https://genomewiki.ucsc.edu/index.php?title=Opsin_evolution:_informative_indels&feed=atom&action=historyOpsin evolution: informative indels - Revision history2024-03-28T08:59:40ZRevision history for this page on the wikiMediaWiki 1.38.4https://genomewiki.ucsc.edu/index.php?title=Opsin_evolution:_informative_indels&diff=9790&oldid=prevTomemerald at 16:24, 23 March 20102010-03-23T16:24:48Z<p></p>
<a href="https://genomewiki.ucsc.edu/index.php?title=Opsin_evolution:_informative_indels&diff=9790&oldid=9103">Show changes</a>Tomemeraldhttps://genomewiki.ucsc.edu/index.php?title=Opsin_evolution:_informative_indels&diff=9103&oldid=prevTomemerald: /* Indels in other opsins */2009-12-27T22:52:26Z<p><span dir="auto"><span class="autocomment">Indels in other opsins</span></span></p>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Informative indels would be very helpful in <del style="font-weight: bold; text-decoration: none;">this class </del>of opsins because their sequence relationships to ciliary and melanopsins are too weak. Note [[Opsin_evolution:_ancestral_introns|intron patterns]], another class of even rarer genetic event and so even better suited for deep time scales <del style="font-weight: bold; text-decoration: none;">-- </del>has already illuminated branching relationships to a certain extent.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Informative indels would be very helpful in <ins style="font-weight: bold; text-decoration: none;">the peropsin/neuropsin/rgropsin group </ins>of opsins because their sequence relationships to ciliary and melanopsins are too weak <ins style="font-weight: bold; text-decoration: none;">to determine root topology</ins>. Note [[Opsin_evolution:_ancestral_introns|intron patterns]], another class of even rarer genetic event and so even better suited for deep time scales<ins style="font-weight: bold; text-decoration: none;">, </ins>has already illuminated branching relationships to a certain extent.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>(to be continued) </div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>(to be continued) </div></td></tr>
</table>Tomemeraldhttps://genomewiki.ucsc.edu/index.php?title=Opsin_evolution:_informative_indels&diff=9086&oldid=prevTomemerald at 16:31, 27 December 20092009-12-27T16:31:11Z<p></p>
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<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">'''See also:''' [[Opsin_evolution|Curated Sequences]] | [[Opsin_evolution:_ancestral_introns|Ancestral Introns]] | [[Opsin_evolution:_Cytoplasmic_face|Cytoplasmic face]] | [[Opsin_evolution:_ancestral_sequences|Ancestral Sequences]] | [[Opsin_evolution:_alignment|Alignment]] | [[Opsin_evolution:_update_blog|Update Blog]]</ins></div></td></tr>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=== Introduction to indels ===</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=== Introduction to indels ===</div></td></tr>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>(to be continued) </div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>(to be continued) </div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"></ins></div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">'''See also:''' [[Opsin_evolution|Curated Sequences]] | [[Opsin_evolution:_ancestral_introns|Ancestral Introns]] | [[Opsin_evolution:_Cytoplasmic_face|Cytoplasmic face]] | [[Opsin_evolution:_ancestral_sequences|Ancestral Sequences]] | [[Opsin_evolution:_alignment|Alignment]] | [[Opsin_evolution:_update_blog|Update Blog]]</ins></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Category:Comparative Genomics]]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Category:Comparative Genomics]]</div></td></tr>
</table>Tomemeraldhttps://genomewiki.ucsc.edu/index.php?title=Opsin_evolution:_informative_indels&diff=9051&oldid=prevTomemerald: /* Indels in the TM4-EC2-TM5 region */2009-12-26T16:00:04Z<p><span dir="auto"><span class="autocomment">Indels in the TM4-EC2-TM5 region</span></span></p>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>However more than the disulfide and membrane boundaries are important here for this twisted β-hairpin. Almost all opsins are further distinguished by four other conserved residues Y..E.....C..DY (in rhodopsin numbering Y178 E181 C187 D190 Y191) which presumably play the same role in both determined opsin structures. The conservation of the final tyrosine (often tryptophan) persists into GPCR such as tachykinin receptor with highest overall opsin blast scores, though it is not sufficiently universal to occur in the other three structurally determined GPCR. </div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>However more than the disulfide and membrane boundaries are important here for this twisted β-hairpin. Almost all opsins are further distinguished by four other conserved residues Y..E.....C..DY (in rhodopsin numbering Y178 E181 C187 D190 Y191) which presumably play the same role in both determined opsin structures. The conservation of the final tyrosine (often tryptophan) persists into GPCR such as tachykinin receptor with highest overall opsin blast scores, though it is not sufficiently universal to occur in the other three structurally determined GPCR. </div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Various studies pertain to the phenomenonal conservation of these four non-cysteine loop residues. First, interactions with other proteins can be