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The human retina depicted below uses molecules
of rhodopsin to detect light and allow for vision.
How did this sense evolve? Opsins are G protein
coupled receptors which are known in organisms as primitive as bacteria.
The ancestors of vertebrates possessed a number of opsins
expressed in neural tissue and other tissues which were involved in a
number of responses to light other than vision.
The vertebrate eye evolved from neural tissue which expressed opsins. A duplication in the
red opsin gene in the ancestor of
OPSINS AND VISION
Light detection is an ancient sense, known in every major group of living organisms including bacteria. Distinguishing between different wavelengths of light (i.e. color vision), is even demonstrated in the wavelength-dependent phototactic responses of halobacteria (Nathans, 1999). Most organisms rely on opsin proteins for the detection of light. The rhodopsin group is one of the largest family of genes within the G protein coupled receptor superfamily (which is the largest gene family in eukaryotes). Members of this family have been modified to perceive biogenic amines (adrenaline, dopamine, histamine, and serotonin), short peptides, proteins (LH, FSH), nucleosides, nucleotides, lipids, eicosanoids, and light (Fredriksson, 2003). The opsins are G-coupled protein receptors in which the 7 transmembrane regions form a pocket into which a chromophore molecule (retinaldehyde; the aldehyde derivative of vitamin A) can covalently link (OMIM).
Bacteriorhodopsin is homologous to eukaryotic GPCRs, although the order of the transmembrane helices is different (Pardo, 1992). Homologs of bacteriorhodopsin are known in primitive eukaryotes (Aravind, 2003). Opsins in archaea also bind retinal (although in trans, rather than in cis) and function in phototaxis and in light-induced ion transport. Archaeal-like rhodopsins are found in diverse archaea and eubacteria. Halobacterium produces four separate opsins. The fungus Neurospora produces a homolog of archaeal opsins (Bieske, 1999; Beja, 2000). The two types of opsin differ in a number of characteristics but are similar in their molecular architecture. The alga Chlamydomonas expresses two rhodopsins of the archeal-type (type I) which mediate its phototaxis. (Suzuki, 2003). The alga Volvox also possesses rhodopsin (Andreeva, 2001).
Retinal (vitamin A aldehyde) is used in more than three hundred light-reacting proteins in prokaryotes and eukaryotes. Type I rhodopsins are known in archaea, algae, and fungi where their functions include light-responsive ion transporters and phototaxis mediators (Spudich, 2000). Archaea are pictured below.
Type II opsins are only known in animals. Insects express an opsin similar to those of vertebrates in their brains where it apparently functions in non-visual tasks (Velarde, 2005).
While animals in general rely heavily on vision, there are some exceptions. Even in blind animals, however, opsin expression may be retained. It is thought that the ancestors of the Mexican blind cavefish, Astynax fasciatus, were separated from other populations about a million years ago. During development, the photoreceptors in the eye begin to develop but later degenerate before becoming fully formed. The eyes briefly produce opsin during their development (Parry, 2003). Blind cavefish and crayfish can express opsin genes (David-Gray, 1999). Although the eyes of blind mole rats are degenerate, they do express a long wave opsin which is thought to regulate circadian rhythms (the only function known for the eyes). The eyes are only .6 mm in diameter and these are the most atrophied eyes known in mammals. The visual areas of the brains of blind mole rats have been reduced 87-93% (David-Gray, 1999).
A number of vertebrates have adapted their opsins to perceive UV light with a small number of changes in the amino acid sequence of the short wave opsin gene (typically five or fewer) (Yokoyama, 2000). UV light is abundant enough at depths of 100 meters to function in visual perception and could represent 18% of the light available. Many teleosts have 3-4 color opsins including one which is sensitive to UV light (Losey, 1999). There are 5 subfamilies of opsins: LWS (which includes human red and green opsins), RH1 (which includes human rhodopsin), RH2, SWS1 (which includes human blue), and SWS2 (Hisatomi, 2002).
