Coding indels: PRNP: Difference between revisions

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Consequently this data set strongly conflicts with the never-ending computer proposals placing mouse basal relative to dog and human, ie (mouse,(dog,human)), which would require both a global revision of the well-established super-ordinal mammalian tree and in PRNP highly non-parsimonious multiple events both bizarrely located basally at the two unrelated divergence stems (very dense phylogenetic sampling has the effect of squeezing the window on homoplasy).  
Consequently this data set strongly conflicts with the never-ending computer proposals placing mouse basal relative to dog and human, ie (mouse,(dog,human)), which would require both a global revision of the well-established super-ordinal mammalian tree and in PRNP highly non-parsimonious multiple events both bizarrely located basally at the two unrelated divergence stems (very dense phylogenetic sampling has the effect of squeezing the window on homoplasy).  


Signal region indels are not especially rare among orthologs to the [http://proline.bic.nus.edu.sg/spdb/index.html 4500-odd human genes with signal peptides] of which 595 are experimentally validated, despite steric requirements of the binding pocket of the signal processing complex SRP. In actuality the distribution of signal peptide length is fairly broad. These indels can be rapidly screened in batches of 25 by [http://genome-test.cse.ucsc.edu/cgi-bin/hgBlat Blat] alignment relative to the 44 available vertebrate genomes.
Signal region indels are not especially rare among orthologs to the [http://proline.bic.nus.edu.sg/spdb/index.html 4500-odd human genes with signal peptides] of which 595 are experimentally validated, despite steric requirements of the binding pocket of the signal processing complex SRP. In actuality the distribution of signal peptide length is fairly broad. These indels can be rapidly screened in batches of 25 by [http://genome-test.gi.ucsc.edu/cgi-bin/hgBlat Blat] alignment relative to the 44 available vertebrate genomes.


However few of these indels have any phylogenetic depth. It does not appear that the PRNP indel in euarchontoglires has any significant effect on cell targeting by the signal peptide (or subsequent membrane topology). It is not that indels in signal peptides are so rare but rather narrowly windowed basal events in large clades.
However few of these indels have any phylogenetic depth. It does not appear that the PRNP indel in euarchontoglires has any significant effect on cell targeting by the signal peptide (or subsequent membrane topology). It is not that indels in signal peptides are so rare but rather narrowly windowed basal events in large clades.


Below is data from 96 species:
Below is data from 112 species:


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MA--NLGCWMLVLFVATWSDLGLCKKRPKPG    Presbytis francoisi
MA--NLGCWMLVLFVATWSDLGLCKKRPKPG    Presbytis francoisi
MA--NLGCWMLVLFVATWSDLGLCKKRPKPG    Saimiri sciureus
MA--NLGCWMLVLFVATWSDLGLCKKRPKPG    Saimiri sciureus
ME--NLGCWMLILFVATWSDIGLCKKRPKPG    Galeopterus variegatus
MA--KLGYWLLVLFVATWSDVGLCKKRPKPG    Tarsius syrichta
MA--KLGYWLLVLFVATWSDVGLCKKRPKPG    Tarsius syrichta
MA--NLGCWMLVVFVATWSDVGLCKKRPKPG    Microcebus murinus
MA--NLGCWMLVVFVATWSDVGLCKKRPKPG    Microcebus murinus
Line 87: Line 88:
MVKNYIGGWILVLFVATWSDVGLCKKRPKPG    Pteropus vampyrus
MVKNYIGGWILVLFVATWSDVGLCKKRPKPG    Pteropus vampyrus
MVKSHIANWILVLFVATWSDMGFCKKRPKPG    Tursiops truncatus
MVKSHIANWILVLFVATWSDMGFCKKRPKPG    Tursiops truncatus
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG    Felis catus
MVKGHIGGWILVLFVATWSDVGLCKKRPKPG    Panthera leo
MVKGHIGGWILVLFVATWSDVGLCKKRPKPG    Puma concolor
MVKGHIGGWILVLFVATWSDVGLCKKRPKPG    Neofelis nebulosa
MVKGHIGGWILVLFVATWSDVGLCKKRPKPG    Lynx canadensis
MVKGHIGGWILVLFVATWSDVGLCKKRPKPG    Lynx rufus
MVKGHIGGWILVLFVATWSDVGLCKKRPKPG    Acinonyx jubatus
MVKSHIGGWILLLFVATWSDVGLCKKRPKPG    Vulpes vulpes
MVKSHIGGWILLLFVATWSDVGLCKKRPKPG    Vulpes lagopus
MVKSHIGSWLLVLFVATWSDIGFCKKWPKPG    Neovison vison
MVKSHIGGWILVLFVATWSDVGLCKKRPKPG    Ursus americanus
MVKSHIGGWILVLFVAAWSDVGLCKKRPKPG    Phoca vitulina
MVKSHIGSWILVLFVATWSDVGLCKKRPKPG    Odobenus rosmarus
MVGSHIGGWILILFVATWSDVGLCKKRPKPG    Mephitis mephitis
MVKSHIGSWLLVLFVATWSDIGFCKKRPKPG    Gulo gulo
MMKSHVGGWILVLFVAAWSDVGLCKKRPKPG    Manis sp
MVKSHIGGWILLLFVATWSDVGLCKKRPKPG    Canis lupus familiaris
MVKSHIGGWILLLFVATWSDVGLCKKRPKPG    Canis lupus familiaris
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG    Felis catus
MVKSHIGSWLLVLFVATWSDIGFCKKRPKPG    Mustela putorius
MVKSHIGSWLLVLFVATWSDIGFCKKRPKPG    Mustela putorius
MVKSHIGSWLLVLFVATWSDIGFCKKRPKPG    Mustela vison
MVKSHIGSWLLVLFVATWSDIGFCKKRPKPG    Mustela vison
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MGKIHLGYWFLALFIMTWSDLTLCKKPKPRPG    Monodelphis domestica
MGKIHLGYWFLALFIMTWSDLTLCKKPKPRPG    Monodelphis domestica
MGKIQLGYWILVLFIVTWSDLGLCKKPKPRPG    Trichosurus vulpecular
MGKIQLGYWILVLFIVTWSDLGLCKKPKPRPG    Trichosurus vulpecular
MGKIRLGYWILALFIVTWSDLGLCKKPKPRPG    Sarcophilus harrisii
MGRCLVVCWIAILLIVAWSDVSLCKKGKGRPS    Alligator mississipiensis
MARLLTTCCLLALLLAACTDVALSKKGKGKPS    Gallus gallus
MARLLTTCCLLALLLAACTDVALSKKGKGKPS    Gallus gallus
MAKLPGTSCLLLLLLLLGADLASCKKGKGKPG    Taeniopygia guttata
MAKLPGTSCLLLLLLLLGADLASCKKGKGKPG    Taeniopygia guttata
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=== The peculiar prion repeat expansion in Felids ===
=== The peculiar prion repeat expansion in Felids ===


After several false starts involving error-ridden or lab contaminated genBank submissions (eg DQ217930), accurate prion sequences have emerged for 10 species of carnivores. One sees immediately that foxes, dogs and coyotes are united by two short indels upstream of the repeat region that distinguish them from panda, mink, raccoon, lion and cat. The first region is quite homoplasic within laurasiatheres but the second is not: this indel resolve as a deletion in foxes, dogs and coyote.
After several false starts involving error-ridden or lab contaminated genBank submissions (eg DQ217930), accurate prion sequences have emerged for 10 species of carnivores. One sees immediately that foxes, dogs and coyotes are united by two short indels upstream of the repeat region that distinguish them from panda, mink, raccoon, lion and cat. The first region is quite homoplasic within laurasiatheres but the second is not: this indel resolves as a glycine insertion in a common ancestor of foxes, dogs and coyote and is restricted to Canidae.


Of greater interest is the very peculiar nonapeptide expansion in the two felids. This results in an unprecedented alanine insertion in position 3 of repeats 2-5. This cannot have resulted from coincidental separate point mutations but instead must have occured in repeat 2 and then been propagated by replication slippage to the other repeats, obliterating their ancestral octapeptide repeat sequences. This scenario implies felid repeats 3-5 will share synonymous bases of ancestral repeat 2 -- ie the sweep did not propagate from the fifth repeat in the 4-2 direction.  
Of greater interest is the very peculiar nonapeptide expansion in the two felids. This results in an unprecedented alanine insertion in position 3 of repeats 2-5. This cannot have resulted from coincidental separate point mutations but instead must have occured in repeat 2 and then been propagated by replication slippage to the other repeats, obliterating their ancestral octapeptide repeat sequences. This scenario implies felid repeats 3-5 will share synonymous bases of ancestral repeat 2 -- ie [http://www.mad-cow.org/00/topics.html#re as usual] the sweep did not propagate from the fifth repeat in the 4-2 direction.  


This means repeats 3-5 in felids are not homologous to say repeats 3-5 in human. Only repeats 1 and 2 have common descent. This mode of evolution is reminiscent of gene duplicates in which one copy corrects the other (gene conversion).
This means repeats 3-5 in felids are not homologous to say repeats 3-5 in human. Only repeats 1 and 2 have common descent. This mode of evolution is reminiscent of gene duplicates in which one copy corrects the other (gene conversion).


This unprecedented insertion of alanine and its propagation may provide a definitive character for all of Felidae if they occured in the stem of this clade. This must be the case [http://www.sciencemag.org/cgi/content/full/311/5757/73 according to a recent tree] showing lions basal which predicts all Felidae will have alanine nonarepeats.  
This unprecedented insertion of alanine and its propagation may provide a definitive character for all of Felidae if they occured in the stem of this clade. This must be the case [http://www.sciencemag.org/cgi/content/full/311/5757/73 according to a recent tree] showing lions basal -- all Felidae will then have alanine nonarepeats.  
[[Image:AlaNonarepeat.jpg|left]]
[[Image:AlaNonarepeat.jpg|left]]
The issue then concerns the [http://www.timetree.org/pdf/Eizirik2009Chap79.pdf immediate current outgroup] to felids, namely lingsangs (Prionodontidae). If the alanine nonarepeat (A9) character occurs there, then hyena, mongoose, suricat, fossa and palrm civit must be considered.  Additional species must be sequenced -- and possibly multiple individuals witin each species -- to resolve the timing in these little-studied species.
The issue then concerns the [http://www.timetree.org/pdf/Eizirik2009Chap79.pdf immediate current outgroup] to felids, namely linsangs (Prionodontidae). If the alanine nonarepeat (A9) character occurs there, then hyena, mongoose, suricat, fossa and palm civit must be considered.  Additional species must be sequenced -- and possibly multiple individuals witin each species -- to resolve the timing in these little-studied species.
 
