View source for Opsin evolution: RGR phyloSNPs

== Introduction to RGR Opsin Evolution ==

=== A Curated Set of 54 RGR Opsins ===

The collection of RGR opsin reference sequences is greatly expanded below to 54 species of vertebrates from the more limited yet phylogenetically representative set found in the opsin classifier. This expanded set brings much needed branch length to detailed studies of evolutionary change such as reduced alphabets at given residues, phyloSNPs, alternative splice forms, and gene loss in marsupials.

It has not proven possible to date to find an ortholog of RGR in any species diverging prior to lamprey (other than perhaps tunicate). tBlastn searches of the new amphioxus genome yields nothing, as does blastn searches of the trace archives. Similarly, no closely related homologs can be found in earlier deuterostomes and protostomes, even though neuropsins and peropsins are readily traced back further. Since RGR is an ancient gene family (based on intronation and weak blastp matches) -- rather than derived in Bilateran times from a nearest paralog -- RGR genes must have been retained along the stem but not in most terminal leaves.
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=== Comparative genomics of RGR at E/DRY ===

The comparative genomics of RGR illustrates the danger of generalizing from phylogenetic under-sampling (just studying humans and mice): with deeper sampling of 56 species, it emerges that the E/DRY motif -- conserved across all classes of opsins (including generic GPCR) and critical to maintaining non-signalling state -- has become GRY in all boreoeutheran mammals (it's ERY in afrotheres and xenarthrans and DRY from platypus back to shark and even tunicate divergence, and DRY consistently in neuropsins and peropsins). 

In other words, after several trillion years of branch length conservation as charged amino acid, a radical amino acid substitution has taken hold in laurasiatheres and euarchontoglires -- to a glycine with its minimal inert side chain. And in this subclade of placental mammals, this glycine has been conserved without exception for over two billion years of branch length, not consistent with gain of a different selective pressure. 

Given the importance of this motif for maintaining the non-signalling state, this suggests a major change in functional properties of RGR opsins within boreoeutheres. Yet there are no obvious differences in ciliary opsin imaging vision between or retinal pigment epithelia of elephants and humans. And how does [http://www.jbc.org/cgi/content/abstract/283/28/19730 11-cis-retinal replenishment] work in marsupial? (Opossum genome has lost due to a chromosomal rearrangement; the gene is also absent from wallaby assembly and brushtail transcripts.) No obvious change took place in cone or rod opsins either at the transition form D to E to G.

We might ask whether any correlated residue change took place in another residue, either adjacent in the linear sequence or adjacent after the 3D structure is considered. To do this, the phylogenetic depth must be increased to the maximum possible today (50 vertebrate genomes) and every residue scored for clade-congruent changes. 

It emerges that no contemporaneous coevolutionary changes accompanied the D to G transition. The bulk of such changes occured on the 75 myr stem between the platypus divergence node and placental node. These cannot be further resolved because marsupials lost RGR. The other cluster of clade-coherent events occurs on the stem dividing ray-finned fish and tetrapods. (Here fish are not assumed primitive -- they simply share the ancestral value with earlier diverging cartilaginous fish.)

 RGR_homSap  RWPYGSDGCQAHGFQGFVTALASICSSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_panTro  RWPYGSDGCQAHGFQGFVTALASICSSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_gorGor  RWPYGSDGCQAHGFQGFVTALASICSSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_ponPyg  RWPYGSDGCQAHGFQGFVTALASICSSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_nomLeu  RWPYGSDGCQAHGFQGFVTALASICSSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_macMul  RWPYGSDGCQAHGFQGFVTALASICSSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_papHam  RWPYGSDGCQAHGFQGFVTALASICSSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_calJac  RWPYGSDGCQIHGFQGFVTALASICGSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_tarSyr  RWPYGLDGCQAHGFQGFVTALASIGGSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_otoGar  RWPYGSGGCQAHGFQGFTTALASICGSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_micMur  RWPYGSGGCQAHGFQGFTTALASICGSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_tupBel  RWPYGSDGCKVHGFQGFATALASISGSAAIAW<font color="magenta">GRY</font>HQYCT  
 RGR_musMus  RWPHGSEGCQVHGFQGFATALASICGSAAVAW<font color="magenta">GRY</font>HHYCT  
 RGR_ratNor  RWPHGSEGCRVHGFQGFATALASICGSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_cavPor  HWP-GSGHCQALGFQGFTTALASISGTAALSW<font color="magenta">GRH</font>QQCCT  
 RGR_dipOrd  HWPYGLEGCQAHGFQGFVTALASISGSAAIAW<font color="magenta">GRC</font>HHHCT  
 RGR_speTri  RWPYGSDGCQAHGFQGFVTALSSICGSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_oryCun  RWPYGSDGCQAHGFQGFATALASICGSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_ochPri  RWPYGSDGCQAHGFQGFATALASICGSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_bosTau  RWPYGSEGCQAHGFQGFVTALASICSSAAVAW<font color="magenta">GRY</font>HHFCT  
 RGR_susScr  RWPYGSEGCQAHGFQGFATALASICSSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_turTru  RWPYGSDGCQAHGFQGFVTALASICSSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_equCab  RWPYGSEGCQAHGFQGFVTALASICSSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_felCat  RWPYGSNGCQAHGFQGFVTALASICSSAAIAW<font color="magenta">GRY</font>HHYCS  
 RGR_eriEur  RWPYGSDGCQAHGFQGFVMALASICSSAAIAW<font color="magenta">GRY</font>HHHCT  
 RGR_myoLuc  RWPYGSGGCQAHGFQGFAAALASICGSAAVAW<font color="magenta">GRY</font>HHYCT  
 RGR_pteVam  RWPFGPDGCQAHGFQGFATALASICSSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_canFam  RWPYGPDGCQAHGFQGFATALASICSSAALAW<font color="magenta">GRY</font>HHYCT  
 RGR_sorAra  RWPFGPDGCQAHGFQGFATALASICSSAAIAW<font color="magenta">GRY</font>HHYCT  
 RGR_loxAfr  RWPYGSDGCQAHGFQGFVTALASICSCAAIAW<font color="blue">ERY</font>HHYCT  
 RGR_echTel  HWPYGSGGCQAHGFQGFTVALASICSCAAIAW<font color="blue">ERY</font>HHYCT  
 RGR_proCap  RWPYGSDGCQAHGFQGFVMALTSICSCAAIAW<font color="blue">ERY</font>HHYCT  
 RGR_dasNov  RWPYGSGGCQAHGFQGFVTALASISSSAAIAW<font color="blue">ERC</font>HRHCI  
 RGR_choHof  RWPHGSDSCQAHSFQGFATALASISSSAAIAW<font color="blue">ERY</font>RHHCT 
 RGR_monDom  gene lost
 RGR_macEug  gene lost 
 RGR_ornAna  HWPYGAEGCRLHGFQGFATALASISLSAAIGW<font color="green">DRY</font>LRHCS  
 RGR_anoCar  YWPYGSDGCQIHGFHGFLTALTSISSAAAVAW<font color="green">DRH</font>HQYCT  
 RGR_galGal  YWPYGSEGCQIHGFQGFLTALASISSSAAVAW<font color="green">DRY</font>HHYCT  
 RGR_taeGut  YWPYGSDGCQIHGFQGFLTALASIGSSAAIAW<font color="green">DRY</font>HHYCT  
 RGR_xenTro  YWPYGSEGCQIHGFQGFVAALSSIGSCAAIAW<font color="green">DRY</font>HQYCT  
 RGR_xenLae  YWPYGSEGCQIHGFQGFVAALSSIGSCAAIAW<font color="green">DRY</font>HQYCT  
 RGR_danRer  YWPYGSDGCQTHGFQGFMTALASIHFIAAIAW<font color="green">DRY</font>HQYCT  
 RGR_pimPro  YWPYGSDGCQTHGFQGFMTALASIHFIAAIAW<font color="green">DRY</font>HQYCT
 RGR_takRub  YWPYGSDGCQTHGFQGFVTALASIHFVAAIAW<font color="green">DRY</font>HQYCT  
 RGR_tetNig  YWPYGSEGCQTHGFQGFVTALASIHFVAAIAW<font color="green">DRY</font>HQYCT  
 RGR_gasAcu  YWPYGSDGCQTHGFQGFVTALASIHFIAAIAW<font color="green">DRY</font>HQYCT  
 RGR_oryLat  YWPYGSEGCQTHGFHGFLTALASIHFIAAIAW<font color="green">DRY</font>HQYCT  
 RGR_gadMor  YWPYGSDGCQTHGFQGFTVALASIHFVAAIAW<font color="green">DRY</font>HQYCT  
 RGR_poeRet  YWPFGQEGCNYHAFQGMISVLASISFMAAIAW<font color="green">DRY</font>HQYCT  
 RGR_osmMor  YWPYGSDGCQTHGFQGFMTALASIHFVAAIAW<font color="green">DRY</font>HQYCT  
 RGR_spaAur  yWPYGSDGCQTHGFQGFCTALASIHFIAAIAW<font color="green">DRY</font>HQYCT
 RGR_hipHip  YWPFGQDGCSYHGFQGMISVLASISFMAAIAW<font color="green">DRY</font>HQYCT
 RGR_melAur  yWPFGQDGCAYHGFQGMISILASISFLAAIAW<font color="green">DRY</font>HQYCT
 RGR_calMil  YWPYGSEGCQTHGFHGFLMALASINACAAIAW<font color="green">DRY</font>HQNCS

=== PhyloSNPs in RGR ===

[[Image:Opsin_phyloSNPs.png|left]]

[[Image:Opsin_RGR_phyloRes.png|left|]]

All significant phylogenetic information for RGR -- SNPs that stuck in all descendent clades  -- can be extracted with simple cladesheet methods (described shortly). This involves disentangling sporadic non-adaptve variants from neutral flop-flopping within a reduced alphabet from clade-coherent change. Clade-coherent change is what makes a boreoeuthere a boreoeuthere (or a whatever a whatever).  

PhyloSNPs are residues fixed for considerable branch length that subsequently experience an enduring change on one descendant branch while maintaining the ancestral value in all other descendant species. Because billions of years of branch length are involved (given the current 50 vertebrate genomes available), this change has to have been and continue to be functionally adaptive. Collectively, the set of phyloSNPs on a given internode stem defines at the protein level what is distinctive about the clade and common to it.