eliminated as these take place on the cytoplasmic side. Proper folding of newly synthesized opsin is a [http://pubs.acs.org/doi/abs/10.1021/ct900145u valid consideration].Y191 is [http://www3.interscience.wiley.com/journal/118586931/abstract proximal to the 9-methyl group] of 11-cis retinal in the dark state; Y191A changes hydrolysis of the Schiff base, folded structure after photobleaching and chkromophore release. R177 [http://www.jbc.org/content/278/19/16982.full forms an ion pair] with D190 but comparative genomics quickly shows this has narrow applicability. </div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Various studies pertain to the phenomenonal conservation of these four non-cysteine loop residues. First, interactions with other proteins can be eliminated as these take place on the cytoplasmic side. Proper folding of newly synthesized opsin is a [http://pubs.acs.org/doi/abs/10.1021/ct900145u valid consideration]. Y191 is [http://www3.interscience.wiley.com/journal/118586931/abstract proximal to the 9-methyl group] of 11-cis retinal in the dark state; Y191A changes hydrolysis of the Schiff base, folded structure after photobleaching and chkromophore release. R177 [http://www.jbc.org/content/278/19/16982.full forms an ion pair] with D190 but comparative genomics quickly shows this has narrow applicability. </div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>E181 has been [http://www.ncbi.nlm.nih.gov/pubmed/12835420 interpreted as the counterion] in Meta I rhodopsin (displacing E113 in the dark state); the reorganization of EC2 then propagates to TM3 via a push from the disulfide. Yet it's hard to see how this could work universally because in LWS the residue is invariably histidine and in VAOP where it is always serine (as SK covarying anomaly). These residues lack the negative charge to offset the Schiff lysine. D and E are also found sporadically in non-opsin GPCR where counterion makes no apparent sense -- this could be pursued in the structure of ADRB1.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>E181 has been [http://www.ncbi.nlm.nih.gov/pubmed/12835420 interpreted as the counterion] in Meta I rhodopsin (displacing E113 in the dark state); the reorganization of EC2 then propagates to TM3 via a push from the disulfide. Yet it's hard to see how this could work universally because in LWS the residue is invariably histidine and in VAOP where it is always serine (as SK covarying anomaly). These residues lack the negative charge to offset the Schiff lysine. D and E are also found sporadically in non-opsin GPCR where counterion makes no apparent sense -- this could be pursued in the structure of ADRB1.</div></td></tr>
</table>Tomemeraldhttps://genomewiki.ucsc.edu/index.php?title=Opsin_evolution:_informative_indels&diff=9049&oldid=prevTomemerald: /* Indels in EC2 region */2009-12-26T15:40:03Z<p><span dir="auto"><span class="autocomment">Indels in EC2 region</span></span></p>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> NPY2R_homS G N SLVIHVVIKFKSMRTVTNFFIANLAVA D LLVN-TLCL P FTLTYTLM-- GEWKMGP VL C P.59.2</font></div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> NPY2R_homS G N SLVIHVVIKFKSMRTVTNFFIANLAVA D LLVN-TLCL P FTLTYTLM-- GEWKMGP VL C P.59.2</font></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>=== Indels in EC2 region ===</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>=== Indels in <ins style="font-weight: bold; text-decoration: none;">the TM4-</ins>EC2<ins style="font-weight: bold; text-decoration: none;">-TM5 </ins>region ===</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;">This </del>region contains the second half of the extracellular disulfide bond which is very important to the overall [http://www.pnas.org/content/101/19/7246.long structural stability] of the GPCR molecule. After years of back and forth, it was eventually [http://www.pnas.org/content/101/19/7246.long concluded] that 92% of gene family members, including all opsin though not all GPCR do contain a disulfide linking extracellular domain <del style="font-weight: bold; text-decoration: none;">EC3 </del>to TM3. </div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">The retinal plug loop </ins>region <ins style="font-weight: bold; text-decoration: none;">EC2 </ins>contains the second half of the extracellular disulfide bond which is very important to the overall [http://www.pnas.org/content/101/19/7246.long structural stability] of the GPCR molecule. After years of back and forth, it was eventually [http://www.pnas.org/content/101/19/7246.long concluded] that 92% of gene family members, including all opsin though not all GPCR do contain a disulfide linking extracellular domain <ins style="font-weight: bold; text-decoration: none;">EC2 </ins>to TM3. </div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:OpsinStability.jpg|left]]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:OpsinStability.jpg|left]]</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>That requires more than just comparative genomic conservation of the two cysteines because overall conservation can be quite high. Furthermore, it is quite difficult to establish homological correspondences in <del style="font-weight: bold; text-decoration: none;">EC3 </del>because of gapping issues (see alignment below). However non-existence or non-conservation of the cysteine does establishe absence. All of the opsin outgroup GPCR considered here do contain a disulfide. The disulfide thus is not at all diagnostic for opsin-class GPCR and its absence reliably implies sequencing error.