One uninteresting outcome would be that all feliform species (a well-established wing of carnivores) have this character. Another uninteresting outcome would be occurence restricted to Felidae. However using the calculated tree dates, the probabliy of neither is 1-((52.9-49.0)+(37.8-10.8))/(52.8-10.8) = 27% assuming the A9 event falls equally at any time since divergence from the caniform group up to the divergence of lion and cat.  


One uninteresting outcome would be that all feliform species (a well-established wing of carnivores) have this character. Another uninteresting outcome would be occurence restricted to Felidae. However using the calculated tree dates, the probabliy of neither is 1-((52.9-49.0)+(37.8-10.8))/(52.8-10.8) = 25% assuming the A9 event is equally likely to fall at any time since divergence from the caniform group up to the divergence of lion and cat. This estimate is made unfavorable by the long stem time of 27 myr within Felidae that did not leave extant representatives. Thus there is a 64% chance that the A9 event occured in that time frame, ie that Felidae are unique in having this mutation.
This estimate is made unfavorable by the long stem time of 27 myr within Felidae that did not leave extant representatives. Thus there is a 64% chance that the A9 event occured in that time frame, ie that Felidae are unique in having this mutation. Little molecular data exists for Prionodon (29 fragmentary coding sequences, no mitochondrial genome) so statistical uncertainty in its node is high. Of these [[Opsin_evolution:_RBP3_%28IRBP%29|IRBP]] and [[Opsin_evolution:_transducins|GNAZ]] have been annotated here at genomeWiki.


It's not clear whether the insertion and propagation resulted within a single event or were temporally separated by millions of years. There may not exist sufficient extant species to resolve a two phase event if such occured. It would be very difficult for the A9 event to completely revert because this would require a deletion of the alanine in repeat 2 followed by its propagation to all the other repeats.
It's likely that the insertion of alanine and propagation to downstream repeats resulted from a single complex replication event (alanine codons differ only at middle position from glycine codons; glycine stutters are frequent) rather than temporal separation by millions of years. If so, no species will be found with an alanine restricted to repeat 2. There may not exist sufficient extant species to resolve a two phase event if such occured. It would be very difficult for the triple A9 event to revert by point mutations because this would require a deletion of the alanine in repeat 2 followed by its propagation to all the other repeats (or three separate deletion events of single alanines).


Note lion has 4 repeats whereas cat has 5 (the most abundant ancestral allele). Panda has 6 repeats, again not unusual within mammalian PRNP repeats.  
Note lion has 4 repeats whereas cat has 5 (the most abundant ancestral allele). Panda has 6 repeats, again not unusual within mammalian PRNP repeats.  
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Neither 4 nor 6 repeat number is associated with the amyloid disease state. A nonapeptide is the norm in marsupials in the downstream repeats and so too is unlikely to predispose to disease. Although the function of the PRNP gene product is not precisely known, it is likely that the alanine nonapeptide event lacks any phenotypic significance.
Neither 4 nor 6 repeat number is associated with the amyloid disease state. A nonapeptide is the norm in marsupials in the downstream repeats and so too is unlikely to predispose to disease. Although the function of the PRNP gene product is not precisely known, it is likely that the alanine nonapeptide event lacks any phenotypic significance.
Additional felid sequences that became available by July 2011 establish that the odd alanine event affects all extant felids (cougar is basal and exhibits the substitution). Thus this region provides no information on felid phylogeny. There is still no data available that would set an upper time bound relative to civits.
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  >PRNP_panLeo KPGGGWNTGG-SRYPGQGSPGGNRYP PQGGGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQ                  GGGTHSQWGK PSKPKTNMKHMAGAAAAGAVVGGLGGYMLG
  >Panthera le KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQ                  GGGTHSQWGK PSKPKTNMKHMAGAAAAGAVVGGLGGYMLG
  >Felis catus KPGGGWNTGG-SRYPGQGSPGGNRYP PQGGGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQ        GGGTHGQWGK PSKPKTNMKHMAGAAAAGAVVGGLGGYMLG
  >Neofelis    KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQ        GGGTHSQWGK PSKPKTNMKHMAGAAAAGAVVGGLGGYMLG
  >cat genom   KPGGGWNTGG-SRYPGQGSPGGNRYP PQGGGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQ        GGGTHGQWGK PSKPKTNMKHMAGAAAAGAVVGGLGGYMLG
>Puma        KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQ                  GGGTHSQWGK PSKPKTNMKHMAGAAAAGAVVGGLGGYMLG
  >Procyon lot KPGGGWNTGG-SRYPGQGNPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ         GGGSHGQWGK PNKPKTNMKHVAGAAAAGAVVGGLGGYMLG
  >Lynx cana   KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQ        GGGTHSQWGK PSKPKTNMKHMAGAAAAGAVVGGLGGYMLG
  >Mustela    KPGGGWNTGG-SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ        GGGSHGQWGK PSKPKTNIKHVAGAASAGAVVGG
  >Lynx rufus  KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQ        GGGTHSQWGK PSKPKTNMKHMAGAAAAGAVVGGLGGYMLG
  >Neovison    KPGGGWNTGG-SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ        GGGSHGQWGK PSKPKTNMKHVA
>Acinonyx    KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQ        GGGTHSQWGK PSKPKTNMKHMAGAAAAGAVVGGLGGYMLG
  >Ailuropoda  KPGGGWNTGG-SRYPGPGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGG.WGQPHGGGGWGQGGT.HGQWNK PSKPKTNMKHVAGAAAAGAVVGGLGGYMLG
>Felis catus KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQPH<font color="red">A</font>GGGWGQ         GGGTHGQWGK PSKPKTNMKHMAGAAAAGAVVGGLGGYMLG
  >Vulpes vulp KPGG-WNTGGGSRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ        GGGSHG.WGK PNKPKTNMKHVAGAAAAGAVVGGLGGYMLG
  >Mustela    KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ        GGGSHGQWGK PSKPKTNIKHVAGAASAGAVVGG
  >Vulpes lag  KPGG-WNTGGGSRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ        GGGSHG.WGK PNKPKTNMKHVAGAAAAGAVVGGLGGYMLG
  >Neovison    KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ        GGGSHGQWGK PSKPKTNMKHVA
  >Canis fam  KPGG-WNTGGGSRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ        GGGSHSQWGK
  >Ailuropoda  KPGGGWNTGG.SRYPGPGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGG.WGQPHGGGGWGQ.GGTHGQWNK PSKPKTNMKHVAGAAAAGAVVGGLGGYMLG
  >Canis la   KPGG-WNTGGGSRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ        GGGSHGQWGK PNKPKTNMKHVAGAAAAGAVVGGLGGYMLG
>Procyon lot KPGGGWNTGG.SRYPGQGNPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ        GGGSHGQWGK PNKPKTNMKHVAGAAAAGAVVGGLGGYMLG
>Phoca vitu  KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ        GGG.HGQWGK PNKPKTNMKHMAGAAAAGAVVGGLGGYMLG
>Odobenus    KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ        GGGSHGQWGK PNKPKTNMKHMAGAAAAGAVVGGLGGYMLG
  >Vulpes vulp KPGG<font color="blue">.</font>WNTGG<font color="blue">G</font>SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ        GGGSHG.WGK PNKPKTNMKHVAGAAAAGAVVGGLGGYMLG
  >Vulpes lag  KPGG<font color="blue">.</font>WNTGG<font color="blue">G</font>SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ        GGGSHG.WGK PNKPKTNMKHVAGAAAAGAVVGGLGGYMLG
>Canis la    KPGG<font color="blue">.</font>WNTGG<font color="blue">G</font>SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ        GGGSHGQWGK PNKPKTNMKHVAGAAAAGAVVGGLGGYMLG
  >Canis fam  KPGG<font color="blue">.</font>WNTGG<font color="blue">G</font>SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ        GGGSHSQWGK
  >Mephitis   KPGGGWNSGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ        GGGSHGQWGK PSKPKTNIKHMAGAAAAGAVVGGLGGYMLG
>Gulo gulo  KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGWGQPHGGGG.WGQ        GGGSHGQWGK PSKPKTNMKHVAGAAAAGAVVGGLGGYMLG
>Mustela    KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ        GGGSHGQWGK PSKPKTNMKHVAGAAAAGAVVGGLGGYMLG
>Ursus ame  KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ        GGGGHGQWGK PSKPKTNMKHVAGAAAAGAVVGGLGGYMLG
>Manis sp.  KPGGGWSTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGSWGQPH.GGGWGQPH.GGSWGQPHGGG.WGQPH      GGGTHSQWGK PSKPKTNMKHVAGAAAAGAVVGGLGGYMLG
>Cynopterus  KPGGGWNSGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGG.WGQ        GGGTHNQWNK PSKPKTNLKHVAGAAAAGAVVGGLGGYMLG
>Galeopterus KPGGWNTGG..SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ        GGGTHSQWGK PSKPKTNLKQMAGAAAAGAVVGGLGGYMLG
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>PRNP_panLeo Panthera leo (lion) EU236260 PMID:18256917
>PRNP_panLeo Panthera leo (lion) EU236260 PMID:18256917
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>Ailuropoda melanoleuca (panda) AY327449
>Ailuropoda melanoleuca (panda) AY327449
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPGGGWNTGGSRYPGPGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGTHGQWNK
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPGGGWNTGGSRYPGPGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGTHGQWNKPSKPKTNMKHVAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGSDYEDRY
PSKPKTNMKHVAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGSDYEDRY
 
>Puma concolor (cougar)
MVKGHIGGWILVLFVATWSDVGLCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQGGGTHSQWGKPSKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITVRQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQKESEAYYQRGASAILFSPPPVILLLSLLILLIGG
 
>Neofelis nebulosa (clouded leopard)
MVKGHIGGWILVLFVATWSDVGLCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQGGGTHSQWGKPSKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMNRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITVRQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQKESEAYYQRGASAILFSPPPVILLLSLLILLIGG
 