The array at left is time-sorted horizontally (with subsorting for noise) and phylo-ordered vertically as indicated by the coloring. Dots mean the amino acid residue in the indicated species agrees with homSap. Starting at the lower left corner, 11 positions in RGR where, at the phylogenetic depth of shark to fish, a signficant change took place in the tetrapod stem prior to tetrapod divergence from lobe-finned fishes and held in tetrapod clade and its outgroups to the present day. For example V>I, G>A, P>A, M>F for the first four. 

These phyloSNPs do not assume or support teleost fish proteins being more 'primitive' or more ancestral than mammal -- indeed fish in general are much more evolved from ancestral state  than human, meaning a random outgroup protein from chondrichthyes will have higher percent identity to mammal. Cartilaginous fish and lamprey nodes play a key role in allocating phyloSNPs: in parsimony it suffices to have the two preceding nodes the same to establish the ancestral state on their interstem. Skate and dogfish ESTs can validate elephantshark genome;  some opsin dara exists for multiple species of lamprey.  There will be phyloSNPs that just make fish fish but that is not the focus here. 

Looking at the lower middle, at 14 positions after the phylogenetic run of shark to platypus, a signficant change took place in the theran stem and held in both sister clades to the present day. For example M>L, F>L, F>L, K>P for the first four. In the lower right, at 1 position in RGR where, at the phylogenetic depth of shark to Afrothere + Xenarthra, a signficant change took place in the boreotheran stem and held in the descendent clade and outgroups to the present day, E/D>G. As RGR is a GPCR signalling protein and the E/DRY motif (which helps prevent false signalling) has been conserved for many trillions of years of branch length. This is an example of an interpretable clade-coherent functional change making a boreoeuthere distinct from Afrotheres, Xenarthra, and everything else.

Colors group residues nearby in the linear sequence that changed at about the same geological time. These are candidates for co-evolving residues where after the first changes, a second makes a compensatory shift. The interactions of residues in different transmembrane helices that touch are another form of adjacency. These are not yet displayed but likely will suggest further co-evolving candidate pairs.

Some phyloSNP positions exhibit more background sporadic variation than others. These can be filtered to only the most pristine cases for purposes of additional bioinformatics or experimental investment. Doubling the number of species with sequenced genomes would have the effect of further refining these distinctions.

RGR has an unusuall high proportion of phyloSNPS at 32 out of 292 residues. Proteins such as PRNP, of the same length but twice the sequence density and more rapidly evolving, appear not to have a single phyloSnp of depth beyond euarchontoglires.

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=== Loss of RGR in marsupials ===

[[Image:Opsin_RGR_active.png|left]]

Notably absent are RGR genes in marsupials; for other genes, marsupial representatives are typically available from 2-3 species. By locating syntenic genes in placental mammals and platypus, the appropriate region of the opossum genome can be identified. However the adjacent orthologs are now on separate autosomal opossum chromosomes, suggesting a translocation has disrupted the RGR genes. None of the individual exons can be found by tblastn of the genome or blastn of the very extensive trace archive coverage. This lack of even pseudogene debris supports the idea of gene loss and decay sometime after marsupial divergence.

The loss of RGR in marsupials further challenges the usual functional explanation given to RGR in placental mammals (a complex with 11-cis-retinol dehydrogenase RDH5 that replenishes cis-retinal at cone and rod opsins). Since marsupials are known from experiment to have normal color and rod vision, either other pathways for replenishment exist or the role of RGR was somewhat different in the ancestor. 

If RGR has 1/5th the quantum efficiency of  rod rhodopsin and 1/100th its abundance, the question arises how it keeps up with bright light replenishment needs. Furthermore, [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12716426 knockout mice] develop a normal retina and RP epithelium without any morphological phenotype (unlike those lacking trans-retinol isomerase RPE65), whereas humans even heterozygous in RGR for Ser66Arg exhibit ERG abnormalities and eventually retinitis pigmentosa and RPE degeneration.

Most experimental work has unfortunately been done on GRY species whereas platypus and earlier diverging species have the more conventional DRY or ERY. Thus the role of RGR could have drastically shifted at the time of marsupial divergence. They lost the gene altogether while placentals retained it but likely with a rather altered signaling properties and functionalities.
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=== Gain of RGR paralog in teleost fish ===

Zebrafish is complicated by having a second diverged copy RGR2 presumably arising from its whole genome duplication. This is less like the tetrapod RGR (51% identity vs 68% relative to chicken, 42% vs 57% relative to human). However it has far more abundant transcripts than its tetrapod-like RGR1. It also has intact signaling region DRY LAKTSPIFHAVLYAYGNEFYRGGVWQ and presumably uses the same Galpha as RGR1. 

Functional partitioning is not clear because paralogs have retina/RPE transcripts; indeed RGR2 arose from a specific [http://www.iovs.org/cgi/pmidlookup?view=long&pmid=17251491 embryonic RPE expression profiling experiment]. Those authors did not realize this was RGR2. Perhaps significantly, RGR1 did not make the list of genes with enhanced RPE expression relative to retina.

RGR2 can also be recovered from 9 species of teleost fish but has no counterpart in chondrichthyes or tetrapods, suggesting by parsimony that a single lineage-specific exon-preserving duplication occured within fish lineage prior to their speciation (rather than arising earlier and being lost from these other lineages). This implies that RGR2 has carved out a distinct niche with selective advantage preserving it for many billions of years of branch length time. 

Despite sequence identity at time of duplication, RGR1 has retained distinctly more ancestral (parental gene) character, evidently by selection that continued by retention of major ancestral functions. Fish RGR2 are evolving more rapidly among themselves than RGR1 yet may shed light on core conserved features of this opsin class:

The two paralogs do not have any indels of phylogenetic significance, though the amino terminus and less-well conserved carboxy terminus have somewhat variable length. Within the Otocephala fish (ie Danio and Pimephales), RGR2 has a 2 residue insertion PA of obscure taxonomic interest as rare cladistic genomic event. RGR2 like RGR1 terminates consistently in all species with basic residues, eg KQK* despite variations in last exon length. The specific function of this cytoplasmic tail motif is unknown. It is unique among all other opsin classes.

The best PDB model for RGR2 is 2ZIY from squid melanopsin [[Opsin evolution|MEL1_todPac]] but this has only 25% sequence identity and significant loop gaps. No RGR2 representatives exist at SwissProt as of Jan 08. However transmembrane sections can be reliably predicted ab initio or by homology. The sole glycosylation site NFT in the 3rd extracellular loop of RGR1 is missing in RGR2. It's not clear what that implies for [http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=19136571 GPCR processing in the ER]. The predicted disulfide at 88-162 CQA-CTL is however invariant. The sole known retinitis pigmentosa mutation site in the second transmembrane helix of human RGR, S66R, is not a conserved residue in RGR2.

 RGR membrane topology: <font color="green">extracellular</font> <font color="red">transmembrane</font> <font color="blue">cytoplasmic</font>
 
 >RGR_homSap               >RGR2_danRer 
 <font color="green">MAETSALPTGFGELE           MASYPLPEGFTDF</font>
 <font color="red">VLAVGMVLLVEcALSGLSLNTL    DMFAFGSALLVGGLLGFFLNAI</font>
 <font color="blue">TIFSFCKTPELRTPCH          SVLAFLRVREMQTPNN</font>
 <font color="red">LLVLSLALADSGI'''S'''LNALVAA     FFIFNLAVADLSLNINGLVAA</font>
 <font color="green">TSSLLRRWPYGSDG'''C'''QAH        YACYLRHWPFGSEG'''C'''QLH</font>
 <font color="red">GFQGFVTALASICSSAAIAW      AFQGMVSILAAISFLGAVAW</font>
 <font color="blue">'''GRY'''HHYCTRSQLAWNSAVS       '''DRY'''HQYCTKQKMFWSTSIT</font>
 <font color="red">LVLFVWLSSAFWAALPLLGWG     ISCLIWILAVFWAAMPLPAIGWG</font>
 <font color="green">HYDYEPLGTC'''C'''TLDYSKGDR'''NFT'''S  VFDFEPLRTC'''C'''TLDYSQGDRGYIT</font>
 <font color="red">FLFTMSFFNFAMPLFITITS      YMLTITVLYLAFPVLVLQSS</font>
 <font color="blue">YSLMEQKLGKSGHLQVNTTLPART  YSAIHAYFKKTHHYRFNTGLPLKA</font>
 <font color="red">LLLGWGPYAILYLYAVIADVT     LLFCWGPYVVVCSLACFEDV</font>
 <font color="green">SISPKL                    SVLSPRL</font>
 <font color="red">QMVPALIA'''K'''MVPTINAINYALG    RMVLPVLA'''K'''TSPIFHAVLYAYG</font>
 <font color="blue">NEM'''VC'''RGIWQCLSPQKREKDRTK   NEF'''YR'''GGVWQFLTGQKSADKKK</font>
 
 Comparative rates of evolution within paralog classes:
 
 RGR2_gasAcu 100%    RGR1_gasAcu 100%
 RGR2_tetNig  87%    RGR1_tetNig  90%
 RGR2_oryLat  82%    RGR1_oryLat  87%
 RGR2_pimPro  71%    RGR1_pimPro  87%
 RGR2_danRer  69%    RGR1_danRer  87%
 
 Signaling regions of RGR2:
 
 RGR2_danRer DRY LAKTSPIFHAVLYAYGNEFYRGGVWQ
 RGR2_tetNig DRY IAKTNPIFNALLYTFGNEFYRGGVWH
 RGR2_gasAcu DRY VAkTNPIFNALLYSFGNEFYRGGVWF
 RGR2_pimPro DRY LAKTSPIFHAAMYAYGNEFYRGGIWQ
 RGR2_oryLat DRY IAKTNPFFNALLYSFGNEFYRGGVWN
 
 Alignment of zebrafish RGR1 and RGR2:
 
 RGR1_danRer  MVTSYPLPEGFSEFDVFSLGSCLLVEGLLGFFLNAVTVIAFLKIRELRTPSNFLVFSLAMADMGISTNATVAAFSSFLRYWPYGSDGCQTHGFQGFMTALASIHFIAAIAWDRYHQYCTRTKLQWSSAITLVLFTWLFTAFWAAMPL--
 RGR2_danRer  .-A........TD..M.AF..A...G.........IS.L...RV..MQ..N..FI.N..V..LSLNI.GL...YACY..H..F..E...L.A...MVSI..A.S.LG.V..........KQ.MF..TS..ISCLI.ILAV.......PA
 
               FGWGEYDYEPLRTCCTLDYSKGDRNYVSYLIPMSIFNMGIQVFVVLSSYQSIDKKFKKTGQAKFNCGTPLKTMLFCWGPYGILAFYAAVENATLVSPKLRMIAPILAKTSPTFNVFVYALGNENYRGGIWQLLTGQKIESPAIENKSK
               I...VF.F............Q...G.IT.MLTITVLYLAFP.L.LQ...SA.HAY....HHYR..T.L...AL.......VVVCSL.CF.DVSVL..R...VL.V......I.HAVL..Y...F....V..F.....SADKKK
''

=== RGR signaling in olfactory bulb and retinal pigmented epithelium ===

RGR opsins in GRY mammals could signal through a heterotrimeric G protein. However from the alignments below, it can be seen that the critical YR portion of the heterotrimeric Galpha binding motif conformational switch is missing in the GRY mammals. This would not affect photoreceptive spectrum but might impact binding or release of substrate. Consequently these opsins will not be able to signal through binding to a Galpha protein. Lacking coupling, such RGR are still opsins but not GPCR.