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>That requires more than just comparative genomic conservation of the two cysteines because overall conservation can be quite high. Furthermore, it is quite difficult to establish homological correspondences in <ins style="font-weight: bold; text-decoration: none;">EC2 </ins>because of gapping issues (see alignment below). However non-existence or non-conservation of the cysteine does establishe absence. All of the opsin outgroup GPCR considered here do contain a disulfide. The disulfide thus is not at all diagnostic for opsin-class GPCR and its absence reliably implies sequencing error.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>These <del style="font-weight: bold; text-decoration: none;">region </del>can only be aligned after careful determination of anchor residues on both sides of the disulfide cysteine. Some are subtle, involving small reduced alphabets of similar residues and imperfect invariance rather than absolute conservation. The anchors consist of a universally conserved W in <del style="font-weight: bold; text-decoration: none;">TM2</del>, a proline prior to TM4 exiting the membrane, the GWS.Y..E region unique to opsins, an aromatic residue 3 residues after the C, and finally the reliable P......CY region well within TM5.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>These <ins style="font-weight: bold; text-decoration: none;">regions </ins>can only be aligned after careful determination of anchor residues on both sides of the disulfide cysteine. Some are subtle, involving small reduced alphabets of similar residues and imperfect invariance rather than absolute conservation. The anchors consist of a universally conserved W in <ins style="font-weight: bold; text-decoration: none;">TM4</ins>, a proline prior to TM4 exiting the membrane, the GWS.Y..E region unique to opsins, an aromatic residue 3 residues after the C, and finally the reliable P......CY region well within TM5.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>This region has been quite permissive with regards to indels over evolutionary time. To account for observed length variations, six indels are needed within opsins and dozens more for the full spectrum of rhodopsin-class GPCR. Unsurprisingly almost all of these can be assigned to the <del style="font-weight: bold; text-decoration: none;">EC3 </del>extracellular loop rather than to TM4 or TM5. Somehow the disulfide bond has been able to accommodate these abrupt length variations without loss of steric capacity for formation, suggesting the loop is otherwise weakly constrained.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>This region has been quite permissive with regards to indels over evolutionary time. To account for observed length variations, six indels are needed within opsins and dozens more for the full spectrum of rhodopsin-class GPCR. Unsurprisingly almost all of these can be assigned to the <ins style="font-weight: bold; text-decoration: none;">EC2 </ins>extracellular loop rather than to TM4 or TM5. Somehow the disulfide bond has been able to accommodate these abrupt length variations without loss of steric capacity for formation, suggesting the loop is otherwise weakly constrained.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>However more than the disulfide and membrane boundaries are important here. Almost all opsins are further distinguished by four other conserved residues Y..E.....C..DY (in rhodopsin numbering Y178 E181 C187 D190 Y191) which presumably play the same role in <del style="font-weight: bold; text-decoration: none;">the two </del>determined opsin structures. The conservation of the final tyrosine (often tryptophan) persists into GPCR such as tachykinin receptor with highest overall opsin blast scores, though it is not sufficiently universal to occur in the other three structurally determined GPCR. <del style="font-weight: bold; text-decoration: none;">No explanation has been provided </del>to <del style="font-weight: bold; text-decoration: none;">date for </del>the phenomenonal conservation of these <del style="font-weight: bold; text-decoration: none;">other 4 </del>loop residues. <del style="font-weight: bold; text-decoration: none;">Interactions </del>with other proteins can be eliminated as these take place on the cytoplasmic side.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>However more than the disulfide and membrane boundaries are important here <ins style="font-weight: bold; text-decoration: none;">for this twisted β-hairpin</ins>. Almost all opsins are further distinguished by four other conserved residues Y..E.....C..DY (in rhodopsin numbering Y178 E181 C187 D190 Y191) which presumably play the same role in <ins style="font-weight: bold; text-decoration: none;">both </ins>determined opsin structures. The conservation of the final tyrosine (often tryptophan) persists into GPCR such as tachykinin receptor with highest overall opsin blast scores, though it is not sufficiently universal to occur in the other three structurally determined GPCR. </div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">Various studies pertain </ins>to the phenomenonal conservation of these <ins style="font-weight: bold; text-decoration: none;">four non-cysteine </ins>loop residues. <ins style="font-weight: bold; text-decoration: none;">First, interactions </ins>with other proteins can be eliminated as these take place on the cytoplasmic side<ins style="font-weight: bold; text-decoration: none;">. Proper folding of newly synthesized opsin is a [http://pubs.acs.org/doi/abs/10.1021/ct900145u valid consideration].Y191 is [http://www3.interscience.wiley.com/journal/118586931/abstract proximal to the 9-methyl group] of 11-cis retinal in the dark state; Y191A changes hydrolysis of the Schiff base, folded structure after photobleaching and chkromophore release. R177 [http://www.jbc.org/content/278/19/16982.full forms an ion pair] with D190 but comparative genomics quickly shows this has narrow applicability. </ins></div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">E181 has been [http://www.ncbi.nlm.nih.gov/pubmed/12835420 interpreted as the counterion] in Meta I rhodopsin (displacing E113 in the dark state); the reorganization of EC2 then propagates to TM3 via a push from the disulfide. Yet it's hard to see how this could work universally because in LWS the residue is invariably histidine and in VAOP where it is always serine (as SK covarying anomaly). These residues lack the negative charge to offset the Schiff lysine. D and E are also found sporadically in non-opsin GPCR where counterion makes no apparent sense -- this could be pursued in the structure of ADRB1</ins>.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Almost all of the indels resolve to insertions despite their relative rarity compared to deletions proteomewide. These insertions evidently arose from some other mechanism than extension of splice donors or acceptors (indicated below by underlining) because the site of insertion is elsewhere, even allowing for gap uncertainties. If some sequence microstructure predisposed certain regions to insertions, little of that may remain 500 myr later. All the key devlopements in ciliary imaging opsins took place prior to lamprey divergence.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Almost all of the indels resolve to insertions despite their relative rarity compared to deletions proteomewide. These insertions evidently arose from some other mechanism than extension of splice donors or acceptors (indicated below by underlining) because the site of insertion is elsewhere, even allowing for gap uncertainties. If some sequence microstructure predisposed certain regions to insertions, little of that may remain 500 myr later. All the key devlopements in ciliary imaging opsins took place prior to lamprey divergence.</div></td></tr>
</table>Tomemeraldhttps://genomewiki.ucsc.edu/index.php?title=Opsin_evolution:_informative_indels&diff=9048&oldid=prevTomemerald: /* Indels in EC2 region */2009-12-26T13:55:49Z<p><span dir="auto"><span class="autocomment">Indels in EC2 region</span></span></p>
<table style="background-color: #fff; color: #202122;" data-mw="interface">
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">← Older revision</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 13:55, 26 December 2009</td>
</tr><tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l612">Line 612:</td>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>This region has been quite permissive with regards to indels over evolutionary time. To account for observed length variations, six indels are needed within opsins and dozens more for the full spectrum of rhodopsin-class GPCR. Unsurprisingly almost all of these can be assigned to the EC3 extracellular loop rather than to TM4 or TM5. Somehow the disulfide bond has been able to accommodate these abrupt length variations without loss of steric capacity for formation, suggesting the loop is otherwise weakly constrained.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>This region has been quite permissive with regards to indels over evolutionary time. To account for observed length variations, six indels are needed within opsins and dozens more for the full spectrum of rhodopsin-class GPCR. Unsurprisingly almost all of these can be assigned to the EC3 extracellular loop rather than to TM4 or TM5. Somehow the disulfide bond has been able to accommodate these abrupt length variations without loss of steric capacity for formation, suggesting the loop is otherwise weakly constrained.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>However more than the disulfide and membrane boundaries are important here. Almost all opsins are further distinguished by four other conserved residues Y..E.....C..DY <del style="font-weight: bold; text-decoration: none;">about </del>C187 which presumably play the same role in the two determined opsin structures. The conservation of the final tyrosine (often tryptophan) persists into GPCR such as tachykinin receptor with highest overall opsin blast scores, though it is not sufficiently universal to occur in the other three structurally determined GPCR. No explanation has been provided to date for the phenomenonal conservation of these other 4 loop residues. Interactions with other proteins can be eliminated as these take place on the cytoplasmic side.