>Lynx canadensis (lynx) MVKGHIGGWILVLFVATWSDVGLCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQGGGTHSQWGKPSKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITVRQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQKESEAYYQRGASAILFSPPPVILLLSLLILLIGG
 
>Lynx rufus (lynx)
MVKGHIGGWILVLFVATWSDVGLCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQGGGTHSQWGKPSKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITVRQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQKEAEAYYQRGASAILFSPPPVILLLSLLILLIGG
 
>Acinonyx jubatus (cheetah)
MVKGHIGGWILVLFVATWSDVGLCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQGGGTHSQWGKPSKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITVRQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQKESEAYYQRGASAILFSPPPVILLLSLLILLIGG
 
>Ursus americanus (bear)
MVKSHIGGWILVLFVATWSDVGLCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGGHGQWGKPSKPKTNMKHVAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYKPVDQYSNQNSFVHDCVNITVKQHTVTTTTKGENFTETDIKIMERVVEQMCVTQYQREAEAYYQRGASAILFSPPPVILLISLLILLIVG
 
>Phoca vitulina (seal)
MVKSHIGGWILVLFVAAWSDVGLCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGGHGQWGKPNKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYKPVDQYSSQNNFVHDCVNITVKQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQKESEAYYQRGASAILFSPPPVILLISLLILLIVG
 
>Odobenus rosmarus (walrus)
MVKSHIGSWILVLFVATWSDVGLCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGSHGQWGKPNKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMNRYPNQVYYKPVDQYSNQNNFVHDCVNITVKQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQRESEAYYQRGASAILFSPPPVILLISLLILLIVG
 
>Mustela erminea (ermine)
MVKSHIGSWLLVLFVATWSDIGFCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGSHGQWGKPSKPKTNMKHVAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYKPVDQYSNQNNFVHDCVNITVKQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQRESEAYYQRGASAILFSPPPVILLISLLILLIVG
 
>Mephitis mephitis (striped skunk)
MVGSHIGGWILILFVATWSDVGLCKKRPKPGGGWNSGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGSHGQWGKPSKPKTNIKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRDNMYRYPNQVYYKPVDQYSNQNNFVHDCVNITVRQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQRESEAYYQRGASAMLFSPPPVILLISLLILLILG
 
>Gulo gulo (woverine) MVKSHIGSWLLVLFVATWSDIGFCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGSHGQWGKPSKPKTNMKHVAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMHRYPDQVYYKPVDQYSNQNNFVHDCVNITVKQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQRESEAYYQRGASAVLFSPPPVILLISLLILLIVG
 
>Manis sp. (pangolin)(pangolin)MMKSHVGGWILVLFVAAWSDVGLCKKRPKPGGGWSTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGSWGQPHGGGWGQPHGGSWGQPHGGGWGQPHGGGTHSQWGKPSKPKTNMKHVAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYNNQNNFVHDCVNITVKQHTVTTTTKGENFTETDIKMMERVVEQMCITQYQKEYQAASYQRGASVIFSSPPVILLIS
 
>Cynopterus sphinx (fruit bat)MVKSFVGGWILVLFVATWSDVGLCKKRPKPGGGWNSGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQGGGTHNQWNKPSKPKTNLKHVAGAAAAGAVVGGLGGYMLGSAMSRPMIHFGNDYEDRYYRENMNRYPNQVYYRPVDQYSNQNSFVHDCVNITVKQHTVTTTTKGENFTETDVKIMERVVEQMCITQYQQESRAAYHRGASVVVFSSPPVILLIS
 
>Galeopterus variegatus (flying lemur)
MENLGCWMLILFVATWSDIGLCKKRPKPGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGTHSQWGKPSKPKTNLKQMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITVKQHTVTTTTKGENFTETDIKIMERVVEQMCITQYQKEQQAYYQRGSSLALLSSPPVILLIS
   
   
Equus        KPGG-WNTGG-SRYPGQGSPGGNRYP  
Equus        KPGG-WNTGG-SRYPGQGSPGGNRYP  
Line 196: Line 268:
The Sarcophilus repeat region is of considerable interest -- the high GC content of this region makes it difficult to sequence and so provides a test of the 454 technology and Newbler assembler.  This region consists in placentals a five octapeptide repeat, in marsupials and platypus a five nona- or decapeptide residue repeat that may resolve fine details of the marsupial phylogenetic tree, which  in birds, lizards, turtles, frogs and fish is a hexapeptide repeat with trimeric internal substructure. Even though the single exon gene is clearly orthologous in all these species, the repeat regions within it are not directly comparable because they have expanded and contracted through replication slippage, plus experienced the odd repeat length change in marsupials and another in placentals.  
The Sarcophilus repeat region is of considerable interest -- the high GC content of this region makes it difficult to sequence and so provides a test of the 454 technology and Newbler assembler.  This region consists in placentals a five octapeptide repeat, in marsupials and platypus a five nona- or decapeptide residue repeat that may resolve fine details of the marsupial phylogenetic tree, which  in birds, lizards, turtles, frogs and fish is a hexapeptide repeat with trimeric internal substructure. Even though the single exon gene is clearly orthologous in all these species, the repeat regions within it are not directly comparable because they have expanded and contracted through replication slippage, plus experienced the odd repeat length change in marsupials and another in placentals.  


The Sarcophilus prion gene has very high coverage that overcomes the occasional problem with frameshifts and allows the gene to be accurately tiled. However familiarity with the gene and reliable fiducial sequences are key to rapid assembly of the full length gene. No sequencing difficulties were observed in the high GC repeat region. The gene is very normal and has no indications whatsoever of abnormal numbers of repeats (4) or prion disease disposition.
The Sarcophilus prion gene has very high coverage that overcomes the occasional problem with frameshifts and allows the gene to be accurately tiled. However familiarity with the gene and reliable fiducial sequences are key to rapid assembly of the full length gene. No sequencing difficulties were observed in the high GC repeat region. The gene has a normal number of repeats (4) not predisposing to prion disease.


[[Image:PRNPrepeat.jpg]]
[[Image:PRNPrepeat.jpg]]
[[Image:PrnpAmphib.jpg]]
<pre>
>PRNP_ambTig Ambystoma tigrinum (salamander) from 454 assembly
MGNRQMICWVLILVAVLWADTSLAKKGGKSKTGGGWGSNTNNRNTGGTWTNWNSGTNNNWNAGGNRGQNYNPQGGSNFNKQWKPPKSKPNMKM----VAGAAVAGALAGGVGGYVLG
NAMGRMRYNFDNQDDYSYYNQHSGRMPERVYRPRYVDDRPVTEERFVTDCYNMSAIEYIYKYDDGKNNSDVDPVEARVKSHVITQMCRSEYRMGNGVRKFFSDPFLVMSILLFLYFVVQ*
>PRNP_xenTro Xenopus tropicalis
MPRSLWTCLVLISLVCTLTVSSKKSGSGKSKTGGWNNGNTGNTGNTGNNRNPNYPGGYGWNTGNTGNTGGSWGQQPYNPSGGSNFNNKQWKPPKSKTNMKAVAVGAAAGAIGGYMLG
NAVGRMNHHFDNPMESRYYNDYYNQMPDRVYRPMYRSEEYVSEDRFVTDCYNMSVTEYIIKPSEGKNGSDVNQLDTVVKSKIIREMCITEYRRGSGFKVLSNPWLILTITLFVYFVIE*
>PRNP_anoCar Anolis carolinensis (lizard)
MGKHQMTCWLAIFLLLIQANVSLAKKKPKPSGGGWNTGGQRQPGYPQQPGYPRNPGYPQQPGYPQQPGYPQRNPGYPQQPGYGGGYGGGYGGGYGGGYGSNPYGGKPWKPKPPKTNLKHVAGAAVGGAAVGALGGYLLG
RSMSNMQFGFPNQYDERWWYQNRDRYSDQVYHPPYNPSVSREVFVRDCVNVTVTEYIQPTGNQTADEVEMRVVPLVVREMCTEQYRLLSGVALSLLANPSLVFTITLALCFLIH*
>PRNP_gekGek Gekko gekko (gecko)
MRRFLVTCWIAVFLILLQTDVSLSKKGKNKPGGGYPQQPSYPQNPGYPRNPGYPQNPGYPHNPGYPGGGYPRNPGYPQNPGNPGGGYPRNPGYPQNPGNPGGGYPRNPGYPGGGGWNQPNSKPWKPKPPKSNMKHIAGAALGGAAAGALGGYLLG
SAMSNMNFRFNNHDEERWWNENRNRYSDQVYHPKYEPSMSRDVFVRDCVNITVKEFTETSGNQTQDEMEKKVVTRVVHEMCTEQYRLVSSVAVLLANPSMLLIITFVICYL</pre>


<pre>
<pre>
Line 284: Line 375:
  MLRSLWTSLVLISLVCALTVSSKKSGSGKSKTG Xenopus topicalis
  MLRSLWTSLVLISLVCALTVSSKKSGSGKSKTG Xenopus topicalis
   
   
<pre>
=== Non-placental prion sequences ===
>PRNP_sacHar Sarcophilus harrisii (tasmanian_devil) single exon gene YVLG like Dasypus
MGKIRLGYWILALFIVTWSDLGLCKKPKPRPGGGWNSGGSNRYPGQPGSAGGNRYPGWGHPQGGGTNWGQPHPGGSSWGQPHAGGSNWGQPHGGSNWGQ
SGSSYNQKWKPDKPKTNMKHMAGAAAAGAVLGGVGGYVLGSAMSRPIMHFGNDYEDRYYRENQYRYPNQVMYRPIDQYSSQNNFVHDCVNITVKQHTTTTTT
KGENFTETDIKIMERVVEQMCITQYQNEYRAAQYSYNMAFFSAPPVTLLLLGFLIFLIVS*


>PRNP_mdo Monodelphis domestica opossum, from frameshifted genomic
MGKIHLGYWFLALFIMTWSDLTLCKKPKPRPGGGWNSGGNRYPGQSGGWGHPQGGGTNWGQPHAGGSNWGQPRPGGSNWGQPHPGGSNWGQPHPGGSNWG
QAGSSYNQKWKPDKPKTNMKHVAGAAAAGAVVGGLGGYMLGSAMSRPIMHFGNDYEDRYYRENQYRYPNQVMYRPIDQYNNQNNFVHDCVNITVKQHTTT
TTTKGENFTETDIKIMERVVEQMCITQYQNEYRSAYSVAFFSAPPVTLLLLSFLIFLIVS*