However, the shift to GRY is boreoeutheres is not satisfactorily described as loss of function because the G itself is invariant over a 1.4 billion years of branch length. Thus it represents an innovation under strong selective pressure whose adaptiveness is not yet understood.

On the flip side, the ERY mammals and DRY vertebrates do seem to have retained a satisfactory switch region (the NYRG region that stands out in the difference alignment below). This suggests ancestral signaling capability has continued to the present day in these species. However it cannot be assumed that signaling takes place in every cell type in which the gene is expressed because significant signaling in only one cell type would assure conservation of the necessary features. 

Which of the [[Opsin_evolution:_transducins|16 vertebrate paralogs of Galpha]] do these DRY RGR use for signaling? In theory, any RGR in any given species could be threaded to a known 3D structure and computationally docked to each of the similarly modeled Galpha subunits of that species, the most favorable fit then being the prediction. That might not be feasible if the responsible region is a cytoplasmic loop not effectively predicted by the 7-transmembrane constraint. More than one binding partner might be possible given that the Galpha are all duplicates of a single ancestral gene whose 3D structure has not changed substantially.

Alternatively, seeking primary sequence correlations from comparative genomics, requires extensive seeding from experimentally known opsin/Galpha binding pairs as classified in an Oct 2008 [http://www.pnas.org/content/105/40/15576.full cnidarian opsin study]. This is not ab initio prediction so much as homology transfer across orthology classes to opsins lacking direct experimental data. Here, RGR has only distant sequence and exon boundary affinities to ciliary imaging opsins with known Galpha partners. 

The purpose served by photoreceptive signaling in the RPE is equally unclear. Signaling capacity may only be important in other cell types -- the Allen brain atlas in mice provides a high resolution sagittal section showing significant RGR expression in the main olfactory bulb and olfactory nerve layer. Expression chips show mouse RGR transcribed in liver, iris, eyecup, ciliary body, and lacrimal gland in addition to retina and RPE. However all the many dozen GenBank mouse transcripts of RGR originate from RPE/choroid or retina, probably because of library bias.

[http://www.iovs.org/cgi/content/full/45/3/769 Expression of chicken RGR occurs in the inner nuclear layer (INL) and retinal ganglion cell layer (RGL); in the pineal gland, RGR mRNA was sparsely observed among pinealocytes in follicles though not in the follicles themselves. A role in circadian rhythm could be postulated. {http://www.fasebj.org/cgi/content/full/20/14/2648 Chicken embryonic RGC] are also known to express melanopsin and Gq transducin (but not ciliary Gt). Two opsins in the same cell complicates the search for signaling partners of RGR.

[[Image:RGRsagittal.jpg]]

One intriguing possibility assuming RGR expression in mouse olfactory node has counterparts in ERY mammals, is Golf (Gs) signaling via type 3 adenylyl cyclase in which elevated cAMP activates CNG membrane conductance channels. While the massive loss of olfactory genes in primates has similar timing to the advent of GRY it leaves mouse olfaction uncorrelated. Mouse of course is also a boreoeuthere.

 The terminus of RGR aligned from 47 available vertebrate sequences showing <font color="brown">GRY</font> <font color="green">ERY</font> and <font color="blue">DRY</font> species:
 
              GPIFMTIPAFFAKSAAIYNPVIYIMMNKQFRNCMLTTICCGK (rhodopsin)           
 <font color="brown">RGR_homSap  SPKLQMVPALIAKMV PTINAINY ALGNEMVCRGIWQCLSPQKREKDRTK       
 RGR_panTro  SPKLQMVPALIAKMV PTINAINY ALGNEMVCRGIWQCLSPQKSEKDRTK   
 RGR_gorGor  SPKLQMVPALIAKMV PTINAINY ALGNEMVCRGIWQCLSPQKSKKDRTK
 RGR_ponPyg  SPKLQMVPALIAKMV PTINAINY ALGNEMVCRGIWQCLSPQKSEKDRTK       
 RGR_macMul  SPKLQMVPALIAKMV PTINAINY ALGNEMVCRGIWQCLSPQKSEKDRAK       
 RGR_papHam  SPKLQMVPALIAKMV PTINAINY ALGNEMVCRGIWQCLSPQKSEKDRAK       
 RGR_nomLeu  SPKLQMVPALIAKMV PTINAVNY ALGNEMVCRGIWQCLSPQKSEKDRAK       
 RGR_calJac  SPKLQMVPALIAKMV PTIDAINY ALGNEMICRGIWQCLSPQKSEKDRTK   
 RGR_tarSyr  SPKLQMVPALIAKTV PTINAYHY ALGSEMVCRGIWQCLSPHSSEHHRAK
 RGR_otoGar  SPKLQMVPALIAKTV PTINAVNY ALGSEMVCRGIWQCLSLQRSKQDGAK       
 RGR_micMur  SPKLQMVPALIAKTV PTINAINY ALGSETVCRGIWQCLSPQRSEQDRAK       
 RGR_tupBel  SPKLQMVPALVAKMV PTVNAVNY ALGSETICRGIWGCLSP KRERDRAR      
 RGR_musMus  SPKLQMVPALIAKTM PTINAINY ALHREMVCRGTWQCLSPQKSKKDRTQ       
 RGR_ratNor  SPKLQMVPALIAKTM PTINAINY ALRSEMVCRGTWQCRSAQKSKQDRTQ       
 RGR_dipOrd  SPKLQMVPALIAKMV PTVNAINY ALCNELLCGGFSLGLLPQKGKQDRTQ       
 RGR_cavPor  SPRLQMVPALIAKTV PTINAINY SLGsevirRGPWQSLEMQRSKQDRT    
 RGR_oryCun  TLKLQMVPALIAKTV PTVNAVNY ALGSEVIRRGIWQCLLPQRSVRGRAQ       
 RGR_ochPri  SPKLLMVPALIAKAV PTVNAINY ALGSEVIRRGIWQCLLPQRSVRDRAQ           
 RGR_bosTau  SPKLQMVPALIAKAV PTVNAMNY ALGSEMVHRGIWQCLSPQRREHSREQ       
 RGR_susScr  SPKLQMVPALIAKMV PTVNAINY ALGGEMVHRGIWQCLSPQRRERDREQ       
 RGR_equCab  SPKLRMVPALVAKTV PTINAVNY ALGSEMLHRGIWQCLSPQKSERDRAQ       
 RGR_myoLuc  PPRLQVVPALIAKMV PTVNAVNY ALGSemvqrGIWQRLSLQrSGWDSAQ
 RGR_pteVam  SPKLQMVPALIAKMA PTINAVNY ALGSEMVQRGIWQCLSPQRSERDHAQ       
 RGR_canFam  PPKLQMVPALIAKAA PTINAIHY ALGGDMVHGGLWQCLSPQRSQPDRAR       
 RGR_felCat  SPKLQMVpaliakaV PTINAINY ALGSEMVHRGIWQCLSPQGSGLDRAR
 RGR_eriEur  SPKLQMVPALIA MV PTVNAVHY VLGSEKVHKGFWQCFSPQRSEQDRAR     
 RGR_sorAra  spklqMVPALIAKTV PTVNALHY GLGS</font>       
 <font color="green">RGR_loxAfr  SPRLQMVPALVAKAV PVINACHY ALGSEVVRGGIWQYLSRQRGESPLRARDRTH  
 RGR_echTel  SPKLQMVPAIVAKAV PIVNACHY ALGNKVLRRGIWQFLSQQSGR PLSSQDRTQ
 RGR_proCap  SPKLQMVPALIAKAV PIVNACHY ALGSETVHRGIWQCLSRQRGESPPRTRDRTQ  
 RGR_choHof  sprlqMVPALIAKTM PTINAFQY ALGSETVCRDIWQCLPRLRSMGRSSGHD   
 RGR_dasNov  SPRLQMVPALIAKTM PTVNALYY ALGRESVHRNAwQLLRGGGAMAAQHA</font>                      
 <font color="blue">RGR_ornAna  SPKLRMIPALIAKTV PVIDAFTY ALRNEDYRGGIWQFLTGQKIERVEVENKIK
 RGR_anoCar  SPKILMIPAVIAKSS PAANALIY ALGNENYQGGIWQFLTGQKIEKAEVDNKTK
 RGR_galGal  SPKYRMIPAIIAKTV PTVDSFVY ALGNENYRGGIWQFLTGQKIEKAEVDSKTK
 RGR_taeGut  PPKYRMIPALIAKTV PTVDAFIY ALGNENYRGGIWQFLTGQKIEKAEVDNKTK
 RGR_xenTro  SPKLRMIPALLAKTS PAVNAYVY GLGNENYRGGIWQYLTGQKLEKAETDNKTK
 RGR_xenLae  SPKLRMMPALLAKIS PAVNAYVY GLGNENYRGGIWLYLTGQKLEKAETDSRTK
 RGR_danRer  SPKLRMIAPILAKTS PTFNVFVY ALGNENYRGGIWQLLTGQKIESPAIENKSK
 RGR_takRub  SPKLRMMAPILAKTC PTINVFLY ALGNENYRGGIWQFLTGEKIEAPQIENKSK
 RGR_tetNig  SPKLRMMAPILAKTC PTVNVFLY ALGNENYRGGIWQFLTGEKIETPQLENKTK
 RGR_gasAcu  STKLRMMAPILAKTS PTFNVFLY ALGNENYRGGIWQLLTGEKIDVPQIENKSK
 RGR_oryLat  SPKIRMIAPILAKTS PTFNPLLY ALGNENYRGGIWQFLTGEKIHVPQDDNKSK
 RGR_gadMor  SPKLRMMAPILAKTA PTFNVFLY ALGNENYRGGIWQLLTGEKIEVPQIENKSK
 RGR_hipHip  SPKLRMILPVLAKTN PIFNALLY SFGNEFYRGGVWHFLTGQKI VDPVVKKSK
 RGR_oncMyk  SPKLRMLLPVLAKTN PIFNAWLY SFGNEFYRGGVWQFLTGQKFTEPVVVKLKGR
 RGR_pimPro  SPKLRMVLPVLAKTS PIFHAAMY AYGNEFYRGGIWQFLTGQK     PADKKK</font>     
              GPIFMTIPAFFAKSA AIYNPVIY IMMNKQFRNCMLTTICCGK (rhodopsin)              
 