How did the vertebrate eye evolve? Opsins and the ability to detect light evolved long before vertebrates. Vertebrates possess a number of opsins and some are expressed in tissues other than the eye, such as neural tissue. Even those which are expressed in the eye may function in responses to light other than vision. It seems that the ancestors of vertebrates possessed neural tissue which could respond to light and that some of this tissue improved its perception of light to allow for vision.
The optic vesicles form as part of the forebrain.
|This is evident in embryonic chick pictured below.||A pig embryo is depicted below.|
Many of the proteins which function in vision seem to have originated from ancestral gene family members as a result of duplications of large sections of DNA. These genes include opsins, G proteins, phosphodiesterases, cyclic nucleotide-gated channels, G-protein coupled receptor kinases, arrestins and recoverins. Very ancient duplications, for example, gave rise to rhodopsin, long wave opsin, short wate opsin, RRH (peropsin), and RGR (Nordstrom, 2004).
Three opsins are known in tunicates and as many as six in lancelets. Lampreys possess an opsin which belongs to the RH1 subfamily (Hisatomi, 2002). Humans have at least 8 opsins in their genome, which is probably similar to the number of ancestral gnathostomes. A tunicate larva is pictured below.
Of the human opsins, rhodopsin, blue short wave opsin, red long wave opsin, and green long wave opsin are more similar to each other than to the remaining human opsins, such as perospin, encephalopsin, melanopsin, and RGR-opsin. Of the latter group, peropsin and RGR-opsin are the most similar although tracing the evolution of these opsins is more difficult given that they seem to have accumulated changes more rapidly than observed in the visual opsins (Nordstrom, 2004).
Vertebrates not only possess photoreceptor molecules in their rods and cones, they can exist in other retinal cells, the deep brain, the pineal complex, and the skin. (Kojima, 1999). In non-mammals, the iris and melanocytes of the skin can mediate responses to light (Blackshaw, 1999). All non-mammals have photoreceptors in both their deep brains and their pineal glands, at least in embryonic development. In halibut, the photoreceptors of the pineal gland rather than those of the retina, are capable of photoreception before hatching (Forsell, 1997). The pineal gland of halibut expresses short and middle wavelength opsins during its embryonic and adult life and larval production may be particularly important since it occurs before the retina is functional (Forsell, 2002).
Birds possess different types of photoreceptor cells (rods, double cones, and four types of single cone) and five types of visual opsin. Some paleognathus birds (with only two known from tinamiformes and emus) have fewer opsin genes than most neognathus birds (the group to which the majority of birds belong) (Hart, 2001). Eels possess two rod opsin genes whose relative expression changes after sexual maturity (Zhang, 2000). Fish may express red cone opsins in their pineal gland during development and continue to express low levels in adulthood. Exo-rhodopsin and VA opsin may also be expressed in the pineal gland (Kojima, 1999).
Most mammals have dichromatic vision because of short wave (blue) and long wave (red) cone pigments. The mammalian blue pigments belong to the same subfamily as chicken violet pigments; chicken blue and goldfish blue pigments arose from separate duplications of rhodopsin. The chicken green pigment also arose from a separate duplication of rhodopsin and is not related to the green opsins of catarrhine primates (OMIM).
Melanopsin is more closely related to rhodopsin of invertebrates than other vertebrate opsins. Human opsins belong to three separate groups: human RGR (homologous to squid retinochrome), peropsin, and the rhdopsin subgroup. The rhodopsin subgroup includes a variety of opsins including human encephalopsin (the first to diverge from the rest of the group), VA opsin and parapinopsin (in fish), human rhodopsin, human red and green opsins (related to pinopsin in chickens), and blue opsin (related to goldfish UV opsin).
GPR21 is a member of the rhodopsin family expressed in the brain (more specifically, the caudate and putamen).
(Other GPRs of unknown function are also expressed in the brain—GPR55 is expressed in the caudate and the putamen, GPR26 is expressed in all the brain regions of mice).
RGR—Retinal G-coupled Receptor
This receptor represents one of the earliest branches from the vertebrate opsin family which would produce photoreceptors. It is a light sensitive molecule (which converts trans-retinal to its cis conformation) expressed in the retina in cells adjacent to photoreceptor cells (retinal layer with photoreceptors is on the right in the image below).