>PRNP_tvu Trichosurus vulpecular brushtail opossum
>PRNP_monDom Monodelphis domestica opossum, from frameshifted genomic
MGKIQLGYWILVLFIVTWSDLGLCKKPKPRPGGGWNSGGSNRYPGQPGSPGGNRYPGWGHPQGGGTNWGQPHPGGSNWGQPHPGGSSWGQPHGGSNWGQGGY
MGKIHLGYWFLALFIMTWSDLTLCKKPKPRPGGGWNSGGNRYPGQSGGWGHPQGGGTNWGQPHAGGSNWGQPRPGGSNWGQPHPGGSNWGQPHPGGSNWGQAGSSYNQKWKPDKPKTNMKHVAGAAAAGAVVGGLGGYMLG
NKWKPDKPKTNLKHVAGAAAAGAVVGGLGGYMLGSAMSRPVIHFGNEYEDRYYRENQYRYPNQVMYRPIDQYSSQNNFVHDCVNITVKQHTTTTTTKGENFTETDIKIMERVVEQM
SAMSRPIMHFGNDYEDRYYRENQYRYPNQVMYRPIDQYNNQNNFVHDCVNITVKQHTTTTTTKGENFTETDIKIMERVVEQMCITQYQNEYRSAYSVAFFSAPPVTLLLLSFLIFLIVS*
CITQYQAEYEAAAQRAYNMAFFSAPPVTLLFLSFLIFLIVS*
 
>PRNP_sacHar Sarcophilus harrisii (tasmanian_devil) single exon gene YVLG like Dasypus
>PRNP_meu Macropus eugenii (tammar wallaby)
MGKIRLGYWILALFIVTWSDLGLCKKPKPRPGGGWNSGGSNRYPGQPGSAGGNRYPGWGHPQGGGTNWGQPHPGGSSWGQPHAGGSNWGQPHGGSNWGQSGSSYNQKWKPDKPKTNMKHMAGAAAAGAVLGGVGGYVLG
MAKIQLGYWILALFIVTWSELGLCKKPKTRPGGGWNSGGSNRYPGQPGSPGGNRYPGWGHPQGGGTNWGQPHPGGSSWGQPHAGGSNWGQPHGGSNWGQ
SAMSRPIMHFGNDYEDRYYRENQYRYPNQVMYRPIDQYSSQNNFVHDCVNITVKQHTTTTTTKGENFTETDIKIMERVVEQMCITQYQNEYRAAQYSYNMAFFSAPPVTLLLLGFLIFLIVS*
GGGSYGKWKPDKPKTNLKHVAGAAAAGAVVGGLGGYMLGSAMSRPVMHFGNEYEDRYYRENQYRYPNQVMYRPIDQYGSQNSFVHDCVNITVKQHTTTTTT
KGENFTETDIKIMERVVEQMCITQYQNEYQAAQRYYNMAFFSAPPVTLLLLSFLIFLIVS*
>PRNP_macEug Macropus eugenii (tammar wallaby)
MAKIQLGYWILALFIVTWSELGLCKKPKTRPGGGWNSGGSNRYPGQPGSPGGNRYPGWGHPQGGGTNWGQPHPGGSSWGQPHAGGSNWGQPHGGSNWGQGGGSYGKWKPDKPKTNLKHVAGAAAAGAVVGGLGGYMLG
SAMSRPVMHFGNEYEDRYYRENQYRYPNQVMYRPIDQYGSQNSFVHDCVNITVKQHTTTTTTKGENFTETDIKIMERVVEQMCITQYQNEYQAAQRYYNMAFFSAPPVTLLLLSFLIFLIVS*
>PRNP_triVul Trichosurus vulpecular brushtail opossum
MGKIQLGYWILVLFIVTWSDLGLCKKPKPRPGGGWNSGGSNRYPGQPGSPGGNRYPGWGHPQGGGTNWGQPHPGGSNWGQPHPGGSSWGQPHGGSNWGQGGYNKWKPDKPKTNLKHVAGAAAAGAVVGGLGGYMLG
SAMSRPVIHFGNEYEDRYYRENQYRYPNQVMYRPIDQYSSQNNFVHDCVNITVKQHTTTTTTKGENFTETDIKIMERVVEQMCITQYQAEYEAAAQRAYNMAFFSAPPVTLLFLSFLIFLIVS*
 
>PRNP_ornAna  Ornithorhynchus anatinus platypus fragment
mGKSPVHHWIIDICVVHLERRCRGHLHPNPCPGGRCVQQQPNRYPGQPATPGGWGHPQGGGASWGHPQGGGSNWGHPQGGGASWGHPQGGGYSKYKPDKPKTGMKHVAGAAAAGAVVGGLGGYMIG
SAMSRPPMHFGNEFEDRYYRENQNRYSNQVYYRPVDQYGSQDGFVRDCVNITVTQHTVTTTEGKNLNETDVKIMTRVLEQMCVNLY
>PRNP_croPor Crocodylus porosus (crocodile)
MGRCLVICWIAILLIVAWSDVSLCKKGKGRPSGGGWNTGSQRNPQNPG.WGQHYNQKPHK.NKPGLGSVAGAAAAGAVVGGVGGYMLG
SALSGMHYRFSNPDESRWWNENSNRYPNSVYYKQYQEPVTQDRFVYDCVNVTVTSYKLEPSQNPNMTE...........METKVMHQVIEQRCTQQYQEYRLASSVKQLFSDPLL.ILGTVLVIFLAMH
>PRNP_allMis Alligator mississippiensis (alligator)
MGRCLVVCWIAILLIVAWSDVSLCKKGKGRPSGGGWNTGNQRNQNPG.WGQHYNQKPHK.NKPGLGSVAGAAAAGAVVGGVGGYMLG
SALSGMHYRFNNPDENRWWNENNNRYPNSVYYKQYPEPVNQDRFVYDCVNITVTNYKLEPSQNPNMTE...........METKVMHQVIEQRCTQQYREYRLASRVKQLFSDPSL.ILGTMLVIFLAMH
>PRNP_galGal Gallus gallus (chicken)
MARLLTTCCLLALLLAACTDVALSKKGKGKPSGGGWGAGSHRQGWGQGYNPSSGGSYHNQKPWKPHKTNFKHVAGAAAAGAVVGGLGGYAMG
RVMSGMNYHFDSPDEYRWWSENSARYPNRVYYRDYSSPVPQDVFVADCFNITVTEYSIGPAAKKNTSEAVAAANQTEVEMENKVVTKVIREMCVQQYREYRLASGIQLHPADTWLAVLLLLLTTLFAMH
>PRNP_melGal Meleagris gallopavo (turkey)
MARLLTTCCLLALLLAACTDVALS.KKGKGKPGGSWGAGSHRQQGYNPSSGGSYHNQKPWKPPKTNFKHVAGAAAAGAVVGGLGGYAMG
GRVMSGMNYRFDSPDEYRWWNENSARYPNRVYYRDYSGPVSQDVFVADCFNITVTEYSIGPAAKKNTSEAVPAANQTEVEMENKVVTKVIREMCVQQYREYRLASGIQLHPADTWLAVLLLLATLFAMH
>PRNP_taeGut Taeniopygia guttata (finch)
MAKLPGTSCLLLLLLLLLGADLASCKKGKGKPGGGGWGTGSRQPSSGGNYH.QKPWKAPKPKTNLKHVAGAAAAGAVVGGLGGYAMG
RVMSGMQYRFDSPDEYRWWSENAARYPNQVYYRDYRGGAVPQDVFVADCFNITVTEHNIGPAAKKNASEAGAALNQTEAELETRVVTKVIREMCIQQYQEYRLAAGTRPRLAADAALAALLLLALAALR
>PRNP_chrPic Chrysemys picta (painted_turtle) MRLSRHPPTIWLQYCVSQQFYTSGCSLNQIIIFYRLIT?
MGRYRITCWIVILLVVMWSDVSFSKKGKGKGGGGGNTGSNRNGQHYNPAGGGTNFKNQKPWKPDKPKTNMKAMAGAAVAGAVVGGLGGYALG
SAMSGMRMNFDRPEERQWWSENSNRYPNQVYYKEYNDRSVPEGRFVRDCVNITVTEYKIDPNENQNVTQVEARVMKQVIQEMCMQQYQQYQLASGVKLLSDPSLMLIIMLVIFFVMH*
>PRNP_traScr Trachemys scripta (red-eared slider)
MGRYRLTCWIVVLLVVMWSDVSFSKKGKGKGGGGGNTGSNRNPGYPGGGGQHYNPAGGGTNFKNQKPWKPDKPKTNMKAMAGAAAAGAVVGGLGGYALG
SAMSGMRMNFDRPEERQWWNENSNRYPNQVYYKEYNDRSVPEGRFVRDCLNNTVTEYKIDPNENQNVTQVEVRVMKQVIQEMCMQQYQQYQLASGVKLLSDPSLMLIIMLVIFFVMH
>PRNP_pelSin Pelodiscus sinensis (soft-shelled turtle)
MGRHLISCWIIVLFVAMWSDVSLAKKGKGKTGKGWKPAKPKTNLKAVAGAAAAGAVVGGIGGIALG
SAMSGMRMNFDRPDESRWWNENQNRYPNQVYYREYGDRSVPRGTFVNDCVNITVTEYKIDPKENQNVTEIEVKVLKRVIQEMCMQQYQKYQLASGVKLLLCDPLLMLMIMLVFFLVMR
>PRNP_anoCar Anolis carolinensis (lizard)
MGKHQMTCWLAIFLLLIQANVSLAKKKPKPSGGGWNTGGQRQGSNPYGGKPWKPKPPKTNLKHVAGAAVGGAAVGALGGYLLG
RSMSNMQFGFPNQYDERWWYQNRDRYSDQVYHPPYNPSVSREVFVRDCVNVTVTEYIQPTGNQTADEVEMRVVPLVVREMCTEQYRLLSGVALSLLANPSLVFTITLALCFLIH*
>PRNP1_pytMol Python molurus (python) closest to gekko
NPAHPPPYPANPPNPGYFPHQPNYPQNPNWGHYDPKPWKPKSPKTKLKHTAGAAIAGAAAGALGGYFLG
RAMSKLHFHFNNQNEERWWYENRHRYSDRVYYPQYIQPVPQDIFVRDCVNITVKEYIEPSGNETEDEIEARVVKHVVREMCIEQYRTFSSSS
>PRNP2_pytMol Python molurus (python) closest to gekko
                  GGYGGGYGGGYGGGQYSKPWKPKPPKPKMKHVAGAAVAGVAAGAVGGYLLG
RAMSNLNFGFNNPYESQWWYENRNRYSDQVYYPKYDQPVSRDVFVRDCTNVTVTEYIEPSGNKTADDMERKVVTQVVHQMCTEQYRLMSGVASLLANPSVLVMVTLILCFLIH*
>PRNP_bunMul Bungarus multicinctus (many-banded krait) terminal fragment
ANEkCMEMYPRLTVFTMSGSYYNNKPETATTLEIKSEFKHGEGAVLANSPGGVSGHNAPNNAVSDLHFSFENALFLIHPFAISIITLITPFLIF*
>PRNP_gekGek Gekko gekko (gecko)
MRRFLVTCWIAVFLILLQTDVSLSKKGKNKPGGGYGGGYPRNPGYPGGGGWNQPNSKPWKPKPPKSNMKHIAGAALGGAAAGALGGYLLG
SAMSNMNFRFNNHDEERWWNENRNRYSDQVYHPKYEPSMSRDVFVRDCVNITVKEFTETSGNQTQDEMEKKVVTRVVHEMCTEQYRLVSSVAVLLANPSMLLIITFVICYL
>PRNP_ambTig Ambystoma tigrinum (salamander) from 454 assembly
MGNRQMICWVLILVAVLWADTSLAKKGGKSKTGGGWGSNTNNRNTGGTWTNWNSGTNNNWNAGGNRGQNYNPQGGSNFNKQWKPPKSKPNMKM----VAGAAVAGALAGGVGGYVLG
NAMGRMRYNFDNQDDYSYYNQHSGRMPERVYRPRYVDDRPVTEERFVTDCYNMSAIEYIYKYDDGKNNSDVDPVEARVKSHVITQMCRSEYRMGNGVRKFFSDPFLVMSILLFLYFVVQ*
   