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>However more than the disulfide and membrane boundaries are important here. Almost all opsins are further distinguished by four other conserved residues Y..E.....C..DY <ins style="font-weight: bold; text-decoration: none;">(in rhodopsin numbering Y178 E181 </ins>C187 <ins style="font-weight: bold; text-decoration: none;">D190 Y191) </ins>which presumably play the same role in the two determined opsin structures. The conservation of the final tyrosine (often tryptophan) persists into GPCR such as tachykinin receptor with highest overall opsin blast scores, though it is not sufficiently universal to occur in the other three structurally determined GPCR. No explanation has been provided to date for the phenomenonal conservation of these other 4 loop residues. Interactions with other proteins can be eliminated as these take place on the cytoplasmic side.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Almost all of the indels resolve to insertions despite their relative rarity compared to deletions proteomewide. These insertions arose from some other mechanism than extension of splice donors or acceptors (indicated below by <del style="font-weight: bold; text-decoration: none;">discordant </del>underlining). <del style="font-weight: bold; text-decoration: none;">This suggests </del>a structurally determined floor to admissible loop lengths. After discounting derived forms, all opsin classes other than neuropsins have the same minimal length, including cnidarian and ctenophore opsins. Thus the ancestral opsin likely had this length and pattern:</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Almost all of the indels resolve to insertions despite their relative rarity compared to deletions proteomewide. These insertions <ins style="font-weight: bold; text-decoration: none;">evidently </ins>arose from some other mechanism than extension of splice donors or acceptors (indicated below by underlining) <ins style="font-weight: bold; text-decoration: none;">because the site of insertion is elsewhere, even allowing for gap uncertainties. If some sequence microstructure predisposed certain regions to insertions, little of that may remain 500 myr later</ins>. <ins style="font-weight: bold; text-decoration: none;">All the key devlopements in ciliary imaging opsins took place prior to lamprey divergence.</ins></div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">Overall, the pattern of insertions but not deletions suggest </ins>a structurally determined floor to admissible loop lengths. After discounting derived forms, all opsin classes other than neuropsins have the same minimal length, including cnidarian and ctenophore opsins. Thus the ancestral opsin likely had this length and pattern:</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <font color="blue">W.........P..GW</font><font color="brown">S.Y..E.....C..DW........SY</font><font color="blue">...........P.......Y</font></div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <font color="blue">W.........P..GW</font><font color="brown">S.Y..E.....C..DW........SY</font><font color="blue">...........P.......Y</font></div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"></ins></div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">These region provides various synapamorphies for opsin classes. Each of these is represented by a single proxy sequence that accurately represents its ortholog class. For example, all UV7 arthopod opsins have the same two residue insertion at the end of TM4, not just the Rhodnius prolixis representative shown. Homoplasy can be seen in some instances (eg the five imaging cilopsins and the four dimly related neuropsins both have two extra residues following Y191) but it remains managable when it occurs in two well-separated regions of what is a very deep and comprehensive gene tree. </ins></div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"></ins></div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"></ins></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:OpsinEC3indels.png|left]]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:OpsinEC3indels.png|left]]</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br clear="all"></div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br clear="all"></div></td></tr>
</table>Tomemeraldhttps://genomewiki.ucsc.edu/index.php?title=Opsin_evolution:_informative_indels&diff=9047&oldid=prevTomemerald: /* Indels in EC2 region */2009-12-26T12:07:53Z<p><span dir="auto"><span class="autocomment">Indels in EC2 region</span></span></p>
<table style="background-color: #fff; color: #202122;" data-mw="interface">
<col class="diff-marker" />
<col class="diff-content" />
<col class="diff-marker" />
<col class="diff-content" />
<tr class="diff-title" lang="en">
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">← Older revision</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 12:07, 26 December 2009</td>
</tr><tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l610">Line 610:</td>