In tunicates, three visual proteins, RGR (retinal G protein coupled receptor from which rhodopsin may have been derived), CRALBP (cellular retinaldehyde-binding protein which is important in the isomerizaiton of photopigments necessary for the perception of light), and BCO/RPE65 (required for mammalian vision) are expressed throughout the brain and visceral ganglion, indicating that the central nervous system in general participates in light detection in addition to the specialized eyespot (Tsuda, 2003). In mammals, the retinal pigment epithelium expresses RGR-opsin and peropsin but no photosensory function of this tissue is known (Peirson, 2004).
Cone opsins evolved in the vertebrate lineage after the separation of protostome and deuterostome lineages (Nathans, 1986b). The ancestral condition for vertebrates seems to have been 3 retinal opsins (rhodoposin, a color opsin with maximum absorption <500 nm, and a color opsin with maximum absorption >500 nm) in addition to extraretinal opsins. Ancestral mammals possessed this repertoire of retinal opsins while the opsin duplications in birds produced four cone opsins (including one opsin derived from a duplicate rhodopsin), rhodopsin, and pinospin) (Nathans, 1999).
VERTEBRAL ANCIENT OPSIN (VA OPSIN)
This opsin is known from the deep brains of lampreys and teleost fish, it is not yet known from tetrapods. It is also present in retinal cells other than the photoreceptors for vision (i.e. it is present in horizontal and amacrine cells; those on the left and middle layers above). The gene can produce alternate transcripts (Moutsaki, 2000; Halford, 2001;
This opsin is known from the pineal glands of reptiles and birds and the deep brain of toads. The pineal gland is photoreceptive in chickens and affects the production of melatonin (Debreceni, 1998;.Halford, 2001;
P opsin is an opsin specific to the pineal gland in lampreys, reptiles, and birds (Yokoyama, 1997).
This opsin evolved from the rhodopsin of teleosts and is present in the pineal glands of fish (Mano, 1999).
This opsin is present in the pineal gland of catfish (Halford, 2001;.
This opsin is present in the deep brain, melanocytes, horizontal cells, and iris of toads. In mice and primates (including ourselves) it is present in the ganglion and amacrine cells of the retina (layers on the left in the image below). It is known that mammals need their eyes for circadian rhythms (“biological clocks”) but they do not need their rods and cones, the photoreceptor cells involved in vision. The distribution of the cells which have melanopsin in the retina is similar to the distribution of cells which project from the retina to the suprachiasmatic nuclei of the hypothalamus which controls circadian rhythms (Provencio, 2000; Halford, 2001) . Retinal ganglion cells respond to light and project to those parts of the brain which control pupil diameter and circadian rhythms (Peirson, 2004).
Melanopsin is about as closely related to other human opsins as are invertebrate opsins
Deep brain opsins of amphibians seem
to control gonadal responses to light (Kojima,
1999). The homolog of melanopsin
in teleost fish is expressed in the horizontal
cells of the retina (
Melanopsin is structurally and functionally more similar to those of invertebrates to those of vertebrate rods and cones. Most vertebrates possess two genes for melanopsins, Opn4x and Opn4m. Given that all mammals lack Opn4x, including monotremes and marsupials, it appears that an ancestral melanopsin gene was lost in early mammals, perhaps as during adaptation to nocturnal lifestyles (Hankins, 2008).
This opsin is present in the retinal epithelia of the mouse and humans. It is about as closely related to other human opsins as are invertebrate opsins (Blackshaw, 1999). Six opsin genes are known in lancets, including members of the peropsin and encephalopsin groups (Kovanagi, 2002).
This opsin is expressed in both the retina and brain of humans. In the brain, it is expressed in areas which are involved in non-visual light responses (such as specific regions of the hypothalamus) in addition to other areas (regions of the cerebral cortex, cerebellar Purkinje cells, striatum, thalamus, and even the spinal cord). The expression of non-visual opsins in mammalian retinas is not unexpected since it has been demonstrated that some of the responses to light in mammals (such as circadian rhythms and the regulation of melatonin production) requires the presence of eyes but not the presence rods and cones. Panopsin is also expressed in the human liver and testes. (Halford, 2001; Blackshaw, 1999).