   
>PRNP_oan Ornithorhynchus anatinus platypus fragment
>PRNP_xenTro Xenopus tropicalis
PHWGKSPVHHWIIDICVVHLERRCRGHLHPNPCPGGRCVQQQPNRYPGQPATPGGWGHPQGGGASWGHPQGGGSNWGHPQGGGASWGHPQGGGYSKYKPDKPKTG
  MPRSLWTCLVLISLVCTLTVSSKKSGSGKSKTGGWNNGNTGNTGNTGNNRNGSWGQQPYNPSGGSNFNNKQWKPPKSKTNMKAVAVGAAAGAIGG<font color=red>YMLG</font>
MKHVAGAAAAGAVVGGLGGYMIGSAMSRPPMHFGNEFEDRYYRENQNRYSNQVYYRPVDQYGSQDGFVRDCVNITVTQHTVTTTEGKNLNETDVKIMTRVLEQMCVNLY
NAVGRMNHHFDNPMESRYYNDYYNQMPDRVYRPMYRSEEYVSEDRFVTDCYNMSVTEYIIKPSEGKNGSDVNQLDTVVKSKIIREMCITEYRRGSGFKVLSNPWLILTITLFVYFVIE*
</pre>


[[Image:PrnpGardot.png|left]]


>PRNP_latChu Latimeria chalumnae AFYH01209858 8969 bp may start at MRRYLFA, no synteny available in contig
MDFNIQRKESSATLPFLCNLQVYTMRRYLFAVWIAVLLIAVFSDVSFSKKGGSKKKPWSNK
PASKGYQPVPNSYQPVPNSYQPGKSSKKTAMKMAGAAAVGAIAGAGLG<font color=red>YALG</font>
GGHHFIPRIDFDSSEEERYRYHSNPSSRYNQNYNQPYDTQPEESTLFIELCYNNTITNLDASHGLSVSPTGKTQTQE
DLELKKQFIKYKCYMKYIEIRNSDSQYAGSAGESIHHFSGALFVHSFMMFLSFFLQ*
   
   
>PRNP_lepOcu Lepisosteus oculatus (spotted_gar) dna dotplot at left shows internal repeat
MLRPAVRLSLLALLLLLGLHCDPAWGKGRGGGSRGGGSKSSGSKGSSWNFGKSKTGQTGSTGQTRNTGTAAGK
PNPGSYPKQQYPAGGYPQQYPNQNPGGAGANPGGYPNQYPAGGYPNQNPGRAGANPGGYPNQYPAGGYPNQYPNQN
PGRAGANPGGYPNQYPAGGYPNQYPGGYPNQYPARGGVNPGGYPNQYPAAGGYPHAYPGGAGYPGGGQGWGQPAGYPNWNPNNKFP
SPRFGGYGHGAGGYGAGGSPFSRTAQDMGYGPSHKSKGFGKKAAMAAGVGAVAGMAVG<font color=blue>YGLG</font>
RFPRPNFNFHSPEEAHYYNHYMWRRYGSRSTDENDYGRDYQYNPPPQGYDSFMDNCIYSDSYLQKQTDTRGAPNPKGAKRP
DLLPQPEATPPPASDGPAPGHTPGNAPGNPGAEPNGTLPSQVNNSTANGTQAVSDAGLAMPSPQGTGPDGEGPGIPSPSLG
EQEQDDNDTVSIMEIGYPELIEQLKVRRCVEMYITGTQQLPLCQGLVLLVTTSLTLLTSTLLLQ* 0
<br clear=all>
[[Image:PRNPcoelo.gif|left]]
 


[[Category:Comparative Genomics]]
[[Category:Comparative Genomics]]

Latest revision as of 20:53, 24 September 2018

Introduction

The prion gene has many interesting evolutionary aspects. A few of those -- involving indels with phylogenetic interest - are explored below.

The signal peptide indel establishes Euarchontoglires

The prion gene PRNP exhibits a 6bp indel in its amino-terminal signal peptide that contributed historically to establishing the clade Euarchontoglires. From consideration of outgroups, the indel is a deletion (reducing signal pepide length from 31 to 29) rather than an insertion. It occurs in all species of rodents, rabbits, treeshrews, flying lemurs and primates sequenced to date but not in any other species of mammal.

Remarkably, this indel distribution has held up even as the number of genera sequenced has come to exceed 100. The billions of years of branch length represented by this data suggest that the deletion was a very rare event not subject to independent reoccurence (in effect homoplasy-free). Note it does not occur in a compositionally simple region (strings of leucines are common interiorly). As a typical mammalian gene as of November 08 can only be recovered from about 40 species, meaning similar rare genetic events cannot be as stringently evaluted as in PRNP.

Consequently this data set strongly conflicts with the never-ending computer proposals placing mouse basal relative to dog and human, ie (mouse,(dog,human)), which would require both a global revision of the well-established super-ordinal mammalian tree and in PRNP highly non-parsimonious multiple events both bizarrely located basally at the two unrelated divergence stems (very dense phylogenetic sampling has the effect of squeezing the window on homoplasy).

Signal region indels are not especially rare among orthologs to the 4500-odd human genes with signal peptides of which 595 are experimentally validated, despite steric requirements of the binding pocket of the signal processing complex SRP. In actuality the distribution of signal peptide length is fairly broad. These indels can be rapidly screened in batches of 25 by Blat alignment relative to the 44 available vertebrate genomes.

However few of these indels have any phylogenetic depth. It does not appear that the PRNP indel in euarchontoglires has any significant effect on cell targeting by the signal peptide (or subsequent membrane topology). It is not that indels in signal peptides are so rare but rather narrowly windowed basal events in large clades.

Below is data from 112 species: 

