enjoy color vision, the rod photore- ceptor response is saturated by excessive light stimulation.