[[Image:RGRdiffAlign.jpg]]

=== Local splice migration and exon-skipping in RGR opsins ===

[[Image:Opsin_RGR_earlySpl.png|left]]

RGR in primates may contain an earlier splice acceptor in the second intron resulting in insertion of four amino acids in the extracellular loop EX1 between TM2 and TM3. This is observed in a number of human transcripts but all appear to originate from a single brain tumor sample (eg BC011349). The intronic region is conserved in the UCSC 28-way track but it cannot be a splice acceptor in tarsier, mouse lemur, or tree shrew much less other placentals. For example, in dog, horse and armadillo, translation would cause loss of reading frame -- and horse even has the AG acceptor.  Thus it is difficult to say whether the insert is simply tolerated or has acquired a secondary function. The nucleotide sequence might be conserved as part of a splice enhancer.

A second defective splice isoform has also been [http://www.molvis.org/molvis/v13/a131/ studied] that entirely skips the 6th exon. While exons don't correspond cleanly to transmembrane domains, nevertheless TM7 is lost -- while the altered protein has been proven to be produced abundantly by mass spectroscopy (unlike the vast majority of supposed alternative splices), it cannot function as an opsin. In fact it accumulates extracellularly at the basal boundary of RPE cells primarily in Bruch's membrane, adjacent choriocapillaris, and intercapillary region. The carboxy terminus has been cleaved as well. A role in degenerative eye disease has neither been established nor ruled out.

<br clear="all" />


<pre>Possibilities for upstream splice migration in Euarchonta:

>RGR_ext_homSap VSHRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTR
AGTGTCTCCCACAGGCGCTGGCCCTACGGCTCGGACGGCTGCCAGGCTCACGGCTTCCAGGGCTTTGTGACAGCGTTGGCCAGCATCTGCAGCAGTGCAGCCATCGCATGGGGGCGTTATCACCACTACTGCACCCGT
>RGR_ext_panTro VSHRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTR
AGTGTCTCCCACAGGCGCTGGCCCTACGGCTCGGACGGCTGCCAGGCTCACGGCTTCCAGGGCTTTGTGACAGCGTTGGCCAGCATCTGCAGCAGTGCAGCCATCGCATGGGGGCGCTATCACCACTACTGCACCCGT
>RGR_ext_gorGor VSHRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTR
AGTGTCTCCCACAGGCGCTGGCCCTACGGCTCGGACGGCTGCCAGGCTCACGGCTTCCAGGGCTTTGTGACAGCGTTGGCCAGCATCTGCAGCAGTGCAGCCATCGCATGGGGGCGCTATCACCACTACTGCACCCGT
>RGR_ext_ponPyg VSHRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTR
AGTGTCTCCCACAGGCGCTGGCCCTACGGCTCGGACGGCTGCCAGGCTCACGGTTTCCAGGGCTTTGTGACAGCGTTGGCCAGCATCTGCAGCAGTGCAGCCATCGCGTGGGGGCGCTATCACCACTACTGCACCCGT 
>RGR_ext_nomLeu VSHRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTR
AGTGTCTCCCACAGGCGCTGGCCCTACGGCTCGGACGGCTGCCAGGCTCACGGCTTCCAGGGCTTTGTGACAGCATTAGCCAGCATCTGCAGCAGTGCAGCCATCGCATGGGGGCGCTATCACCACTACTGCACCCGT
>RGR_ext_macMul VSHRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTR
AGTGTCTCCCACAGGCGCTGGCCCTACGGCTCGGACGGCTGCCAGGCTCACGGCTTCCAGGGCTTTGTGACAGCGTTGGCCAGCATCTGCAGCAGTGCAGCTATCGCCTGGGGGCGCTATCACCACTACTGCACCCGT
>RGR_ext_papHam VSHRRWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCTR
AGTGTCTCCCACAGGCGCTGGCCCTACGGCTCAGATGGCTGCCAGGCTCATGGCTTCCAGGGCTTTGTGACAGCGTTGGCCAGCATCTGCAGCAGTGCAGCTATCGCCTGGGGGCGCTATCATCACTACTGCACCCGT
>RGR_ext_calJac VSHRRWPYGSDGCQIHGFQGFVTALASICGSAAIAWGRYHHYCTR
AGTGTCTCCCACAGGCGCTGGCCCTACGGCTCGGACGGCTGCCAGATTCACGGCTTCCAGGGCTTTGTGACAGCGTTGGCCAGCATCTGCGGCAGTGCAGCCATCGCCTGGGGGCGCTATCACCACTACTGCACCCGT
>RGR_ext_tarSyr
GGTGTCTCCCACAGGCGCTGGCCGTACGGCTTGGACGGCTGCCAGGCTCACGGCTTCCAAGGCTTTGTGACAGCTTTGGCCAGCATCGGCGGCAGCGCAGCCATCGCCTGGGGGCGCTATCATCACTACTGCACTCGT
>RGR_ext_otoGar VLHRRWPYGSGGCQAHGFQGFTTALASICGSAAIAWGRYHHYCTR
AGTGTTCTCCACAGGCGCTGGCCCTACGGCTCAGGTGGCTGCCAGGCTCACGGCTTCCAGGGCTTCACGACGGCATTGGCCAGCATCTGCGGCAGCGCAGCCATCGCCTGGGGGCGCTATCACCACTACTGCACCCGT
>RGR_ext_micMur
CGTGTCTCCCACAGGCGCTGGCCCTACGGCTCGGATGGCTGCCAGGCTCACGGCTTCCAGGCTGCGTGACGGTGCTGGCCAGCATCTGCAGCAGCGCGGCCATCGCCTGGGGGCGCTATCACCACTACTGCACCCGT
>RGR_ext_tupBel
CATGTCTTCCACAGGCGCTGGCCCTACGGCTCAGACGGCTGCAAGGTTCATGGCTTCCAGGGCTTCGCAACAGCGTTGGCCAGCATCTCTGGCAGCGCGGCCATCGCCTGGGGGCGCTATCACCAGTACTGCACTCGT
</pre>

=== RGR reference sequences from 51 vertebrates ===
<pre>
>RGR_homSap Homo sapiens (human) 
0 MAETSALPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 RSQLAWNSAVSLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKREKDRTK* 0

>RGR_panTro Pan troglodytes (chimp) 
0 MAETSALPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 RSQLAWNSAISLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMSFFNFAIPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSEKDRTK* 0

>RGR_gorGor Gorilla gorilla (gorilla) 0 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLAPAESGISLNALVGATSTLLG 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 GSTLACKSAVSLVLSGRMSSAFWADLPLLGWGPYDYEPLRTCCTLDYSEADR 2
1 NFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSKKDRTK* 0

>RGR_ponPyg Pongo pygmaeus (orang_abelii) 
0 MAETSALPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 GSQLAWNSAISLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAVLYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSEKDRTK * 0

>RGR_nomLeu Nomascus leucogenys (gibbon) 
0 MAETSVLPTGFGELKLLAGGMGLLAE 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 GSQLAWNSAISLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAVNYALGNEMVCRGIWQCLSPQKSEKDRAK* 0

>RGR_macMul Macaca mulatta (rhesus) 
0 MAETSALPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALIAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 RSQLAWNSAISLVLFVWLSSTFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSEKDRAK* 0

>RGR_papHam Papio hamadryas (baboon) 
0 MAETSALPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNTLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALIAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 2
1 NFTSFLFTMSFFNFAMPLFITITSYSLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTINAINYALGNEMVCRGIWQCLSPQKSEKDRAK* 0

>RGR_calJac Callithrix jacchus (marmoset) 
0 MAESSTLPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNSLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALVAATSSLLR 2
1 RWPYGSDGCQIHGFQGFVTALASICGSAAIAWGRYHHYCT 1
2 GSQLAWNSAISLVLFVWLSSTFWAAFPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMSFFNFAMPLFITITSYRLMEQKLGKSGHLQ 0
0 VNTTLPARTLLLGWGPYAILYLYAVIADVTSISPKLQM 0
0 VPALIAKMVPTIDAINYALGNEMICRGIWQCLSPQKSEKDRTK* 0

>RGR_tarSyr Tarsius syrichta (tarsier) 
0 MAEAGALPAGFGELEVLAVGMVLLVE 1
2 ALSGLSLNSLTIFSFCKTPELRTPCHLLVLSLALADSGISLNALIGATSSLLR 2
1 RWPYGLDGCQAHGFQGFVTALASIGGSAAIAWGRYHHYCT 1
2 GSQLAWNTAISLVLFVWLSYAFWAALPLLGWGHYDYEPLGTCCTLEYSKGDR 2
1 0
0 VNTTLPIRTLMLGWGPYALLYLCAVIADVTSISPKLQM 0
0 VPALIAKTVPTINAYHYALGSEMVCRGIWQCLSPHSSE* 0