MA--NLGCWMLVLFVATWSDLGLCKKRPKPG     Homo sapiens
MA--NLGCWMLVLFVATWSDLGLCKKRPKPG     Pan troglodytes
MA--NLGCWMLVLFVATWSDLGLCKKRPKPG     Gorilla gorilla
MA--NLGCWMLVLFVATWSDLGLCKKRPKPG     Pongo pygmaeus
MA--NLGCWMLVLFVATWSDLGLCKKRPKPG     Nomascus leucogenys
MA--NLGCWMLVLFVATWSDLGLCKKRPKPG     Hylobates lar
MA--NLGCWMLVLFVATWSDLGLCKKRPKPG     Symphalangus syndactylus
MA--NLGCWMLVLFVATWSDLGLCKKRPKPG     Macaca arctoides
MA--NLGCWMLVLFVATWSDLGLCKKRPKPG     Macaca fascicularis
MA--NLGCWMLVLFVATWSDLGLCKKRPKPG     Macaca fuscata
MA--NLGCWMLVLFVATWSDLGLCKKRPKPG     Macaca mulatta
MA--NLGCWMLVLFVATWSDLGLCKKRPKPG     Macaca nemestrina
MA--NLGCWMLVLFVATWSDLGLCKKRPKPG     Papio hamadryas
MA--NLGCWMLFLFVATWSDLGLCKKRPKPG     Callithrix jacchus
MA--NLGCWMLVLFVATWSDLGLCKKRPKPG     Cebus apella
MA--NLGCWMLVVFVATWSDLGLCKKRPKPG     Cercopithecus aethiops
MA--NLGCWMLVVFVATWSDLGLCKKRPKPG     Cercopithecus dianae
MA--NLGCWMLVLFVATWSDLGLCKKRPKPG     Colobus guereza
MA--NLGCWMLVLFVATWSDLGLCKKRPKPG     Presbytis francoisi
MA--NLGCWMLVLFVATWSDLGLCKKRPKPG     Saimiri sciureus
ME--NLGCWMLILFVATWSDIGLCKKRPKPG     Galeopterus variegatus
MA--KLGYWLLVLFVATWSDVGLCKKRPKPG     Tarsius syrichta
MA--NLGCWMLVVFVATWSDVGLCKKRPKPG     Microcebus murinus
MA--RLGCWMLVLFVATWSDIGLCKKRPKPG     Otolemur garnettii
ME--NLGCWMLILFVATWSDIGLCKKRPKPG     Cynocephalus variegatus
MA--QLGCWLMVLFVATWSDVGLCKKRPKPG     Tupaia belangeri
MA--NLGYWLLALFVTMWTDVGLCKKRPKPG     Mus musculus
MA--NLGYWLLALFVTTCTDVGLCKKRPKPG     Rattus norvegicus
MA--NLGYWLLALFVTTCTDVGLCKKRPKPG     Rattus rattus
MA--NAGCWLLVLFVATWSDTGLCKKRPKPG     Cavia porcellus
MA--NLGYWLLALFVTTWTDVGLCKKRPKPG     Apodemus sylvaticus
MA--NLGCWLLVLFVATWSDLGLCKKRTKPG     Dipodomys ordii
MA--NLSYWLLAFFVTTWTDVGLCKKRPKPG     Clethrionomys glareolus
MA--NLSYWLLALFVATWTDVGLCKKRPKPG     Cricetulus griseus
MA--NLSYWLLALFVATWTDVGLCKKRPKPG     Cricetulus migratorius
MA--NLGYWLLALFVTMWTDVGLCKKRPKPG     Meriones unguiculatus
MA--NLSYWLLALFVAMWTDVGLCKKRPKPG     Mesocricetus auratus
MA--NLGYWLLALFVATWTDVGLCKKRPKPG     Sigmodon fulviventer
MA--NLGYWLLALFVATWTDVGLCKKRPKPG     Sigmodon hispiedis
MV--NPGCWLLVLFVATLSDVGLCKKRPKPG     Spermophilus tridecemlineatus
MV--NPGYWLLVLFVATLSDVGLCKKRPKPG     Sciurus vulgaris
MA--HLGYWMLLLFVATWSDVGLCKKRPKPG     Oryctolagus cuniculus
MA--HLSYWLLVLFVAAWSDVGLCKKRPKPG     Ochotona princeps
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Bos taurus
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Bison bison
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Rangifer tarandus
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Alces alces
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Capreolus capreolus
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Kobus megaceros
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Connochaetes taurinus
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Ammotragus lervia
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Hippotragus niger
MVKSHMGSWILVLFVVTWSDVGLCKKRPKPG     Camelus dromedarius
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Capris hircus
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Cervus elaphus
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Cervus elaphus nelsoni
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Dama dama
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Odocoileus hemionus
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Odocoileus virginianus
MVKSHIGSWILVLFVAMWSDVALCKKRPKPG     Oryx leucoryx
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Ovibos moschatus
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Ovis aries
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Ovis canadensis
MVKSHIGSWILVLFVAMWSDVALCKKRPKPG     Tragelaphus strepsiceros
MVKSHIGGWILVLFVAAWSDIGLCKKRPKPG     Sus scrofa
MVKSHMGSWILVLFVVTWSDMGLCKKRPKPG     Vicugna vicugna
MVKSHVGGWILVLFVATWSDVGLCKKRPKPG     Equus caballus
MVRSHVGGWILVLFVATWSDVGLCKKRPKPG     Diceros bicornis
MVKSLVGGWILLLFVATWSDVGLCKKRPKPG     Myotis lucifugus
MVKNYIGGWILVLFVATWSDVGLCKKRPKPG     Pteropus vampyrus
MVKSHIANWILVLFVATWSDMGFCKKRPKPG     Tursiops truncatus
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Felis catus
MVKGHIGGWILVLFVATWSDVGLCKKRPKPG     Panthera leo
MVKGHIGGWILVLFVATWSDVGLCKKRPKPG     Puma concolor
MVKGHIGGWILVLFVATWSDVGLCKKRPKPG     Neofelis nebulosa
MVKGHIGGWILVLFVATWSDVGLCKKRPKPG     Lynx canadensis
MVKGHIGGWILVLFVATWSDVGLCKKRPKPG     Lynx rufus
MVKGHIGGWILVLFVATWSDVGLCKKRPKPG     Acinonyx jubatus
MVKSHIGGWILLLFVATWSDVGLCKKRPKPG     Vulpes vulpes
MVKSHIGGWILLLFVATWSDVGLCKKRPKPG     Vulpes lagopus
MVKSHIGSWLLVLFVATWSDIGFCKKWPKPG     Neovison vison
MVKSHIGGWILVLFVATWSDVGLCKKRPKPG     Ursus americanus
MVKSHIGGWILVLFVAAWSDVGLCKKRPKPG     Phoca vitulina
MVKSHIGSWILVLFVATWSDVGLCKKRPKPG     Odobenus rosmarus
MVGSHIGGWILILFVATWSDVGLCKKRPKPG     Mephitis mephitis
MVKSHIGSWLLVLFVATWSDIGFCKKRPKPG     Gulo gulo 
MMKSHVGGWILVLFVAAWSDVGLCKKRPKPG     Manis sp
MVKSHIGGWILLLFVATWSDVGLCKKRPKPG     Canis lupus familiaris
MVKSHIGSWLLVLFVATWSDIGFCKKRPKPG     Mustela putorius
MVKSHIGSWLLVLFVATWSDIGFCKKRPKPG     Mustela vison
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPG     Ailuropoda melanoleuca
MVKNHVGCWLLVLFVATWSEVGLCKKRPKPG     Erinaceus europaeus
MVTGHLGCWLLVLFMATWSDVGLCKKRPKPG     Sorex araneus
MVKSHLGCWIMVLFVATWSEVGLCKKRPKPG     Cyclopes didactylus
MVRSRVGCWLLLLFVATWSELGLCKKRPKPG     Dasypus novemcinctus
MVKGTVSCWLLVLVVAACSDMGLCKKRPKPG     Echinops telfairi
MVKSSLGCWILVLFVATWSDMGLCKKRPKPG     Elephas maximus
MVKSSLGCWILVLFVATWSDMGLCKKRPKPG     Loxodonta africana
MVKSSLGCWMLVLFVATWSDVGLCKKRPKPG     Procavia capensis
MMKSGLGCWILVLFVATWSDVGLCKKRPKPG     Orycteropus afer
MVKSGLGCWILVLFVATWSDVGVCKKRPKPG     Trichechus manatus
MAKIQLGYWILALFIVTWSELGLCKKPKTRPG    Macropus eugenii
MGKIHLGYWFLALFIMTWSDLTLCKKPKPRPG    Monodelphis domestica
MGKIQLGYWILVLFIVTWSDLGLCKKPKPRPG    Trichosurus vulpecular
MGKIRLGYWILALFIVTWSDLGLCKKPKPRPG    Sarcophilus harrisii
MGRCLVVCWIAILLIVAWSDVSLCKKGKGRPS    Alligator mississipiensis
MARLLTTCCLLALLLAACTDVALSKKGKGKPS    Gallus gallus
MAKLPGTSCLLLLLLLLGADLASCKKGKGKPG    Taeniopygia guttata
MARLLTTCCLLALLLAACTDVALSKKGKGKPG    Meleagris gallopavo
MGKHQMTCWLAIFLLLIQANVSLAKK-KPKPS    Anolis carolinensis
MRRFLVTCWIAVFLILLQTDVSLSKKGKNKPG    Gekko gekkko
MGRYRLTCWIVVLLVVMWSDVSFSKKGKGKGG    Trachemys scripta
MGRHLISCWIIVLFVAMWSDVSLAKKGKGKTG    Pelodiscus sinensis
MPQSLWTCLVLISLICTLTVSSKKSGGGKSKTG   Xenopus laevis
MLRSLWTSLVLISLVCALTVSSKKSGSGKSKTG   Xenopus topicalis

The peculiar prion repeat expansion in Felids

After several false starts involving error-ridden or lab contaminated genBank submissions (eg DQ217930), accurate prion sequences have emerged for 10 species of carnivores. One sees immediately that foxes, dogs and coyotes are united by two short indels upstream of the repeat region that distinguish them from panda, mink, raccoon, lion and cat. The first region is quite homoplasic within laurasiatheres but the second is not: this indel resolves as a glycine insertion in a common ancestor of foxes, dogs and coyote and is restricted to Canidae.

Of greater interest is the very peculiar nonapeptide expansion in the two felids. This results in an unprecedented alanine insertion in position 3 of repeats 2-5. This cannot have resulted from coincidental separate point mutations but instead must have occured in repeat 2 and then been propagated by replication slippage to the other repeats, obliterating their ancestral octapeptide repeat sequences. This scenario implies felid repeats 3-5 will share synonymous bases of ancestral repeat 2 -- ie as usual the sweep did not propagate from the fifth repeat in the 4-2 direction.

This means repeats 3-5 in felids are not homologous to say repeats 3-5 in human. Only repeats 1 and 2 have common descent. This mode of evolution is reminiscent of gene duplicates in which one copy corrects the other (gene conversion).

This unprecedented insertion of alanine and its propagation may provide a definitive character for all of Felidae if they occured in the stem of this clade. This must be the case according to a recent tree showing lions basal -- all Felidae will then have alanine nonarepeats.

AlaNonarepeat.jpg

The issue then concerns the immediate current outgroup to felids, namely linsangs (Prionodontidae). If the alanine nonarepeat (A9) character occurs there, then hyena, mongoose, suricat, fossa and palm civit must be considered. Additional species must be sequenced -- and possibly multiple individuals witin each species -- to resolve the timing in these little-studied species.

One uninteresting outcome would be that all feliform species (a well-established wing of carnivores) have this character. Another uninteresting outcome would be occurence restricted to Felidae. However using the calculated tree dates, the probabliy of neither is 1-((52.9-49.0)+(37.8-10.8))/(52.8-10.8) = 27% assuming the A9 event falls equally at any time since divergence from the caniform group up to the divergence of lion and cat.

This estimate is made unfavorable by the long stem time of 27 myr within Felidae that did not leave extant representatives. Thus there is a 64% chance that the A9 event occured in that time frame, ie that Felidae are unique in having this mutation. Little molecular data exists for Prionodon (29 fragmentary coding sequences, no mitochondrial genome) so statistical uncertainty in its node is high. Of these IRBP and GNAZ have been annotated here at genomeWiki.

