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.
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 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 RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT RGR_panTro RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT RGR_gorGor RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT RGR_ponPyg RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT RGR_nomLeu RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT RGR_macMul RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT RGR_papHam RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT RGR_calJac RWPYGSDGCQIHGFQGFVTALASICGSAAIAWGRYHHYCT RGR_tarSyr RWPYGLDGCQAHGFQGFVTALASIGGSAAIAWGRYHHYCT RGR_otoGar RWPYGSGGCQAHGFQGFTTALASICGSAAIAWGRYHHYCT RGR_micMur RWPYGSGGCQAHGFQGFTTALASICGSAAIAWGRYHHYCT RGR_tupBel RWPYGSDGCKVHGFQGFATALASISGSAAIAWGRYHQYCT RGR_musMus RWPHGSEGCQVHGFQGFATALASICGSAAVAWGRYHHYCT RGR_ratNor RWPHGSEGCRVHGFQGFATALASICGSAAIAWGRYHHYCT RGR_cavPor HWP-GSGHCQALGFQGFTTALASISGTAALSWGRHQQCCT RGR_dipOrd HWPYGLEGCQAHGFQGFVTALASISGSAAIAWGRCHHHCT RGR_speTri RWPYGSDGCQAHGFQGFVTALSSICGSAAIAWGRYHHYCT RGR_oryCun RWPYGSDGCQAHGFQGFATALASICGSAAIAWGRYHHYCT RGR_ochPri RWPYGSDGCQAHGFQGFATALASICGSAAIAWGRYHHYCT RGR_bosTau RWPYGSEGCQAHGFQGFVTALASICSSAAVAWGRYHHFCT RGR_susScr RWPYGSEGCQAHGFQGFATALASICSSAAIAWGRYHHYCT RGR_turTru RWPYGSDGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT RGR_equCab RWPYGSEGCQAHGFQGFVTALASICSSAAIAWGRYHHYCT RGR_felCat RWPYGSNGCQAHGFQGFVTALASICSSAAIAWGRYHHYCS RGR_eriEur RWPYGSDGCQAHGFQGFVMALASICSSAAIAWGRYHHHCT RGR_myoLuc RWPYGSGGCQAHGFQGFAAALASICGSAAVAWGRYHHYCT RGR_pteVam RWPFGPDGCQAHGFQGFATALASICSSAAIAWGRYHHYCT RGR_canFam RWPYGPDGCQAHGFQGFATALASICSSAALAWGRYHHYCT RGR_sorAra RWPFGPDGCQAHGFQGFATALASICSSAAIAWGRYHHYCT RGR_loxAfr RWPYGSDGCQAHGFQGFVTALASICSCAAIAWERYHHYCT RGR_echTel HWPYGSGGCQAHGFQGFTVALASICSCAAIAWERYHHYCT RGR_proCap RWPYGSDGCQAHGFQGFVMALTSICSCAAIAWERYHHYCT RGR_dasNov RWPYGSGGCQAHGFQGFVTALASISSSAAIAWERCHRHCI RGR_choHof RWPHGSDSCQAHSFQGFATALASISSSAAIAWERYRHHCT RGR_monDom gene lost RGR_macEug gene lost RGR_ornAna HWPYGAEGCRLHGFQGFATALASISLSAAIGWDRYLRHCS RGR_anoCar YWPYGSDGCQIHGFHGFLTALTSISSAAAVAWDRHHQYCT RGR_galGal YWPYGSEGCQIHGFQGFLTALASISSSAAVAWDRYHHYCT RGR_taeGut YWPYGSDGCQIHGFQGFLTALASIGSSAAIAWDRYHHYCT RGR_xenTro YWPYGSEGCQIHGFQGFVAALSSIGSCAAIAWDRYHQYCT RGR_xenLae YWPYGSEGCQIHGFQGFVAALSSIGSCAAIAWDRYHQYCT RGR_danRer YWPYGSDGCQTHGFQGFMTALASIHFIAAIAWDRYHQYCT RGR_pimPro YWPYGSDGCQTHGFQGFMTALASIHFIAAIAWDRYHQYCT RGR_takRub YWPYGSDGCQTHGFQGFVTALASIHFVAAIAWDRYHQYCT RGR_tetNig YWPYGSEGCQTHGFQGFVTALASIHFVAAIAWDRYHQYCT RGR_gasAcu YWPYGSDGCQTHGFQGFVTALASIHFIAAIAWDRYHQYCT RGR_oryLat YWPYGSEGCQTHGFHGFLTALASIHFIAAIAWDRYHQYCT RGR_gadMor YWPYGSDGCQTHGFQGFTVALASIHFVAAIAWDRYHQYCT RGR_poeRet YWPFGQEGCNYHAFQGMISVLASISFMAAIAWDRYHQYCT RGR_osmMor YWPYGSDGCQTHGFQGFMTALASIHFVAAIAWDRYHQYCT RGR_spaAur yWPYGSDGCQTHGFQGFCTALASIHFIAAIAWDRYHQYCT RGR_hipHip YWPFGQDGCSYHGFQGMISVLASISFMAAIAWDRYHQYCT RGR_melAur yWPFGQDGCAYHGFQGMISILASISFLAAIAWDRYHQYCT RGR_calMil YWPYGSEGCQTHGFHGFLMALASINACAAIAWDRYHQNCS
PhyloSNPs in RGR
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.
Loss of RGR in marsupials
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, 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.
Gain of second RGR 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 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 6 other 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.