>RGR_otoGar Otolemur garnettii (bushbaby) 
0 MAEPGTLPAGFGEIEVLAVGTVLLVE 1
2 2
1 RWPYGSGGCQAHGFQGFTTALASICGSAAIAWGRYHHYCT 1
2 GRPLAWSTAISLVLFVWLSSAFWAALPLLGWGHYDYEPLRTCCTLDYSRGDR 2
1 NFTSFLFTMAFFNFLTPLFITLTSYQLMEQKLRRSGHLQ 0
0 VNTTLPARTLLLGWGPYALLYLYATIADVTSISPKLQM 0
0 VPALIAKTVPTINAVNYALGSEMVCRGIWQCLSLQRSKQDGAK* 0

>RGR_micMur Microcebus murinus (mouse_lemur) 
0 MAEPGTLPTGFRELEVLAVGTVLLVE 1
2 2
1 RWPYGSGGCQAHGFQGFTTALASICGSAAIAWGRYHHYCT 1
2 GSPLAWSTAISLVLFVWLSSAFWAALPLLGWGHYNYEPLGTCCTLDYSRGDR 2
1 NVTSFLFTMAFFNFLIPLFITHTSYQLMEQKLKKSGHLQ 0
0 VNTTLPARTLLLGWGPYALLYLYATVADVTSISPKLQM 0
0 VPALIAKTVPTINAINYALGSETVCRGIWQCLSPQRSEQDRAK* 0

>RGR_tupBel Tupaia belangeri (treeshrew) 
0 MAESGALPSGFGELEVLAVGTVLLVE 1
2 ALSGLSLNSLTVFSFCKSPELRTPSHLLVLSVALADSGISLNALIAATSSLLR 2
1 RWPYGSDGCKVHGFQGFATALASISGSAAIAWGRYHQYCT 1
2 2
1 NFTSFLFTMAFFNFLMPLFITLTSYWLMEEKLRKGGRLQ 0
0 VNTTLPSRTLLLGWGPYALLYLYAAFADVTPLSPKLQM 0
0 VPALVAKMVPTVNAVNYALGSETICRGIWGCLSPKRERDRAR* 0

>RGR_musMus Mus musculus (mouse) 
0 MAATRALPAGLGELEVLAVGTVLLME 1
2 ALSGISLNGLTIFSFCKTPDLRTPSNLLVLSLALADTGISLNALVAAVSSLLR 2
1 RWPHGSEGCQVHGFQGFATALASICGSAAVAWGRYHHYCT 1
2 GRQLAWDTAIPLVLFVWMSSAFWASLPLMGWGHYDYEPVGTCCTLDYSRGDR 2
1 NFISFLFTMAFFNFLVPLFITHTSYRFMEQKFSRSGHLP 0
0 VNTTLPGRMLLLGWGPYALLYLYAAIADVSFISPKLQM 0
0 VPALIAKTMPTINAINYALHREMVCRGTWQCLSPQKSKKDRTQ* 0

>RGR_ratNor Rattus norvegicus (rat) 
0 MTATRALPAGFGELEVLAIGIVLLME 1
2 ALSGISLNGLTIFSFCKTPDLRTPSNLLVLSLALADTGISLNALVAAVSSLLR 2
1 RWPHGSEGCRVHGFQGFATALASICGSAAIAWGRYHHYCT 1
2 GRQLAWDTAIPLVLFVWLSSAFWASLPLMGWGHYDYEPVGTCCTLDYSRGDR 2
1 NFISFLFTMAFFNFLVPLFITHTSYRFMEQKLSRSGHLQ 0
0 VNTTLPGRMLLLGWGPYALLYLYAAVADVSFISPKLQM 0
0 VPALIAKTMPTINAINYALRSEMVCRGTWQCRSAQKSKQDRTQ* 0

>RGR_speTri Spermophilus tridecemlineatus (ground_squirrel) 
0 MAETAALPAGFGELEVLAVGTVLLVE 1
2 ALSGLSLNGLTIFSFCKTPELRTPNHLLLLSLAVADSGISLNALIAAISSLLR 2
1 RWPYGSDGCQAHGFQGFVTALSSICGSAAIAWGRYHHYCT 1
2 GSQLAWNTAIPLVLFVWLSSTFWAALPLLGWGHYDYEPLGTCCTLDYSRGDR 2
1 NFISFLFTMAFFNFFVPLFITLTSYRLMEQKLARSGHLQ 0
0 0
0 * 0

>RGR_dipOrd Dipodomys ordii (kangaroo_rat) 
0 MATSGDLPTGFGELEVLTVGTVLLVE 1
2 ALSGLSLNTLTIFSFCKTPELRTPIHLLDLSLAVADSGISLNALIAAISSLEW 2
1 HWPYGLEGCQAHGFQGFVTALASISGSAAIAWGRCHHHCT 1
2 GSLLGWDTAVSLVIFVWLSSAFWAALPLLGWGHYNYEPLGTCCTLDYSRGDR 2
1 NFTSFLFTMAFFNFLVPLFITLTSYQLMKQKFARSGRLQ 0
0 VNTTLPTRTLLLGWGPYALLYFYAAIMDVNSISPKLQM 0
0 VPALIAKMVPTVNAINYALCNELLCGGFSLGLLPQKGKQDRTQ* 0

>RGR_cavPor Cavia porcellus (guinea_pig) 
0 MATSEALPAGFGELEVLAVGTVLLLE 1
2 GLCGLSLNGLTVVSFWKSPALRTPNHLLVLSLALADSGLSLNALVAAGSSLLR 2
1 HWPGSGHCQALGFQGFTTALASISGTAALSWGRHQQCCT 1
2 RGRLTWSTAVPLVLFVWLSSAFWAALPLLGWGRYDYEPLGTCCTLDYSTGDR 2
1 NFTSFLFTMAFFNFLVPLFITVTSCQLMERHLARSSRLQ 0
0 VSVRQPARTLLLCWSPYALLYLYAVLADAHTLSPRLQM 0
0 VPALIAKTVPTIYSLGRGPWQSLEMQRSKQD* 0

>RGR_oryCun Oryctolagus cuniculus (rabbit) 
0 MAEPGTLPPGFEELEVLAVGTVLLVE 1
2 ALSGLSLNGLTIFSFCKTPELWTPSHLLVLSLAVADSGISLNALIAAVSSLLR 2
1 RWPYGSDGCQAHGFQGFATALASICGSAAIAWGRYHHYCT 1
2 GSQLAWNTAVLLVLFVWLSSVFWAALPLLGWGHYDYEPLGTCCTLDYSRGDR 2
1 NFISFLITMAFFNFLMPLFITLTSYSLMEQKLSKSGRLQ 0
0 VNTTLPGRTLLFCWGPYAVLYLCAAVADMSSITLKLQM 0
0 VPALIAKTVPTVNAVNYALGSEVIRRGIWQCLLPQRSVRGRAQ* 0

>RGR_ochPri Ochotona princeps (pika) 
0 MAEPGTLPPGFEELEVLAVGTVLLVE 1
2 ALTGLSLNSLTIFSFCTSPELRTPSHLLVLSLALADSGVSLNALAAATASLLR 2
1 RWPYGSDGCQAHGFQGFATALASICGSAAIAWGRYHHYCT 1
2 GSQLAWNTAVLLVLFVWLSSVFWAALPLLGWGHYDYEPLGTCCTLDYSRGDR 2
1 NFISFLVTMAFFNFLMPLFIMLTSYSLMEQKLAKSGRLQ 0
0 VNTTLPARTLLFCWGPYAILCLCATVMDMSTVSPKLLM 0
0 VPALIAKAVPTVNAINYALGSEVIRRGIWQCLLPQRSVRDRAQ* 0

>RGR_canFam Canis familiaris (dog) 
0 MADSGALPAGFGELEVLAVGTVLLVE 1
2 ALTGLCLNGLTILSFCKTPELRTPTHLLVLSLAVADTGISLNALVAAISSLLR 2
1 RWPYGPDGCQAHGFQGFATALASICSSAALAWGRYHHYCT 1
2 RGQLAWNTAISLVLCVWLSSVFWAALPLLGWGRYDYEPLGTCCTLDYSRVDR 2
1 NFTSYLFTMAFFNFFLPLLITLVSYRLMEQKLKKPGHLQ 0
0 VSTTVPARTLLLCWGPYALLYLYATVADVRSVPPKLQM 0
0 VPALIAKAAPTINAIHYALGGDMVHGGLWQCLSPQRSQPDRAR* 0

>RGR_felCat Felis catus (cat) 
0 MAESGSLPTGFGELEVLAVGMVLLVE 1
2 2
1 RWPYGSNGCQAHGFQGFVTALASICSSAAIAWGRYHHYCS 1
2 GSQLAWNTAISLVICVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSRGDR 2
1 NFTSFLFTMAFFNFFMPLFITFISYRLMEQKLRKTGHLQ 0
0 VNTTLPARTLLFGWGPYALLYLYATIADVSSVSPKLQM 0
0 VPTINAINYALGSEMVHRGIWQCLSPQGSGLDRAR* 0

>RGR_bosTau Bos taurus (cow) 
0 MAESGTLPTGFGELEVLAVGTVLLVE 1
2 ALSGLSLNILTILSFCKTPELRTPSHLLVLSLALADSGISLNALVAATSSLLR 2
1 RWPYGSEGCQAHGFQGFVTALASICSSAAVAWGRYHHFCT 1
2 GSRLDWNTAVSLVFFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSRGDR 2
1 NFTSFLFTMAFFNFLLPLFITVVSYRLMEQKLGKTSRPP 0
0 VNTVLPARTLLLGWGPYALLYLYATIADATSISPKLQM 0
0 VPALIAKAVPTVNAMNYALGSEMVHRGIWQCLSPQRREHSREQ* 0