It's likely that the insertion of alanine and propagation to downstream repeats resulted from a single complex replication event (alanine codons differ only at middle position from glycine codons; glycine stutters are frequent) rather than temporal separation by millions of years. If so, no species will be found with an alanine restricted to repeat 2. There may not exist sufficient extant species to resolve a two phase event if such occured. It would be very difficult for the triple A9 event to revert by point mutations because this would require a deletion of the alanine in repeat 2 followed by its propagation to all the other repeats (or three separate deletion events of single alanines).

Note lion has 4 repeats whereas cat has 5 (the most abundant ancestral allele). Panda has 6 repeats, again not unusual within mammalian PRNP repeats. Here it cannot be assumed that sequencing one individual animal produces a representative allele for that population; indeed the reference human genome shows 4 repeats even though 98% of the population has 5 repeats.

Neither 4 nor 6 repeat number is associated with the amyloid disease state. A nonapeptide is the norm in marsupials in the downstream repeats and so too is unlikely to predispose to disease. Although the function of the PRNP gene product is not precisely known, it is likely that the alanine nonapeptide event lacks any phenotypic significance.

Additional felid sequences that became available by July 2011 establish that the odd alanine event affects all extant felids (cougar is basal and exhibits the substitution). Thus this region provides no information on felid phylogeny. There is still no data available that would set an upper time bound relative to civits. 

                                           1        2        3       4        5        6
>Panthera le KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQ                  GGGTHSQWGK PSKPKTNMKHMAGAAAAGAVVGGLGGYMLG
>Neofelis    KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQ         GGGTHSQWGK PSKPKTNMKHMAGAAAAGAVVGGLGGYMLG
>Puma        KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQ                  GGGTHSQWGK PSKPKTNMKHMAGAAAAGAVVGGLGGYMLG
>Lynx cana   KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQ         GGGTHSQWGK PSKPKTNMKHMAGAAAAGAVVGGLGGYMLG
>Lynx rufus  KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQ         GGGTHSQWGK PSKPKTNMKHMAGAAAAGAVVGGLGGYMLG
>Acinonyx    KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQ         GGGTHSQWGK PSKPKTNMKHMAGAAAAGAVVGGLGGYMLG
>Felis catus KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQ         GGGTHGQWGK PSKPKTNMKHMAGAAAAGAVVGGLGGYMLG
>Mustela     KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ         GGGSHGQWGK PSKPKTNIKHVAGAASAGAVVGG
>Neovison    KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ         GGGSHGQWGK PSKPKTNMKHVA
>Ailuropoda  KPGGGWNTGG.SRYPGPGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGG.WGQPHGGGGWGQ.GGTHGQWNK PSKPKTNMKHVAGAAAAGAVVGGLGGYMLG
>Procyon lot KPGGGWNTGG.SRYPGQGNPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ         GGGSHGQWGK PNKPKTNMKHVAGAAAAGAVVGGLGGYMLG
>Phoca vitu  KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ         GGG.HGQWGK PNKPKTNMKHMAGAAAAGAVVGGLGGYMLG
>Odobenus    KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ         GGGSHGQWGK PNKPKTNMKHMAGAAAAGAVVGGLGGYMLG
>Vulpes vulp KPGG.WNTGGGSRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ         GGGSHG.WGK PNKPKTNMKHVAGAAAAGAVVGGLGGYMLG
>Vulpes lag  KPGG.WNTGGGSRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ         GGGSHG.WGK PNKPKTNMKHVAGAAAAGAVVGGLGGYMLG
>Canis la    KPGG.WNTGGGSRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ         GGGSHGQWGK PNKPKTNMKHVAGAAAAGAVVGGLGGYMLG
>Canis fam   KPGG.WNTGGGSRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ         GGGSHSQWGK
>Mephitis    KPGGGWNSGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ         GGGSHGQWGK PSKPKTNIKHMAGAAAAGAVVGGLGGYMLG
>Gulo gulo   KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGWGQPHGGGG.WGQ         GGGSHGQWGK PSKPKTNMKHVAGAAAAGAVVGGLGGYMLG
>Mustela     KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ         GGGSHGQWGK PSKPKTNMKHVAGAAAAGAVVGGLGGYMLG
>Ursus ame   KPGGGWNTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ         GGGGHGQWGK PSKPKTNMKHVAGAAAAGAVVGGLGGYMLG
>Manis sp.   KPGGGWSTGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGSWGQPH.GGGWGQPH.GGSWGQPHGGG.WGQPH       GGGTHSQWGK PSKPKTNMKHVAGAAAAGAVVGGLGGYMLG
>Cynopterus  KPGGGWNSGG.SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGG.WGQ         GGGTHNQWNK PSKPKTNLKHVAGAAAAGAVVGGLGGYMLG
>Galeopterus KPGGWNTGG..SRYPGQGSPGGNRYP PQGGGGWGQPH.GGGWGQPH.GGGWGQPH.GGGWGQPHGGGGWGQ         GGGTHSQWGK PSKPKTNLKQMAGAAAAGAVVGGLGGYMLG

>PRNP_panLeo Panthera leo (lion) EU236260 PMID:18256917
MVKGHIGGWILVLFVATWSDVGLCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQGGGTHSQWGKPSKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMNRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITVRQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQKESEAYYQRGASAILFSPPPVILLLSLLILLIGG

>Felis catus (cat) EU588730
MVKGHIGGWILVLFVATWSDVGLCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQGGGTHGQWGKPSKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITVRQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQKESEAYYQRGASAILFSPPPVILLLSLLILLIGG

>Felis catus (cat) genome misassembly but trace ti|662129434 is good
MVKGHIGGWILVLFVATWSDVGLCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQGGGTHGQWGKPSKPKTNMKHMAGAAAAGAVVGGLGGYMLG

>Vulpes vulpes (fox) EF571898  MVKSHIGGWILLLFVATWSDVGLCKKRPKPGGWNTGGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGSHGWGKPNKPKTNMKHVAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPDQVYYRPVDQYSNQNNFVRDCVNITVKQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQKESEAYYQRGASAILFSPPPVILLISLLILLIVG

>Vulpes lagopus (Arctic fox) EU365392
MVKSHIGGWILLLFVATWSDVGLCKKRPKPGGWNTGGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGSHGWGKPNKPKTNMKHVAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPDQVYYRPVDQYSNQNNFVRDCVNITVKQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQKESEAYYQRGASAILFSPPPVILLISLLILLIVG

>Procyon lotor (raccoon) AY208166
FCKKRPKPGGGWNTGGSRYPGQGNPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGSHGQWGKPNKPKTNMKHVAGAAAAGA VVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYKPVDQYSNQNNFVHDCVNITVKQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQRESEAYYQRGASAILFS PPPV

>Mustela putorius furo (ferret) GD181110
MVKSHIGSWLLVLFVATWSDIGFCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGSHGQWGK
PSKPKTNIKHVAGAASAGAVVGGCLWF

>Neovison vison (ferret) EF508270
MVKSHIGSWLLVLFVATWSDIGFCKKWPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGSHGQWGKPSKPKTNMKHVA
 
>Canis familiaris (dog) genome
MVKSHIGGWILLLFVATWSDVGLCKKRPKPGGWNTGGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGSHSQWGK

>Canis latrans (coyote) FJ232956
VKSHIGGWILLLFVATWSDVGLCKKRPKPGGWNTGGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGSHGQWGKPNKPKTNMKHVAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPDQVYYRPVDQYSNQNNFVRDCVNITVKQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQKESEAYYQRGASAI

>Ailuropoda melanoleuca (panda) AY327449
MVKSHIGSWILVLFVAMWSDVGLCKKRPKPGGGWNTGGSRYPGPGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGTHGQWNKPSKPKTNMKHVAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGSDYEDRY

>Puma concolor (cougar)
MVKGHIGGWILVLFVATWSDVGLCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQGGGTHSQWGKPSKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITVRQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQKESEAYYQRGASAILFSPPPVILLLSLLILLIGG

>Neofelis nebulosa (clouded leopard)
MVKGHIGGWILVLFVATWSDVGLCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQGGGTHSQWGKPSKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMNRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITVRQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQKESEAYYQRGASAILFSPPPVILLLSLLILLIGG

>Lynx canadensis (lynx) MVKGHIGGWILVLFVATWSDVGLCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQGGGTHSQWGKPSKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITVRQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQKESEAYYQRGASAILFSPPPVILLLSLLILLIGG

>Lynx rufus (lynx)
MVKGHIGGWILVLFVATWSDVGLCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQGGGTHSQWGKPSKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITVRQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQKEAEAYYQRGASAILFSPPPVILLLSLLILLIGG

>Acinonyx jubatus (cheetah)
MVKGHIGGWILVLFVATWSDVGLCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQPHAGGGWGQGGGTHSQWGKPSKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITVRQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQKESEAYYQRGASAILFSPPPVILLLSLLILLIGG

>Ursus americanus (bear)
MVKSHIGGWILVLFVATWSDVGLCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGGHGQWGKPSKPKTNMKHVAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYKPVDQYSNQNSFVHDCVNITVKQHTVTTTTKGENFTETDIKIMERVVEQMCVTQYQREAEAYYQRGASAILFSPPPVILLISLLILLIVG

>Phoca vitulina (seal)
MVKSHIGGWILVLFVAAWSDVGLCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGGHGQWGKPNKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYKPVDQYSSQNNFVHDCVNITVKQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQKESEAYYQRGASAILFSPPPVILLISLLILLIVG

>Odobenus rosmarus (walrus)
MVKSHIGSWILVLFVATWSDVGLCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGSHGQWGKPNKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMNRYPNQVYYKPVDQYSNQNNFVHDCVNITVKQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQRESEAYYQRGASAILFSPPPVILLISLLILLIVG

>Mustela erminea (ermine)
MVKSHIGSWLLVLFVATWSDIGFCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGSHGQWGKPSKPKTNMKHVAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYKPVDQYSNQNNFVHDCVNITVKQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQRESEAYYQRGASAILFSPPPVILLISLLILLIVG

>Mephitis mephitis (striped skunk)
MVGSHIGGWILILFVATWSDVGLCKKRPKPGGGWNSGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGSHGQWGKPSKPKTNIKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRDNMYRYPNQVYYKPVDQYSNQNNFVHDCVNITVRQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQRESEAYYQRGASAMLFSPPPVILLISLLILLILG