<td colspan="2" class="diff-lineno">Line 610:</td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>These region can only be aligned after careful determination of anchor residues on both sides of the disulfide cysteine. Some are subtle, involving small reduced alphabets of similar residues and imperfect invariance rather than absolute conservation. The anchors consist of a universally conserved W in TM2, a proline prior to TM4 exiting the membrane, the GWS.Y..E region unique to opsins, an aromatic residue 3 residues after the C, and finally the reliable P......CY region well within TM5.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>These region can only be aligned after careful determination of anchor residues on both sides of the disulfide cysteine. Some are subtle, involving small reduced alphabets of similar residues and imperfect invariance rather than absolute conservation. The anchors consist of a universally conserved W in TM2, a proline prior to TM4 exiting the membrane, the GWS.Y..E region unique to opsins, an aromatic residue 3 residues after the C, and finally the reliable P......CY region well within TM5.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>This region has been quite permissive with regards to indels over evolutionary time. To account for observed length variations, six indels are needed within opsins and dozens more for the full spectrum of rhodopsin-class GPCR. Unsurprisingly<del style="font-weight: bold; text-decoration: none;">, </del>almost all of these can be assigned to the EC3 extracellular loop rather than to TM4 or TM5. Somehow the disulfide bond has been able to accommodate these abrupt length variations without loss of steric formation <del style="font-weight: bold; text-decoration: none;">capacity</del>, suggesting the loop is otherwise weakly constrained.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>This region has been quite permissive with regards to indels over evolutionary time. To account for observed length variations, six indels are needed within opsins and dozens more for the full spectrum of rhodopsin-class GPCR. Unsurprisingly almost all of these can be assigned to the EC3 extracellular loop rather than to TM4 or TM5. Somehow the disulfide bond has been able to accommodate these abrupt length variations without loss of steric <ins style="font-weight: bold; text-decoration: none;">capacity for </ins>formation, suggesting the loop is otherwise weakly constrained.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>However more than the disulfide and membrane <del style="font-weight: bold; text-decoration: none;">junctions </del>are important here. Almost all opsins are further distinguished by <del style="font-weight: bold; text-decoration: none;">two following </del>conserved residues C..<del style="font-weight: bold; text-decoration: none;">DW </del>which presumably <del style="font-weight: bold; text-decoration: none;">make </del>the same <del style="font-weight: bold; text-decoration: none;">structural contribution </del>in the two opsin <del style="font-weight: bold; text-decoration: none;">crystallographic determinations</del>. <del style="font-weight: bold; text-decoration: none;">This </del>conservation persists into <del style="font-weight: bold; text-decoration: none;">certain </del>GPCR such as tachykinin receptor with highest overall blast scores <del style="font-weight: bold; text-decoration: none;">to opsins</del>, though it is not sufficiently universal to <del style="font-weight: bold; text-decoration: none;">carry over to </del>the other structurally determined GPCR.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>However more than the disulfide and membrane <ins style="font-weight: bold; text-decoration: none;">boundaries </ins>are important here. Almost all opsins are further distinguished by <ins style="font-weight: bold; text-decoration: none;">four other </ins>conserved residues <ins style="font-weight: bold; text-decoration: none;">Y..E.....</ins>C..<ins style="font-weight: bold; text-decoration: none;">DY about C187 </ins>which presumably <ins style="font-weight: bold; text-decoration: none;">play </ins>the same <ins style="font-weight: bold; text-decoration: none;">role </ins>in the two <ins style="font-weight: bold; text-decoration: none;">determined </ins>opsin <ins style="font-weight: bold; text-decoration: none;">structures</ins>. <ins style="font-weight: bold; text-decoration: none;">The </ins>conservation <ins style="font-weight: bold; text-decoration: none;">of the final tyrosine (often tryptophan) </ins>persists into GPCR <ins style="font-weight: bold; text-decoration: none;"> </ins>such as tachykinin receptor with highest overall <ins style="font-weight: bold; text-decoration: none;">opsin </ins>blast scores, though it is not sufficiently universal to <ins style="font-weight: bold; text-decoration: none;">occur in </ins>the other <ins style="font-weight: bold; text-decoration: none;">three </ins>structurally determined GPCR<ins style="font-weight: bold; text-decoration: none;">. No explanation has been provided to date for the phenomenonal conservation of these other 4 loop residues. Interactions with other proteins can be eliminated as these take place on the cytoplasmic side</ins>.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Almost all of the indels resolve to insertions despite their relative rarity compared to deletions proteomewide. These insertions arose from some other mechanism than extension of splice donors or acceptors (indicated below by discordant underlining). This suggests a <del style="font-weight: bold; text-decoration: none;">stucturally </del>determined floor to admissible loop lengths. After discounting derived forms, all opsin classes other than neuropsins have the same minimal length, including cnidarian and ctenophore opsins. Thus the ancestral opsin likely had this length and pattern:</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Almost all of the indels resolve to insertions despite their relative rarity compared to deletions proteomewide. These insertions arose from some other mechanism than extension of splice donors or acceptors (indicated