>RGR_turTru Tursiops truncatus (dolphin) 
0 MAESGALPSGFGELEVLAVGTVLLVE 1
2 ALSGLSLNSLTILCFCKNPELRTPSHLLVLSLALSDSGISLNALMAATSSLLR 2
1 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 GSRLDWNTAVSLVFFVWLSSAFWATLPLLGWGHYDREPLGTCCTLDYSRRDR 2
1 NFTSFLFTMAFFNFLLPLFITVISYRLMEQKLGKTGRPP 0
0 VNTVLPARTLLFGWGPYALLYLYAAVADVTSISPKLQM 0
0 * 0

>RGR_susScr Sus scrofa (pig) 
0 MAEPGALPTGFGELEVLAVGTLLLVE 1
2 ALSGLSLNSLTILSFCKTPELRTPSHLLVLSLALADSGISLNAFVAATSSLLR 2
1 RWPYGSEGCQAHGFQGFATALASICSSAAIAWGRYHHYCT 1
2 RSRLDWNTAVSLVFFVWLSSTFWAALPLLGWGHYDYEPLGTCCTLDYSRVDR 2
1 NFTSFLFTMAFFNFLLPLFITVTSYRLMEQKLGKTGRPP 0
0 VNTILPARTLMLAWGPYALLYLYATFADVTSISPKLQM 0
0 VPALIAKMVPTVNAINYALGGEMVHRGIWQCLSPQRRERDREQ* 0

>RGR_vicVic Vicugna vicugna (vicugna) 
0 MAESRALPTGFGELEVLAVGMVLLVE 1
2 ALSGLSLNSLTILSFCKTPELRTPNHLLVLSLALADSGISLNALVAATSSLLR 2
1 1
2 GSRLDWNTAVSLVFFVWLSSTCWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 0
0 0
0 * 0

>RGR_equCab Equus caballus (horse) 
0 MAESGSLPTGFRELEVLAVGTVLLVE 1
2 ALAGLSLNSLTILSFCKTPELRTPSHLLVLSLAVADSGLSLNALVAATSSLLR 2
1 RWPYGSEGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT 1
2 RSRLAWNTAVFLVFFVWLSSTFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLLTMAFFNLLLPLLITLTSYRLMEQKLGKTGQLQ 0
0 VNTTLPARTLLLCWGPYALLYLYATVADATSISPKLRM 0
0 VPALVAKTVPTINAVNYALGSEMLHRGIWQCLSPQKSERDRAQ* 0

>RGR_myoLuc Myotis lucifugus (microbat) 
0 MAEAGSLPTGFGELEVLAVGVVLLVE 1
2 ALTGLSLNSLTIFSFCTSPELRTPSHLLVLSLALADSGVSLNALAAATASLLR 2
1 RWPYGSGGCQAHGFQGFAAALASICGSAAVAWGRYHHYCT 1
2 GSRLAWRTAASLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCSLGYARGSR 2
1 NFTSFLFLMAFFNFLLPLFITFTSYRLMEQKLGRTRPPQ 0
0 VNTTLPARTLLLGWGPYALLHLCAALAGTALIPPRLQV 0
0 VPALIAKMVPTVNAVNYALGSGIWQRLSLQ* 0

>RGR_pteVam Pteropus vampyrus (macrobat) 
0 MAESRSLPTVFWELEVLAVGTVLMVE 1
2 ALSGLSLNSLTILSFCKNPELRTPIHLLVLSLALADSGISLNALIAATSSLLR 2
1 RWPFGPDGCQAHGFQGFATALASICSSAAIAWGRYHHYCT 1
2 GSRLAWNTAVSLVLFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSRRDR 2
1 NFTSFLFTMAFFNFVLPLFITLTSYQLMEQKLGKTGHPQ 0
0 VNTTLPARTLMLCWGPYALLYLYAAVMDVASISPKLQM 0
0 VPALIAKMAPTINAVNYALGSEMVQRGIWQCLSPQRSERDHAQ* 0

>RGR_sorAra Sorex araneus (shrew) 
0 MTESGALPAGFKELKMLAVGTLLLWG 1
2 2
1 RWPFGPDGCQAHGFQGFATALASICSSAAIAWGRYHHYCT 1
2 GRQLAWDVAIALVIFVWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSRGGR 2
1 NFVSFLFTMAFFNFLLPLFITVTSYRLMEQKLGKMGQPQ 0
0 0
0 VPALIAKTVPTVNALHYGLGSGMVQNGFRKGLWLQRRERERAL* 0

>RGR_eriEur Erinaceus europaeus (hedgehog) 
0 1
2 2
1 RWPYGSDGCQAHGFQGFVMALASICSSAAIAWGRYHHHCT 1
2 RSRLAWNTAVFLVFFVWVSSVFWAALPLLGWGHYDYEPLGTCCTLDYSSGDR 2
1 NFISFLFTMAFFNFLLPLFITLISYQLMEQKLRKTGHPQ 0
0 VNTTLPARTLLLGWGPYALLYLYAVIADVALLSPKLQM 0
0 VPALIAMVPTVNAVHYVLGSEKVHKGFWQCFSPQRSEQDRAR* 0

>RGR_loxAfr Loxodonta africana (elephant) 
0 MAEPGHLPAGFQELEVLTVGTVLLLE 1
2 ALSGLSLNGLTILSFCKIPELRTPGHLLVLSLALADSGISLNALVAAMSSLRR 2
1 RWPYGSDGCQAHGFQGFVTALASICSCAAIAWERYHHYCT 1
2 RSRLAWSSASALVLFVWLSSAFWAALPLLGWGRYNYEPLGTCCTLDYSRGDR 2
1 NSTSFLLTMAFFNFLLPLFITLTSYRLMEQKLKKKGPLQ 0
0 VNTTLPARTLLLGWGPYALLYLCAAATDMTSISPRLQM 0
0 VPALVAKAVPVINACHYALGSEVVRGGIWQYLSRQRGESPLRARDRTH* 0

>RGR_proCap Procavia capensis (hyrax) 
0 MADPRPLPTGFGELEVLTVGTVLLVE 1
2 ALSGLSLNGLTILSFYKIPELRTPGHLLVLNLALADSGMSLNALVAAVSSLRG 2
1 RWPYGSDGCQAHGFQGFVMALTSICSCAAIAWERYHHYCT 1
2 GSKLAWSSAGALVLFMWLSSAFWAALPLLGWGRYNYEPLGTCCTLDYSRGDR 2
1 NSTSFLFTMAFFNFLLPLFITLASYRLMEQKLKKEGPLQ 0
0 VNTTLPARTLLLGWGPYALLYLYTAITDVNSISPKLQM 0
0 VPALIAKAVPIVNACHYALGSETVHRGIWQCLSRQRGESPPRTRDRTQ* 0

>RGR_echTel Echinops telfairi (tenrec) 
0 MVEPRTLPPGFGELEVLAVGTVLLVE 1
2 2
1 HWPYGSGGCQAHGFQGFTVALASICSCAAIAWERYHHYCT 1
2 GSQFTWSSASTLVLFMWLSSAFWAALPLLGWGHYDYEPLGTCCTLDYSKGDR 2
1 NFTSFLFTMTFFNFSMPILVTLTSYQLMQQKLKKSGPLQ 0
0 VNTTLPTRTLLLGWGPYALLYLCAACTDVTGISPKLQM 0
0 VPAIVAKAVPIVNACHYALGNKVLRRGIWQFLSQQSGRQDRTQ* 0

>RGR_dasNov Dasypus novemcinctus (armadillo) 
0 MAGSGVLPPGFGELEVLAVGTVLLVE 1
2 ALSGLVLNGLAIISFCKTPELRSPSRLLVLSLALADSGVSLNALVAATSSLLR 2
1 RWPYGSGGCQAHGFQGFVTALASISSSAAIAWERCHRHCI 1
2 GRRLAWSTAGCLVLCLWMAAAFWAALPLLGWGLYDYEPLGTCCTLDYSRGDR 2
1 NFISFLVTLALFNFFLPLLIMLTSYRLMAQKLKRSGHVQ 0
0 VSTALPGRLLLLGWGPYALLYLYAAVADATSLSPRLQM 0
0 VPALIAKTMPTVNALYYALGRESVHRNA* 0

>RGR_choHof Choloepus hoffmanni (sloth) 
0 MAESRVLPTGFGELEVLAVGIVLLVE 1
2 ALSGLTLNGLTLFSFCKTPELQRPSHLLVLSLALADSGVSLNALLAATASLIG 2
1 RWPHGSDSCQAHSFQGFATALASISSSAAIAWERYRHHCT 1
2 GSQLSWSTAGSLVLCVWLSSVFWATLPILGWGHYDYEPLGTCCTLGYSRGDR 2
1 0
0 0
0 VPALIAKTMPTINAFQYALGSETVCRDIWQCLPRLRSMGRSSGHD* 0

>RGR_ornAna Ornithorhynchus anatinus (platypus) 
0 1
2 ALLGLCLNGLTIASFRKIKELRTPSNLLVVSLALADSGICLNALMAALSSFLR 2
1 HWPYGAEGCRLHGFQGFATALASISLSAAIGWDRYLRHCS 1
2 RSKPQWGTAVSTVLFAWGFSAFWSMMPILGWGQYDYEPLRTCCTLDYSKGDR 2
1 NFTTYLFAVAFFNFVIPLFIMLTSYQSIEQRFKKSGLFK 0
0 LNTRLPTRTLLFCWGPYALLCFYATVENVTFISPKLRM 0
0 IPALIAKTVPVIDAFTYALRNEDYRGGIWQFLTGQKIERVEVENKIK* 0

>RGR_anoCar Anolis carolinensis (lizard) 
0 MVTTAYPVPEGFTDLEVFVIGTALLVE 1
2 ALLGFSLNMLTIVSFWKIKELRTPGNFLVFNLALSDCGICFNAFIAAFSSFLR 2
1 YWPYGSDGCQIHGFHGFLTALTSISSAAAVAWDRHHQYCT 1
2 GNKLQWGSVIPMTIFLWLFSGFWAAMPLLGWGEYDYEPLRTCCTLDYTKGDR 2
1 NYITYLIPLALFHFMIPGFIMLTAYQAIDHKFKKTGQFK 0
0 FNTGLPVKSLVICWGPYSFLCFYAAVESVTFISPKILM 0
0 IPAVIAKSSPAANALIYALGNENYQGGIWQFLTGQKIEKAEVDNKTK* 0

