Eye evolution

Main interests

Metazoan eye is a fascinating organ to be used for evolutionary studies. Early morphological studies have suggested that eye has evolved multiple times during the course of evolution. In contrast, more recent genetic data indicate a central role of Pax6 in eye development in most of the animals. In addition, other genes acting dowstream of Pax6 in the regulatory cascade (e.g. Six, Eya or Dach genes) are also highly evolutionarily conserved. However, most of our current knowledge is based on experimental work done in vertebrates and Drosophila melanogaster. To gain deeper insight into eye and photoreceptor evolution, we use various vertebrate and invertebrate model systems.


Assembly of the cnidarian camera-type eye from vertebrate-like components.
(Kozmik Z, Ruzickova J, Jonasova K, Matsumoto Y, Vopalensky P, Kozmikova I, Strnad H, Kawamura S, Piatigorsky J, Paces V, Vlcek C., Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):8989-93.)

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 camera-type 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.

Two scenarios for the use of ciliary phototransduction and melanogenic pathway in eye evolutionary history.
A simplified view of the two evolutionary scenarios is compatible with the data in the present work. The use of similar genetic components in vertebrate and cubozoan eyes is either due to common ancestry (A) or independent parallel recruitments in cnidarian and vertebrate lineages (B). The c-opsins and Go/r-opsins arose by duplication and diversification of an ancestral opsin in the early metazoans (27). In the schemes, only the visual (i.e., the eye-specific) PRCs and opsins are considered. Different shading of pigment granules indicates possible distinct chemical composition. CBA, cnidarian–bilaterian ancestor; UBA, urbilaterian ancestor.

Eye evolution: common use and independent recruitment of genetic components
(Vopalensky P and Kozmik Z, Philos Trans R Soc Lond B Biol Sci. 2009 Oct 12;364(1531):2819-32)

Animal eyes can vary in complexity ranging from a single photoreceptor cell shaded by a pigment cell to elaborate arrays of these basic units, which allow image formation in compound eyes of insects or camera-type eyes of vertebrates. The evolution of the eye requires involvement of several distinct components-photoreceptors, screening pigment and genes orchestrating their proper temporal and spatial organization. Analysis of particular genetic and biochemical components shows that many evolutionary processes have participated in eye evolution. Multiple examples of co-option of crystallins, Galpha protein subunits and screening pigments contrast with the conserved role of opsins and a set of transcription factors governing eye development in distantly related animal phyla. The direct regulation of essential photoreceptor genes by these factors suggests that this regulatory relationship might have been already established in the ancestral photoreceptor cell.

Dual role of transcription factors in regulation of both eye development and differentiation genes.
The box on the left-hand side represents the sum of largely unknown developmental genes regulated by corresponding transcription factors based on functional data. The letters represent different animals (V – vertebrates, A – ascidians, D - Drosophila, C – cnidarians, M – mollusks, P - planarians). The arrows on the right-hand side represent a direct influence of a given factor on differentiation set of genes proved by biochemical methods (DNA-binding assay, ChIP, transgenesis, luciferase assays etc.) The green arrows indicate the ancestral interaction proposed by the “bipartite” model. The red arrow highlights the proposed role of Otx in the regulation of ancestral phototransduction genes. Co-option of certain transcription factor to a new role is indicated by dashed line. We propose that the transcription factors were independently co-opted for regulation of genes governing eye development in different species and these downstream genes may vary among species. Please note that cross-regulatory interactions of transcription factor are not considered in this scheme for simplicity.

´Paxcentric´ view of eye evolution.
(Kozmik, 2005, Current Opinion in Genetics and Development 15, 430-438)

Pax transcription factors represent regulatory proteins with unusually broad spectrum of target sequences due to interaction of independent DNA binding domains or cooperation between the domains. They are thus capable of coordinately regulating large number of genes organized into networks or developmental programs. Separate, yet interdependent biological program(s) can be regulated by PD and HD, respectively. We propose that two independent DNA binding domains within a single Pax transcription factor have been co-opted for two essential features of the proto-eye: production of a dark pigment (´pigmentation´ program, PD driven) and production of a photopigment (´opsin´ program, HD driven). The two programs being driven by two independent DNA binding domains within a single transcription factor became unseparable.