below by discordant underlining). This suggests a <ins style="font-weight: bold; text-decoration: none;">structurally </ins>determined floor to admissible loop lengths. After discounting derived forms, all opsin classes other than neuropsins have the same minimal length, including cnidarian and ctenophore opsins. Thus the ancestral opsin likely had this length and pattern:</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <font color="blue">W.........P..GW</font><font color="brown">S.Y..E.....C..DW........SY</font><font color="blue">...........P.......Y</font></div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <font color="blue">W.........P..GW</font><font color="brown">S.Y..E.....C..DW........SY</font><font color="blue">...........P.......Y</font></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:OpsinEC3indels.png|left]]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:OpsinEC3indels.png|left]]</div></td></tr>
</table>Tomemeraldhttps://genomewiki.ucsc.edu/index.php?title=Opsin_evolution:_informative_indels&diff=9044&oldid=prevTomemerald: /* Indels in EC2 region */2009-12-26T11:47:55Z<p><span dir="auto"><span class="autocomment">Indels in EC2 region</span></span></p>
<table style="background-color: #fff; color: #202122;" data-mw="interface">
<col class="diff-marker" />
<col class="diff-content" />
<col class="diff-marker" />
<col class="diff-content" />
<tr class="diff-title" lang="en">
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">← Older revision</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 11:47, 26 December 2009</td>
</tr><tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l615">Line 615:</td>
<td colspan="2" class="diff-lineno">Line 615:</td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Almost all of the indels resolve to insertions despite their relative rarity compared to deletions proteomewide. These insertions arose from some other mechanism than extension of splice donors or acceptors (indicated below by discordant underlining). This suggests a stucturally determined floor to admissible loop lengths. After discounting derived forms, all opsin classes other than neuropsins have the same minimal length, including cnidarian and ctenophore opsins. Thus the ancestral opsin likely had this length and pattern:</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Almost all of the indels resolve to insertions despite their relative rarity compared to deletions proteomewide. These insertions arose from some other mechanism than extension of splice donors or acceptors (indicated below by discordant underlining). This suggests a stucturally determined floor to admissible loop lengths. After discounting derived forms, all opsin classes other than neuropsins have the same minimal length, including cnidarian and ctenophore opsins. Thus the ancestral opsin likely had this length and pattern:</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;"><br clear="all"></del></div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <font color="blue">W.........P..GW</font><font color="brown">S.Y..E.....C..DW........SY</font><font color="blue">...........P.......Y</font></div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <del style="font-weight: bold; text-decoration: none;">Ancestral opsin: </del><font color="blue">W.........P..GW</font><font color="brown">S.Y..E.....C..DW........SY</font><font color="blue">...........P.......Y</font></div></td><td colspan="2" class="diff-side-added"></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:OpsinEC3indels.png|left]]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:OpsinEC3indels.png|left]]</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br clear="all"></div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br clear="all"></div></td></tr>
</table>Tomemeraldhttps://genomewiki.ucsc.edu/index.php?title=Opsin_evolution:_informative_indels&diff=9043&oldid=prevTomemerald: /* Indels in EC2 region */2009-12-26T11:45:46Z<p><span dir="auto"><span class="autocomment">Indels in EC2 region</span></span></p>
<table style="background-color: #fff; color: #202122;" data-mw="interface">
<col class="diff-marker" />
<col class="diff-content" />
<col class="diff-marker" />
<col class="diff-content" />
<tr class="diff-title" lang="en">
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">← Older revision</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 11:45, 26 December 2009</td>
</tr><tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l617">Line 617:</td>
<td colspan="2" class="diff-lineno">Line 617:</td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br clear="all"></div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><br clear="all"></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> Ancestral opsin: <font color="blue">W.........P..GW</font><font color="brown">S.Y..E.....C..DW........SY</font><font color="blue">...........P.......Y</font></div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> Ancestral opsin: <font color="blue">W.........P..GW</font><font color="brown">S.Y..E.....C..DW........SY</font><font color="blue">...........P.......Y</font></div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;"></del></div></td><td colspan="2" class="diff-side-added"></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;"></del></div></td><td colspan="2" class="diff-side-added"></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:OpsinEC3indels.png|left]]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:OpsinEC3indels.png|left]]</div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"><br clear="all"></ins></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=== Indels in other opsins ===</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=== Indels in other opsins ===</div></td></tr>