>RGR_galGal Gallus gallus (chicken) 
0 MVTSHPLPEGFTEIEVFAIGTALLVE 1
2 ALLGFCLNGLTIISFRKIKELRTPSNLLVLSIALADCGICINAFIAAFSSFLR 2
1 YWPYGSEGCQIHGFQGFLTALASISSSAAVAWDRYHHYCT 1
2 RSKLQWSTAISMMVFAWLFAAFWATMPLLGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYITFLFALSIFNFMIPGFIMMTAYQSIHQKFKKSGHYK 0
0 FNTGLPLKTLVICWGPYCLLSFYAAIENVMFISPKYRM 0
0 IPAIIAKTVPTVDSFVYALGNENYRGGIWQFLTGQKIEKAEVDSKTK* 0

>RGR_taeGut Taeniopygia guttata (finch) 
0 MVTAHPLPEGFTEIEVFAIGTALLVE 1
2 ALLGFCLNGLTIISFRKIKELRTPSNLLVLSIALADCGICINAFIAAFSSFLR 2
1 YWPYGSDGCQIHGFQGFLTALASIGSSAAIAWDRYHHYCT 1
2 RSRLQWSTAVSMMVFAWLFAAFWSVMPLLGWGKYDYEPLRTCCTLDYSKGDR 2
1 NYVTFLFALSTFNFMIPGFIMMTAYQSIHQKFRKTGHFK 0
0 FNTGLPLKTLVICWGPYCLLCTYAAVENVMFIPPKYRM 0
0 IPALIAKTVPTVDAFIYALGNENYRGGIWQFLTGQKIEKAEVDNKTK* 0

>RGR_xenTro Xenopus tropicalis (frog) 
0 MVTSYPLPEGFTETEVFAIGTTLLVE 1
2 ALLGLLLNGLTLLSFYKIRELRTPSNLFIISLAVADTGLCLNAFVAAFSSFLR 2
1 YWPYGSEGCQIHGFQGFVAALSSIGSCAAIAWDRYHQYCT 1
2 RSKLHWSTAVSVVFFIWGFSAFWSAMPLFGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYISYLFTMAFFEFLVPLFILMTAYQSIYQKMKKSGQIR 0
0 FNTSMPVKSLVFCWGPYCLLCFYAVIQDATILSPKLRM 0
0 IPALLAKTSPAVNAYVYGLGNENYRGGIWQYLTGQKLEKAETDNKTK* 0

>RGR_xenLae Xenopus laevis (frog) NM_001092855 mRNA
0 MVTSYPLPEGFTETEVFAIGTTLLIE 1
2 ALLGLLLNGLTLLSFYKIRELRTPSNLFIISLAVADTGLCLNAFVAAFSSFLR 2
1 YWPYGSEGCQIHGFQGFVAALSSIGSCAAIAWDRYHQYCT 1
2 RSKLHWGTAVSMVLFVWGFSAFWSAMPLFGWGEYDYEPLRTCCTLDYSKGDR 2
1 NFTSFLFTMAFFEFLVPVFILLTAYQSIYQKMKKSGQIR 0
0 LNTSMPVKSLVFCWGPYCLLCFYAVIQDATILSPKLRM 0
0 MPALLAKISPAVNAYVYGLGNENYRGGIWLYLTGQKLEKAETDSRTK* 0

>RGR1_danRer Danio rerio (zebrafish) 
0 MVTSYPLPEGFSEFDVFSLGSCLLVE 1
2 GLLGFFLNAVTVIAFLKIRELRTPSNFLVFSLAMADMGISTNATVAAFSSFLR 2
1 YWPYGSDGCQTHGFQGFMTALASIHFIAAIAWDRYHQYCT 1
2 RTKLQWSSAITLVLFTWLFTAFWAAMPLFGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYVSYLIPMSIFNMGIQVFVVLSSYQSIDKKFKKTGQAK 0
0 FNCGTPLKTMLFCWGPYGILAFYAAVENATLVSPKLRM 0
0 IAPILAKTSPTFNVFVYALGNENYRGGIWQLLTGQKIESPAIENKSK* 0

>RGR1_takRub Takifugu rubripes (fugu) 
0 MVSSYPLPEGFSDFDVFSLGSCLLVE 1
2 GLLGFFLNAVTVVAFLKVRELRTPSNFLVFSLALADMGISMNATIAAFSSFLR 2
1 YWPYGSDGCQTHGFQGFVTALASIHFVAAIAWDRYHQYCT 1
2 RTKLQWSSAITLAVFIWLFCAFWSAMPLIGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYVSYLIPMAIFNMVIQVFVVMSSYQSIAEKFKKTGNPR 0
0 FNPSTPLKAMLLCWGPYGILAFYAAVENANLVSPKLRM 0
0 MAPILAKTCPTINVFLYALGNENYRGGIWQFLTGEKIEAPQIENKSK* 0

>RGR1_tetNig Tetraodon nigroviridis (pufferfish) 
0 MVSSYPLPEGFSDFDVFSLGSCLLVE 1
2 GLLGFFLNAVTVVAFFKVRELRTPSNFLVFSLAMADMGISMNATVAAFSSFLR 2
1 YWPYGSEGCQTHGFQGFVTALASIHFVAAIAWDRYHQYCT 1
2 RTKLQWSSAITLAVFIWLFCAFWSAMPLIGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYVSYLVPMAIFNMVIQVFVVMSSYQSIAEKFKKTGNPR 0
0 FNPNTPLKAMLLCWGPYGILAFYAAVENANLVSPKLRM 0
0 MAPILAKTCPTVNVFLYALGNENYRGGIWQFLTGEKIETPQLENKTK* 0

>RGR1_gasAcu Gasterosteus aculeatus (stickleback) 
0 MVSSYPLPDGFTDFDVFSLGSCLLVE 1
2 GLLGILLNAVTIAAFLKVRELRTPSNFLVFSLAVADIGISMNATIAAFSSFLR 2
1 YWPYGSDGCQTHGFQGFVTALASIHFIAAIAWDRYHQYCT 1
2 RTKLQWSSAITLAVFVWLFTAFWSAMPLIGWGEYDYEPLRTCCTLDYTKGDR 2
1 NYVSYLIPMAIFNMAIQVFVVMSSYQSIAQKFKKTGNPR 0
0 FNPNTPLKAMLFCWGPYGILAFYAAVENATLVSTKLRM 0
0 MAPILAKTSPTFNVFLYALGNENYRGGIWQLLTGEKIDVPQIENKSK* 0

>RGR1_oryLat Oryzias latipes (medaka) 
0 MATSYPLPEGFSEFDVFSLGSCLLVE 1
2 GLLGIFLNSVTIVAFLKVRELRTPSNFLVFSLAMADIGISMNATIAAFSSFLR 2
1 YWPYGSEGCQTHGFHGFLTALASIHFIAAIAWDRYHQYCT 1
2 RTKLQWSTAITLAVLVWIFTAFWAAMPLIGWGEYDYEPLRTCCTLDISKGDR 2
1 NYVSYVIPMSIFNMGIQVFVVMSSYQSIAQKFQKTGNPR 0
0 FNASTPLKTLLFCWGPYGILAFYAAVADANLVSPKIRM 0
0 IAPILAKTSPTFNPLLYALGNENYRGGIWQFLTGEKIHVPQDDNKSK* 0

>RGR1_gadMor Gadus morhua (cod) ES469757
0 MVSAYPLPEGFSDFDVFSFGSFLLVE 1
2 GLLGIILNAVTIVAFCKVKELRTPSNFLVFSLAMADIGISMNASVAAFSSFLR 2
1 YWPYGSDGCQTHGFQGFTVALASIHFVAAIAWDRYHQYCT 1
2 RTELQWSSAVTLSVFIWLFSAFWSAMPLIGWGTYDYEPLRSCCTLDYTKGDR 2
1 NYVSYLIPMTVFNMVVQIFVVMSSYQSIDQKFKKTAKPK 0
0 FNARTPLKTLLFCWGPYGILAFYAAIENASLVSPKLRM 0
0 MAPILAKTAPTFNVFLYALGNENYRGGIWQLLTGEKIVPQEVPQIENKSK* 0

>RGR1_pimPro Pimephales promela DT198813 frag
0 MVTYPLPEGFSDFDVFSLGSCLLVE 1
2 GLLGFFLNAVTVVAFLKIRELRTPSNFLVFSLAMADMGISMNATVAAFSSFLR 2
1 YWPYGSDGCQTHGFQGFMTALASIHFIAAIAWDRYHQYCT 1
2 RTKLQWSSAITLVIFIWLFTAFWSAMPLIGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYVSYLIPMSIFNMGIQVFVVLSSYQSIERKFQKSGQAK 0
0 FNCSTPLKTMLFCWGPYGILAFYAAVENATLVSPKLRM 0
0 LAPILA

>RGR1_osmMor Osmerus mordax (smelt) EL524757 frag
0 MVSSYPLPDGFSDFDVFSLGSCLLVE 1
2 GLLGFFLNAVTVVAFLKVRELRTPSNFLVFSLALADMGISSNATIAAFSSFLR 2
1 YWPYGSDGCQTHGFQGFMTALASIHFVAAIAWDRYHQYCT 1
2 RTKLQWSSAITLVMFIWLFTAFWSAIPLIGWGEYDYEPLRTCCTLDYSKGDR 2
1 NYVSYLIPMAIFNMAIQIFVVLSSYQSIGEK

>RGR_calMil Callorhinchus milii (elephantfish) frag
0   EGFTDFEVFGLGTALLVE 1
2 GLVGLLLNGLTLLAFYKIKELRTPSNLLITSLALSDFGISMNAFIAAFSSFLR 2
1 YWPYGSEGCQTHGFHGFLMALASINACAAIAWDRYHQNCS 1
2 RSRLQWSSAITVTVFIWGIAAFWSAMPLLGWGVYDYEPLRTCCTLDYSKGDR 2
1 NFISFFIIMGSFEFIFPIFIMLSSYQSCKSKFKKNGQVK 0
0 FNTGLPVKTLIFCWGPYSLLCFYATIENITILSPKLRM 0
0 * 0