The panopsin gene seems to be an ancient gene, resulting from a duplication in ancestral opsin genes near the base of this family tree in animals. The CHML gene is actually located in the first intron of the panopsin gene (Halford, 2001;
Neuropsin is expressed in the mammalian eye, CNS, and testis. It is expressed both in the neural retina and in the RPE (Tarttelin, 2003).
Non-ocular photoreception is not known in mammals (Tarttelin, 2003).
Additional opsins are present in teleosts which resulted from a duplication of rod-opsins in ancestral teleosts. Extra-retinal opsins are responsible for circadian rhythms, behavior, pupil size regulation, and body coloration in fish (Philp, 2000). In vertebrates, it seems that tissues outside the nervous system have circadian rhythms which are not established (but may be modified) by the central nervous system. Zebrafish possess a multiple tissue opsin which is expressed in both neural and non-neural tissues and in cell lines which possess an entrainable clock (Moutsaki, 2003).
The vertebrate retina (such as that of the pig embryo above), possesses opsin molecules which allow the vision in black and white in addition to the perception of color. Rhodopsin is the pigment of rods which registers images as dark and light (rather than color). Rhodopsin works best in dim light. It is important for the morphogenesis of photoreceptors and mutations result in retinitis pigmentosa. The rhodopsin sequences of therian mammals lack 5 amino acids which found in other vertebrates, apparently as a result of an ancestral deletion (Hunt, 2003).
OPSINS FOR COLOR
SHORT WAVE PIGMENTS
The gene for the blue cone pigment is located
on chromosome 7q31 and mutations in this gene, causing tritanopia, are not sex-linked. Most mammals are dichromatic because they possess
two cone opsins: one for short wavelengths of
light (such as blue) and another for longer wavelengths (red and green).
LONG (red) AND MIDDLE (green) WAVE PIGMENTS
Most mammals are dichromatic; that is they cannot distinguish between red and green. As a result, deer hunters can wear orange jackets and it doesn’t matter if a bullfighter waves a red or green flag in front of an angry bull. Ancestral primates were dichromatic and nocturnal. A single Middle/Long wave opsin which responds to both red and green is the ancestral condition for primates and is also the condition in bats, tree shrews and most prosimians (Heesy, 2001). Red and green pigments are closely homologous, differing by about 12 amino acids. Differences in the amino acids at positions 180, 230, and 285 are responsible for the differences in maximal light absorption of the red and green opsins. (Nathans, 1986a; 1986b).
All male new world monkeys are dichromat but in some species, the females are trichromat. Polymorphisms
of the red/green opsin gene are known in a number
A duplication of a single ancestral red gene
in the ancestors of
New mutations in these opsin genes continue to generate variation. In humans, variants of the cone opsins can have slightly different wavelengths of maximal absorption (Merbs, 1992). In one study, a polymorphism in the red pigment gene caused variation in color perception; 62% of the subjects had a serine at residue 180 of the protein and 38% had alanine here (Winderickx, 1992).
The L opsin and M opsin genes are located in tandem on the X chromosome. While most people have one red opsin gene on each X chromosome, others have from two to four. Some people have one copy of the green opsin gene but multiple copies (from two to seven) are more common. It seems that multiple copies can be expressed, increasing an individual’s ability to make intermediate color matches. Gene duplications on the X chromosome have produced multiple long and middle wave pigments. Multiple copies of red or green pigments are more closely related to each other, having diverged more recently. One study of two green genes indicated that they differed by only one nucleotide. (Nathans, 1986a; 1986b)
Most non-primate mammals and more primitive primates (prosimians and New World Monkeys) have one opsin for long wavelengths of light. Old world monkeys and apes have two genes resulting from gene duplication: red and green. Some people have multiple copies of red (up to four) and green opsins (up to seven) (Neitz, 1995).