</table>Tomemeraldhttps://genomewiki.ucsc.edu/index.php?title=Opsin_evolution:_informative_indels&diff=9041&oldid=prevTomemerald: /* Indels in EC2 region */2009-12-26T11:41:47Z<p><span dir="auto"><span class="autocomment">Indels in EC2 region</span></span></p>
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 11:41, 26 December 2009</td>
</tr><tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l602">Line 602:</td>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=== Indels in EC2 region ===</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>=== Indels in EC2 region ===</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>This region contains the second half of the extracellular disulfide bond which is very important to the overall structural stability of the GPCR molecule. After years of back and forth, it was eventually [http://www.pnas.org/content/101/19/7246.long concluded] that 92% of gene family members, including all opsin though not all GPCR do contain a disulfide linking extracellular domain EC3 to TM3. </div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>This region contains the second half of the extracellular disulfide bond which is very important to the overall <ins style="font-weight: bold; text-decoration: none;">[http://www.pnas.org/content/101/19/7246.long </ins>structural stability<ins style="font-weight: bold; text-decoration: none;">] </ins>of the GPCR molecule. After years of back and forth, it was eventually [http://www.pnas.org/content/101/19/7246.long concluded] that 92% of gene family members, including all opsin though not all GPCR do contain a disulfide linking extracellular domain EC3 to TM3. </div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td colspan="2" class="diff-side-deleted"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">[[Image:OpsinStability.jpg|left]]</ins></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>That requires more than just comparative genomic conservation of the two cysteines because overall conservation can be quite high. Furthermore, it is quite difficult to establish homological correspondences in EC3 because of gapping issues (see alignment below). However non-existence or non-conservation of the cysteine does establishe absence. All of the opsin outgroup GPCR considered here do contain a disulfide. The disulfide thus is not at all diagnostic for opsin-class GPCR and its absence reliably implies sequencing error.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>That requires more than just comparative genomic conservation of the two cysteines because overall conservation can be quite high. Furthermore, it is quite difficult to establish homological correspondences in EC3 because of gapping issues (see alignment below). However non-existence or non-conservation of the cysteine does establishe absence. All of the opsin outgroup GPCR considered here do contain a disulfide. The disulfide thus is not at all diagnostic for opsin-class GPCR and its absence reliably implies sequencing error.</div></td></tr>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Almost all of the indels resolve to insertions despite their relative rarity compared to deletions proteomewide. These insertions arose from some other mechanism than extension of splice donors or acceptors (indicated below by discordant underlining). This suggests a stucturally determined floor to admissible loop lengths. After discounting derived forms, all opsin classes other than neuropsins have the same minimal length, including cnidarian and ctenophore opsins. Thus the ancestral opsin likely had this length and pattern:</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Almost all of the indels resolve to insertions despite their relative rarity compared to deletions proteomewide. These insertions arose from some other mechanism than extension of splice donors or acceptors (indicated below by discordant underlining). This suggests a stucturally determined floor to admissible loop lengths. After discounting derived forms, all opsin classes other than neuropsins have the same minimal length, including cnidarian and ctenophore opsins. Thus the ancestral opsin likely had this length and pattern:</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> </div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"><br clear="all"></ins></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> Ancestral opsin: <font color="blue">W.........P..GW</font><font color="brown">S.Y..E.....C..DW........SY</font><font color="blue">...........P.......Y</font></div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> Ancestral opsin: <font color="blue">W.........P..GW</font><font color="brown">S.Y..E.....C..DW........SY</font><font color="blue">...........P.......Y</font></div></td></tr>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>[[Image:OpsinEC3indels.png]]</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>[[Image:OpsinEC3indels.png<ins style="font-weight: bold; text-decoration: none;">|left</ins>]]</div></td></tr>
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</table>Tomemerald