>RGR_petMar Petromyzon marinus (lamprey) frag, did not make assembly
2 ALLGFVLCGLTLLTFLCVSDARTPSHLLLLNLSLADLGVCSNAFIAAMSSFLR 2
2 GARTRWSTALCLCAWTWLSSAFWAAMPLVGWGRYDYEPLHSCCTLDYSQADG 2

>RGRa_cioInt Ciona intestinalis (tunicate) Ci-opsin3 mRNA 0.2.0.2.1.0.0 PPT1 NOMO2+ FOXC2- FAHD1- AB079882 12687683 289 aa larval visual cycle photoisomerase last 4 introns like RGR
0 MEVNDKRVYGVLMGLL 1
2 GLLTITGYSLLFVIFAKRPDLKKKNKFLLSLATSDLLITVHVFASTIAAFAPQWPFGDLGCQ 0
0 VDAFIGMAPTFISIAGAALIAKDKYYRFCKPKM 1
2 MVGRNYSFHVYLTWTMGIIGGALPFIGFGRYGFETDDVTWRTGCLLDFKSISA 2
1 KYSFYIILISTVWFVWPVYKLVSSYMKISTKINKFYP 0
0 LLFVVPVQMAIGLLPYAIYAMVSITIGVSAVPYFCVVINN 0
0 LAAKVFVGSNPFIYIYFDPELRESCKQIFCSPPAPTNDKISEDSKDE* 0

>RGRb_cioInt AB078611 12373590 entire neural tube CiNut
0 MEIDFGFARTVYGVALLLM 1
2 VFITLLGYAVYFGAIWRSKTLQTRHIWLTSLACGDIIMMVHLILESLSSLGMGHRPRQNFECQ 0
0 VGALVGLFSGYVTIASITWIAIDRYYRQCKPEK 1
2 VGVNYCFYVIIVWAMSFLAASGPALGFGAYESAEENTVKCLIDLNKKDT 2
1 NSRLYIILVSAVWFVYPFVKMILYNKKLVQEAKEPQP 0
0 MAFAVPLTFFLCYLPFAIYASLKITVGLPPLNSMVVASIY 0
0 MLPKVISVVNPYLYMRSDPELLAACRHVVGLTDGKKAV* 0

>RGRa_cioSav Ciona savignyi (tunicate) Ci-opsin3 mRNA 0.2.0.2.1.0.0 new 68% 288 aa larval visual cycle photoisomerase
0 MDFSSKRTYGIAMAAL 1
2 GFIAWVGYGLLFVIFAKSPDLKKKNRFLFSLAVSDLLITIHVVASVVASFQSEWPFGSIGCQ 0
0 LDAFIGMAPTFISIAGAALVAKDKYYRICKPKM 1
2 LVGRNYSFSIYANWTLGIIGGLLPFFGFGQYGFETDDLSLRTGCLLDFKTVSA 2
1 KYRFYIVFISLVWFVWPLYKLTSHYIKISAKLDRFHP 0
0 LMFVVPLQMLVSLLPYAIYAMISITVGVSSAPYYLVAVNN 0
0 IAAKVFIGTNPFIYIYFDPELRLACKNLFKYSSTPVQDQIQDKKDE* 0
</pre>

=== RGR2 reference sequences from 9 teleost fish ===
<pre>
>RGR2_danRer zebrafish NM_001024436 embryonic RPE, brain, gut, embryo PA indel
0 MASYPLPEGFTDFDMFAFGSALLVG 1
2 GLLGFFLNAISVLAFLRVREMQTPNNFFIFNLAVADLSLNINGLVAAYACYLR 2
1 HWPFGSEGCQLHAFQGMVSILAAISFLGAVAWDRYHQYCT 1
2 KQKMFWSTSITISCLIWILAVFWAAMPLPAIGWGVFDFEPLRTCCTLDYSQGDR 2 
1 GYITYMLTITVLYLAFPVLVLQSSYSAIHAYFKKTHHYR 0
0 FNTGLPLKALLFCWGPYVVVCSLACFEDVSVLSPRLRM 0
0 VLPVLAKTSPIFHAVLYAYGNEFYRGGVWQFLTGQKSADKKK* 0

>RGR2_pimPro Pimephales promelas liver brain PA indel
0 MASYALPEGFSDFDMFAFGSALLVG 1
2 GLLGFFLNLISVLAFLRVREIQTPNNFFIFNLAVADLSLNINGLVAAYASYLR 2
1 YWPFGSEGCQIHGFQGMVSILASISFLGAIAWDRYHLYCT 1
2 KQKMFWSTSGTISALIWILAVFWAALPLPAIGWGVFDFEPMRTCCTLDYTIGDR 2
1 NYISYMLTITVLYLAFPVLIMQSSYNGIYAHFKKTHHFK 0
0 FNTGLPLKMLLFCWGPYVLMCTYACFENASLVSPKLRM 0
0 VLPVLAKTSPIFHAAMYAYGNEFYRGGIWQFLTGQKPADKKK* 0

>RGR2_tetNig Tetraodon nigroviridis eyes
0 MAAYTLPEGFTEFDMFTFGTALLVG 1
2 GVLGFFLNAISIVSFLTVKEMRNPSNFFVFNLALADISLNVNGLIAAYASYLR 2
1 YWPFGQDGCSYHAFHGMISVLASISFMAAIAWDRYHQYCT 1
2 RQKLFWSTTLTMSSIIWILSIFWSAVPLMGWGVYDFEPMRTCCTLDYTRGDR 2
1 DYVTYMLTLVVLYLTFPAATMWSCYDSIYKHFKKVHQHR 0
0 FNTSMPLRVLLVCWGPYVVMCVYACFENVKVVSPKLRM 0
0 LLPVIAKTNPIFNALLYTFGNEFYRGGVWHFLTGHKIVDPVLKKSK* 0

>RGR2_gasAcu Gasterosteus aculeatus eye
0 MAAFALPEGFTEFDMFTFGSALLVG 1
2 GLIGFFLNAISIASFLRVKEMWNPSNFFVFNLAVADICLNVNGLTAAYASYLR 2
1 YWPFGQDGCTFHAFQGMIAVLASISFMGVIAWDRYHQYCT 1
2 RQKLFWSTTLTMSAIIWILSIFWAAVPLMGWGVYDFEPMRTCCTLDYTKGDR 2
1 DYVTYMLTLVFLYLMFPALTMWSCYDAIHKHFKKIHLHK 0
0 FNTSTPLRVLLMCWGPYVLMCIYACFENVKVVSPKLRMx 0
0 LLPVVAkTNPIFNALLYSFGNEFYRGGVWHFLTGQKMVDPVVKKSK* 0

>RGR2_oryLat Oryzias latipes (medaka) whole embryo 68% identical RGR2_danRer
0 MGTHTLPEGFTDFDMFTFGSALLVG 1
2 GLLGFFLNAISILAFLRVKEMRSPSSFLVFNLALADISLNINGLTAAYASYLR 2
1 YWPFGQEGCDYHGFQGMISVLASISFMAAIAWDRYHQYCT 1
2 RQKLFWSTSITISLIIWILSILWSAFPLMGWGVYDFEPMRIGCTLDYTKGDR 2
1 DYITYMLSLVFFYLMFPAFIMLSCYDAIYKHFKKIHYYR 0
0 FNTSLPLRVMLMCWGPYVLMCIYACFENVKLVSPKLRM 0
0 LPVIAKTNPFFNALLYSFGNEFYRGGVWNFLTGQKIVEPDVKKSKQK* 0

>RGR2_gadMor Gadus morhua larvae 
0 MAAYALPEGFEEFDMFTFGTALLVG 1
2 GMIGFILNAITIVAYLRVKEMRTPSNFFVFNLALADLSLNINGLTAAYASYAR 2
1 QWPFGQSGCSYHGFQGMISVLASISFMAAISWDRYHQYCT 1
2 KRQKLFWSTTVTMCCIVWVLSVFWAALPLIGWGVYDFEPMRVGCTLDYTIGDR 2
1 NDYITYMLSLVVFYLLFPAYTMMSSYDAINKHFRKIHLQK 0
0 FNTKLPLSVMLACWGPYVLMCVYACFENVKIVSPKLRM 0
0 VLPVLAKTNPISNALLYSFGNESYRSGVWHFLTGQKFVEPSFKKIK*

>RGR2_oncMyk Oncorhynchus mykiss (trout)
0 MAAYTLPEGFSDFDMFAFGSALLVG 1
2 GLLGFFLNAISILAYISVKQMRTPSNFLVFNLAVADIVLNLNGLIAAYASLFYR 2
1 HWPWGQDGCSNHAFMGMTAVLASISFLAAIAWDRYHQYVT 1
2 KNQKLFWSTAWTISIIIWGLAIIWAAVPLIGWGVYDFEPMRTCCTLDYTKGDN 2
1 MDYITYMGALTVFYLIFPAYVMKSNYDAIHAYFKKIHKHR 0
0 WNTSIPLRVLLFCWGPYEIMCIYACFGNARLSPKLRM 0
0 LLPVLRKTNPISNAWLYSFGNEFYRGGVWQFLTGQKFTEPVVVKLKGR*

>RGR2_esoLuc Esox lucius (pike) fragment
0 MAAYTLPEGFSDFDMVAFGSALLVG 1
2 GLAGFFLNATSILAFVSVKQMRTPSNFLVFNLAVADIMLNTSGLIAAYASLSYR 2
1 HWPWGQDGCSNHAFFGMTAVLTSISFLAVIAWDRYHQYVT 1
2 KNQKLFWSTAWTFSIIIWGMAIFWAYVPLTGWGVYDFEPMRTCCTLDY 

>RGR2_hipHip Hippoglossus hippoglossus (halibut) fragment
0 MAAFTLPEGFTDFDMFTFGTALLVG 1
2 GMLGFVLNAISIVSFLTVKEMRNPSNFFVFNLAVADLCLNINGLTAAYASYLR 2
1 YWPFGQDGCSYHGFQGMISVLASISFMAAIAWDRYHQYCT 1
2 KRQKLFWSTTLTMSGIIWILSIFWAAVPLMGWGAYYFEPMKTCCTLDYTRGDR 2
1 DYVTYMLTLV
</pre>
[[Category:Comparative Genomics]]