Animal eyes are morphologically diverse. Their assembly, however, always relies on the same basic principle, i.e., photoreceptors located in the vicinity of dark shielding pigment. Cnidaria as the likely sister group to the Bilateria are the earliest branching phylum with a well developed visual system. Here, we show that cameratype eyes of the cubozoan jellyfish, Tripedalia cystophora, use genetic building blocks typical of vertebrate eyes, namely, a ciliary phototransduction cascade and melanogenic pathway. Our findings indicative of parallelism provide an insight into eye evolution. Combined, the available data favor the possibility that vertebrate and cubozoan eyes arose by independent recruitment of orthologous genes during evolution.T he assembly of diverse animal eyes requires two fundamental building blocks, photoreceptors and dark shielding pigment. The function of photoreceptors is to convert light (stream of photons) into intracellular signaling. The photoreceptor cells (PRCs) are classified into two distinct types: rhabdomeric, characteristic of vision in invertebrate eyes; and ciliary, characteristic of vision in vertebrate eyes (1). In both ciliary and rhabdomeric PRCs, the seven-transmembrane receptor (opsin) associates with retinal to constitute a functional photosensitive pigment. Each photoreceptor type uses a separate phototransduction cascade. Rhabdomeric photoreceptors employ r-opsins and a phospholipase C cascade, whereas ciliary photoreceptors use c-opsins and a phosphodiesterase (PDE) cascade (2, 3). In general, the dark pigment reduces photon scatter and orients the direction optimally sensitive to light. The biochemical nature of the dark pigment appears more diverse than the phototransduction cascades used by the PRCs. Vertebrate eyes use melanin as their exclusive dark pigment. However, among invertebrates, pterins constitute the eye pigment in the polychaete Platynereis dumerilii (4), pterins and ommochromes are accumulated in eyes of Drosophila (5), and melanin is found rarely such as in the inverse cup-like eyes of the planarian, Dugesia (6).Cnidaria, the likely sister group to the Bilateria, constitute the earliest branching phylum containing a well developed visual system. For example, Cubozoa (known as ''box jellyfish'') have camera-type eyes with cornea, lens, and retina; unexpectedly, the cubozoan retina has ciliated PRCs that are typical for vertebrate eyes (7-9). Cubomedusae are active swimmers that are able to make directional changes in response to visual stimuli (10). The cubozoan jellyfish, Tripedalia cystophora (Fig. 1A), has four sensory structures called rhopalia that are equally spaced around the bell. In addition to two camera-type lens containing eyes at right angles to one another, each rhopalium has two pit-shaped and two slit-shaped pigment cup eyes (Fig. 1B). Thus, with six eyes located on each rhopalium, Tripedalia has 24 eyes altogether. Because the visual fields of individual eyes of the rhopalium partly overlap, Tripedalia (like other Cubomedusae) has an al...