The two paralogs do not have any indels of phylogenetic significance, though the N- and C-termini have somewhat variable length. 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.
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 heterotrimeric G protein. However from the alignments below, it can be seen that the critical YR portion of the heterotrimeric Galpha binding motif is missing in the GRY mammals.Consequently, with a broken DRY switch and unfavorable distal region, these opsins will not be able to signal through binding to a Galpha protein. Technically, they are no longer 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 Galpha binding 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.
Which of the 16 vertebrate paralogs of Galpha do these 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 Ga 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 from 7-transmembrane fitting.
Alternatively, seeking primary sequence correlations from comparative genomics, requires extensive seeding from experimentally known opsin/Galpha binding pairs as classified in an Oct 2008 cnidarian opsin study. This is not ab initio prediction so much as homology transfer across orthology classes to opsins lacking direct experimental data.
However RGR has only distant sequence and exon boundary affinities to ciliary imaging opsins. One intriguing possibility, given highly significant expression in olfactory node, is Golf (Gs) signaling via type 3 adenylyl cyclase in which elevated cAMP activates CNG membrane conductance channels. Yet the connection between RGR photoreception and olfaction is not at all clear -- the massive loss of olfactory genes in primates has similar timing to the advent of GRY but leaves mouse olfaction uncorrelated.
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 eminate from RPE/choroid or retina, probably because of library bias.
The terminus of RGR aligned from 47 available vertebrate sequences showing GRY ERY and DRY species: GPIFMTIPAFFAKSAAIYNPVIYIMMNKQFRNCMLTTICCGK (rhodopsin) 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 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 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 GPIFMTIPAFFAKSA AIYNPVIY IMMNKQFRNCMLTTICCGK (rhodopsin)
Local splice migration and exon-skipping in RGR opsins
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 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.
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
RGR reference sequences from 51 vertebrates
>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 >RGR_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
RGR2 reference sequences from 5 teleost fish
>RGR2_danRer zebrafish NM_001024436 embryonic RPE, brain, gut, embryo 0 MASYPLPEGFTDFDMFAFGSALLVG 1 2 GLLGFFLNAISVLAFLRVREMQTPNNFFIFNLAVADLSLNINGLVAAYACYLR 2 1 HWPFGSEGCQLHAFQGMVSILAAISFLGAVAWDRYHQYCT 1 2 KQKMFWSTSITISCLIWILAVFWAAMPLPAIGWGVFDFEPLRTCCTLDYSQGDR 2 1 GYITYMLTITVLYLAFPVLVLQSSYSAIHAYFKKTHHYR 0 0 FNTGLPLKALLFCWGPYVVVCSLACFEDVSVLSPRLRMV 0 0 LPVLAKTSPIFHAVLYAYGNEFYRGGVWQFLTGQKSADKKK* 0 >RGR2_tetNig Tetraodon nigroviridis eyes 0 MFTFGTALLVG 1 2 GVLGFFLNAISIVSFLTVKEMRNPSNFFVFNLALADISLNVNGLIAAYASYLR 2 1 YWPFGQDGCSYHAFHGMISVLASISFMAAIAWDRYHQYCT 1 2 RQKLFWSTTLTMSSIIWILSIFWSAVPLMGWGVYDFEPMRTCCTLDYTRGDR 2 1 DYVTYMLTLVVLYLTFPAATMWSCYDSIYKHFKKVHQHR 0 0 FNTSMPLRVLLVCWGPYVVMCVYACFENVKVVSPKLRML 0 0 LPVIAKTNPIFNALLYTFGNEFYRGGVWHFLTGHKIVDPVLKKSK* 0 >RGR2_gasAcu Gasterosteus aculeatus eye 0 MAAFALPEGFTEFDMFTFGSALLVG 1 2 GLIGFFLNAISIASFLRVKEMWNPSNFFVFNLAVADICLNVNGLTAAYASYLR 2 1 YWPFGQDGCTFHAFQGMIAVLASISFMGVIAWDRYHQYCT 1 2 RQKLFWSTTLTMSAIIWILSIFWAAVPLMGWGVYDFEPMRTCCTLDYTKGDR 2 1 DYVTYMLTLVFLYLMFPALTMWSCYDAIHKHFKKIHLHK 0 0 FNTSTPLRVLLMCWGPYVLMCIYACFENVKVVSPKLRMV 0 0 LPVVAkTNPIFNALLYSFGNEFYRGGVWHFLTGQKMVDPVVKKSK* 0 >RGR2_pimPro Pimephales promelas liver brain 0 MASYALPEGFSDFDMFAFGSALLVG 1 2 GLLGFFLNLISVLAFLRVREIQTPNNFFIFNLAVADLSLNINGLVAAYASYLR 2 1 YWPFGSEGCQIHGFQGMVSILASISFLGAIAWDRYHLYCT 1 2 KQKMFWSTSGTISALIWILAVFWAALPLPAIGWGVFDFEPMRTCCTLDYTIGDR 2 1 NYISYMLTITVLYLAFPVLIMQSSYNGIYAHFKKTHHFK 0 0 FNTGLPLKMLLFCWGPYVLMCTYACFENASLVSPKLRMV 0 0 LPVLAKTSPIFHAAMYAYGNEFYRGGIWQFLTGQKPADKKK* 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 FNTSLPLRVMLMCWGPYVLMCIYACFENVKLVSPKLRML 0 0 LPVIAKTNPFFNALLYSFGNEFYRGGVWNFLTGQKIVEPDVKKSKQK* 0