The ´Paxcentric´ (bipartite, PD-HD) model
proposes an evolutionarily conserved function for paired domain in pigmentation (and morphogenesis) and for homeodomain in opsin gene regulation, respectively. The fascinating feature of the proposed model is that the morphological unity found in the eye, a photoreceptor linked to the shading pigment, is mirrored on the molecular level, by uniting two indepednent DNA-binding domains in one regulatory protein: Pax.

Pax-Six-Eya-Dach network during amphioxus development: conservation in vitro but context-specificity in vivo
(Kozmik et al., 2007, Dev Biol.;306(1):143-59)

The Drosophila retinal determination gene network occurs in animals generally as a Pax-Six-Eyes absent-Dachshund network (PSEDN). For amphioxus, we describe the complete network of nine PSEDN genes, four of which - AmphiSix1/2, AmphiSix4/5, AmphSix3/6, and AmphiEya - are characterized here for the first time. For amphioxus, in vitro interactions among the genes and proteins of the network resemble those of other animals, except for the absence of Dach-Eya binding. Amphioxus PSEDN genes are expressed in highly stage-and tissue-specific patterns (sometimes conspicuously correlated with the local intensity of cell proliferation) in the gastrular organizer, notochord, somites, anterior central nervous system, peripheral nervous system, pharyngeal endoderm, and the likely homolog of the vertebrate adenohypophysis. In this last tissue, the anterior region expresses all three amphioxus Six genes and is a zone of active cell proliferation, while the posterior region expresses only AmphiPax6 and is non-proliferative. In sum, the topologies of animal PSEDNs, although considerably more variable than originally proposed, are conserved enough to be recognizable over a wide spectrum of developing tissues; this conservation may reflect indispensable involvement of PSEDNs during the critically important early phases of embryology (e.g. in the control of mitosis, apoptosis, and cell/tissue motility).

A diagrammatic summary of the developmental expression of amphioxus genes described here
(AmphiSix41/2, AmphiSix3/6, AmphiSix4/5, and AmphiEya) combined with previously published information on AmphiPax1/2, AmphiPax2/5/8, AmphiPax3/7, AmphiPax6, and AmphiDach in the context of (A) mid gastrula (6 h), (B) early neurula (14 h), (C) late neurula (18h), and (D) early larva (48 h). Lower case letters indicate structures referred to in the text, as follows: a, dorsal region of invaginating mesoderm; b, pharyngeal endoderm; c, rostral (possible olfactory) ectoderm; d, anterior end of neural plate; e, cells associated with the first organ of Hesse; f, somite; g, notochord; h, Hatschek’s left diverticulum/preoral pit; i, cerebral vesicle; j, anterior spinal cord; k, probably type I sensory neurons; l, dorsal pharyngeal endoderm; m, lateral pharyngeal endoderm; n, thickened pharyngeal endoderm in gill slit region; o, intestinal endoderm just within anus. A color-coded key for the genes is at the left center. Parallel stripes of color on a structure signify the simultaneous expression of genes there and are not intended to indicate dorsoventral regionalization. Because of the anatomical complexity of the pharyngeal region, the following information is not shown in the diagram: AmphiSix4/5, AmphiDach, and AmphiPax2/5/8 expression in the endostyle; early AmphiPax1/9 and late AmphiSix1/2 expression in the club-shaped gland; AmphiPax2/5/8 and AmhiPax3/7 expression in the rudiment of Hatschek’s nephridium; and AmphiSix3/6, AmphiEya, and AmphiPax3/7 expression in the rudiment of the rostral coelom. Another feature that cannot be indicated here is AmphiPax3/7 expression along either edge of the neural plate in the early neurula.