View source for UCSCGeneAnnotation:hg18-358

[[Category:Genome Annotation]]
Canonical gene details [http://genome-test.cse.ucsc.edu/cgi-bin/hgGene?org=Human&hgg_gene=uc003emt.1 RHO uc003emt.1]<BR>
<B>Description:</B> rhodopsin<BR><B>RefSeq Summary (NM_000539):</B> Retinitis pigmentosa is an inherited progressive disease which is a major cause of blindness in western communities. It can be inherited as an autosomal dominant, autosomal recessive, or X-linked recessive disorder. In the autosomal dominant form,which comprises about 25% of total cases, approximately 30% of families have mutations in the gene encoding the rod photoreceptor-specific protein rhodopsin. This is the transmembrane protein which, when photoexcited, initiates the visual transduction cascade. Defects in this gene are also one of the causes of congenital stationary night blindness.   <BR>
(description snapshot 4 September 2008)<BR>
<B>Alternate Gene Symbols:</B> NM_000539, NP_000530, OPN2, OPSD_HUMAN, P08100, Q16414, Q2M249<BR>

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''created: [[User:Tomemerald|tom]] 09:14, 4 September 2008 (PDT)''&nbsp;'''uc003emt.1'''

The rhodopsin gene encodes the much-studied 7-transmembrane protein responsible for vertebrate dim light (grayscale) vision, with expression limited to retinal rod cells. Its 11-cis-retinal cofactor detects incoming photons but with wavelength sensitivity shifted from its inherent ultraviolet adsorption to a peak around 500 nm by a dozen tuning residues, not all in direct physical proximity. [http://www.pnas.org/content/early/2008/09/02/0802426105.abstract Evolution of RHO spectral tuning] has been the subject of a Sept 2008 review.

There is profound potential for nomenclatural confusion because 'rhodopsin' is used indiscriminately for highly non-orthologous (melanopsin-class opsins) genes in fruit fly and other protostomes. Worse, the entire subdivision of GPCR (heterotrimeric G protein coupled receptors) is often called rhodopsin although many members have no connection whatsoever to photoreception. Consequently key word searches are all but useless at GenBank and PubMed for retrieving rod-specific opsin information. 

Deuterostome imaging opsins such as RHO arose during the Cambrian subsequent to the divergences of echinoderms, urochordates and cephalochordates but prior to lamprey ancestor. However ciliary opsins themselves (which include RHO) arose in pre-Bilatera and persisted to the present day in non-imaging roles in both protostomes and deuterostomes. [http://genomewiki.ucsc.edu/index.php/Opsin_evolution:_key_critters_(cnidaria) Imaging mono-color vision in cnidaria] uses a ciliary opsin that is homologous to rhodopsin but more closely related in properties to encephalopsin and TMT opsin.

A common misconception is that rod vision arose first, with color vision a later elaboration. This is factually backwards as seen from lamprey which has a full complement of color vision opsins. There is near-universal agreement that the gene tree for imaging opsins is best described by [http://genomewiki.ucsc.edu/index.php/Opsin_evolution:_LWS_PhyloSNPs serial tandem expansions of LWS (long wave sensitive), with RHO the last to emerge.] Vertebrate imaging opsins themselves arose from ciliary opsin genes found today in pineal photoreceptors and their antecedents. 

Even though the circumscribed era of ciliary opsin gene expansion matches perfectly, the overall opsin gene tree topology conflicts with theories of one or two rounds of whole genome polyploidization prior to lamprey divergence. If 1R or 2R occured, it was irrelevent to opsin gene family expansion (notably to the emergence of RHO) because the history here appears entirely tandem duplications followed by local inversions and later translocations to other chromosomes.

RHO was named in the 1870s by Kuehne but it took over a century to determine the first structure of bovine rhodopsin, a great advamce in the overall understanding of GPCR signaling proteins. Hundreds of other human genes can be modeled accurately via this structure, though not to the level of detail needed for pharmacological work. While peak optical adsorptions in rhodopsin and other imaging opsins can be accurately predicted just from primary sequence, only 3D structure can suggest the chemical basis.

RHO orthologs have been sequenced for a great many species. However for many purposes it is preferable to use a phylogenetically dispersed representative sub-sample. For example, chondrichthyes furnish an excellent close-in outgroup to over-sampled teleost fish. A curated collection of RHO (and all other opsins) is available in the [http://genomewiki.ucsc.edu/index.php/Opsin_evolution:_update_blog comparative genomics section of genomeWiki.]

Rhodopsin directly interacts with several other proteins during the visual cycle; notably a particular alpha subunit of heterotrimeric G protein called rod transducin (GNAT1 gene product) initiates the downstream signalling cascade. Here a short cytoplasmic peptide at the boundary of the last transmembrane segment of rhodopsin binds to the carboxy terminal region of transducin, probably explaining sequence conservation of rhodopsin in this region. Cone opsins utilize GNAT2, another of the 16 alpha subunit genes in humans. 

Rhodopsin is unusual in having a dedicated transducin because most alpha subunits must service a wide variety of different GPCR proteins. This situation -- components with different duplication histories, lineage-specific gains and losses, non 1:1 correspondence to opsins, and multiple use across different signaling systems -- highlights the nuances of addressing Darwin's question of how many times vision evolved.