>Gulo gulo (woverine) MVKSHIGSWLLVLFVATWSDIGFCKKRPKPGGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGSHGQWGKPSKPKTNMKHVAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMHRYPDQVYYKPVDQYSNQNNFVHDCVNITVKQHTVTTTTKGENFTETDMKIMERVVEQMCVTQYQRESEAYYQRGASAVLFSPPPVILLISLLILLIVG

>Manis sp. (pangolin)(pangolin)MMKSHVGGWILVLFVAAWSDVGLCKKRPKPGGGWSTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGSWGQPHGGGWGQPHGGSWGQPHGGGWGQPHGGGTHSQWGKPSKPKTNMKHVAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYNNQNNFVHDCVNITVKQHTVTTTTKGENFTETDIKMMERVVEQMCITQYQKEYQAASYQRGASVIFSSPPVILLIS

>Cynopterus sphinx (fruit bat)MVKSFVGGWILVLFVATWSDVGLCKKRPKPGGGWNSGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQGGGTHNQWNKPSKPKTNLKHVAGAAAAGAVVGGLGGYMLGSAMSRPMIHFGNDYEDRYYRENMNRYPNQVYYRPVDQYSNQNSFVHDCVNITVKQHTVTTTTKGENFTETDVKIMERVVEQMCITQYQQESRAAYHRGASVVVFSSPPVILLIS

>Galeopterus variegatus (flying lemur)
MENLGCWMLILFVATWSDIGLCKKRPKPGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGGWGQGGGTHSQWGKPSKPKTNLKQMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITVKQHTVTTTTKGENFTETDIKIMERVVEQMCITQYQKEQQAYYQRGSSLALLSSPPVILLIS
 
Equus        KPGG-WNTGG-SRYPGQGSPGGNRYP 
Erinaceus    KPGG-WNSGG-SRYPGQGSSGSNRY
Bos taurus   KPGGGWNTGG-SRYPGQGSPGGNRY
Lama pacos   KPGGGWNTGG-SRYPGQGSPGGK
Tursiops     KPGGGWNTGG-SRYPGQGSPGGNRYP 
Myotis       KPGGG-NTGG-SRYPGQGSPGGNR
Pteropus     KPGGGGSSGG-SRYPGQGSPGGNRY

PRNP marsupial and platypus repeat region in transition

The Sarcophilus repeat region is of considerable interest -- the high GC content of this region makes it difficult to sequence and so provides a test of the 454 technology and Newbler assembler. This region consists in placentals a five octapeptide repeat, in marsupials and platypus a five nona- or decapeptide residue repeat that may resolve fine details of the marsupial phylogenetic tree, which in birds, lizards, turtles, frogs and fish is a hexapeptide repeat with trimeric internal substructure. Even though the single exon gene is clearly orthologous in all these species, the repeat regions within it are not directly comparable because they have expanded and contracted through replication slippage, plus experienced the odd repeat length change in marsupials and another in placentals.

The Sarcophilus prion gene has very high coverage that overcomes the occasional problem with frameshifts and allows the gene to be accurately tiled. However familiarity with the gene and reliable fiducial sequences are key to rapid assembly of the full length gene. No sequencing difficulties were observed in the high GC repeat region. The gene has a normal number of repeats (4) not predisposing to prion disease.

PRNPrepeat.jpg

PrnpAmphib.jpg 

>PRNP_ambTig Ambystoma tigrinum (salamander) from 454 assembly
MGNRQMICWVLILVAVLWADTSLAKKGGKSKTGGGWGSNTNNRNTGGTWTNWNSGTNNNWNAGGNRGQNYNPQGGSNFNKQWKPPKSKPNMKM----VAGAAVAGALAGGVGGYVLG
NAMGRMRYNFDNQDDYSYYNQHSGRMPERVYRPRYVDDRPVTEERFVTDCYNMSAIEYIYKYDDGKNNSDVDPVEARVKSHVITQMCRSEYRMGNGVRKFFSDPFLVMSILLFLYFVVQ*

>PRNP_xenTro Xenopus tropicalis
MPRSLWTCLVLISLVCTLTVSSKKSGSGKSKTGGWNNGNTGNTGNTGNNRNPNYPGGYGWNTGNTGNTGGSWGQQPYNPSGGSNFNNKQWKPPKSKTNMKAVAVGAAAGAIGGYMLG
NAVGRMNHHFDNPMESRYYNDYYNQMPDRVYRPMYRSEEYVSEDRFVTDCYNMSVTEYIIKPSEGKNGSDVNQLDTVVKSKIIREMCITEYRRGSGFKVLSNPWLILTITLFVYFVIE*

>PRNP_anoCar Anolis carolinensis (lizard)
MGKHQMTCWLAIFLLLIQANVSLAKKKPKPSGGGWNTGGQRQPGYPQQPGYPRNPGYPQQPGYPQQPGYPQRNPGYPQQPGYGGGYGGGYGGGYGGGYGSNPYGGKPWKPKPPKTNLKHVAGAAVGGAAVGALGGYLLG
RSMSNMQFGFPNQYDERWWYQNRDRYSDQVYHPPYNPSVSREVFVRDCVNVTVTEYIQPTGNQTADEVEMRVVPLVVREMCTEQYRLLSGVALSLLANPSLVFTITLALCFLIH*

>PRNP_gekGek Gekko gekko (gecko)
MRRFLVTCWIAVFLILLQTDVSLSKKGKNKPGGGYPQQPSYPQNPGYPRNPGYPQNPGYPHNPGYPGGGYPRNPGYPQNPGNPGGGYPRNPGYPQNPGNPGGGYPRNPGYPGGGGWNQPNSKPWKPKPPKSNMKHIAGAALGGAAAGALGGYLLG
SAMSNMNFRFNNHDEERWWNENRNRYSDQVYHPKYEPSMSRDVFVRDCVNITVKEFTETSGNQTQDEMEKKVVTRVVHEMCTEQYRLVSSVAVLLANPSMLLIITFVICYL
Dasypus         MVRSRVGCWLLLLFVATWSELGLC KK.RPKPGGGWNTGG  SRYPGQ GSPGG NRYP     PQGGG  WGQ PHGGG  WGQ PHGGG  WGQ PHGGG  WGQ PHGGG  WGQ  GGAHGQ                
Trichosurus     MGKIQLGYWILVLFIVTWSDLGLC KKPKPRPGGGWNSGGS NRYPGQPGSPGG NRYPGWGH PQGGGTNWGQ PHPGGSNWGQ PHPGGSSWGQ PH GGSNWGQ             GG YN  
Sarcophilus     MGKIRLGYWILALFIVTWSDLGLC KKPKPRPGGGWNSGGS NRYPGQPGSAGG NRYPGWGH PQGGGTNWGQ PHPGGSSWGQ PHAGGSNWGQ PH.GGSNWGQ            SGSSYNQ
Monodelphis     MGKIHLGYWFLALFIMTWSDLTLC KKPKPRPGGGWNSGG  NRYPGQ    SG     GWGH PQGGGTNWGQ PHAGGSNWGQ PRPGGSNWGQ PHPGGSNWGQ PHPGGSNWGQ AGSSYNQ 
Macropus        MAKIQLGYWILALFIVTWSELGLC KKPKTRPGGGWNSGGS NRYPGQPGSPGG NRYPGWGH PQGGGTNWGQ PHPGGSSWGQ PHAGGSNWGQ PH.GGSNWGQ            GGGSYG
Ornithorhynchus ------------------------ -------GGGWNSG   NRYPGQPANPG      GWGH PQGGGASWGH PQGGGASWGH PQGGGSNWGH PQGGGASWGH PQ          GGGYS  

Dasypus         WNKPSKPKTNM KHVAGAAAAGAVVG LGGYLVGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRSVEQYSSEKNFVHD CV                         MERVVEQMCITQYQ 
Trichosurus     KWKPDKPKTNL KHVAGAAAAGAVVGGLGGYMLGSAMSRPVIHFGNEYEDRYYRENQYRYPNQVMYRPIDQYSSQNNFVHD CVNITVKQHTTTTTTKGENFTETDIKIMERVVEQMCITQYQN
Sarcophilus     KWKPDKPKTNM KHMAGAAAAGAVLGSLGGYVLGSAMSRPIMHFGNDYEDRYYRENQYRYPNQVMYRPIDQYSSQNNFVHD CVNITVKQHTTTTTTKGENFTETDIKIMERVVEQMCITQYQN
Monodelphis     KWKPDKPKTNM KHVAGAAAAGAVVGGLGGYMLGSAMSRPIMHFGNDYEDRYYRENQYRYPNQVMYRPIDQYNNQNNFVHD CVNITVKQHTTTTTTKGENFTETDIKIMERVVEQMCITQYQN
Macropus        KWKPDKPKTNL KHVAGAAAAGAVVGGLGGYMLGSAMSRPVMHFGNEYEDRYYRENQYRYPNQVMYRPIDQYGSQNSFVHD CVNITVKQHTTTTTTKGENFTETDIKIMERVVEQMCITQYQN
Ornithorhynchus KYKPDKPKTGM KHVAGAAAAGAVVGGLGGYMIGSAMSRPPMHFGNEFEDRYYRENQNRYPNQVYYRPVDHFCSQDGFVRD CVNITVTQHTVTTT.EGKNLNETDVKIMTRVLEQMC

The signal region of Sarcophilus PRNP is expected to show the same length as the other 3 known marsupial sequences, which is confirmed by the sequence. Placentals exhibit a one residue deletion relative to this ancestral length. 

MA--NLGCWMLVLFVATWSDLGLCKK--RPKPG Homo sapiens
MA--NLGCWMLVLFVATWSDLGLCKK--RPKPG Pan troglodytes
MA--NLGCWMLVLFVATWSDLGLCKK--RPKPG Gorilla gorilla
MA--NLGCWMLVLFVATWSDLGLCKK--RPKPG Pongo pygmaeus
MA--NLGCWMLVLFVATWSDLGLCKK--RPKPG Nomascus leucogenys
MA--NLGCWMLVLFVATWSDLGLCKK--RPKPG Hylobates lar
MA--NLGCWMLVLFVATWSDLGLCKK--RPKPG Symphalangus syndactylus
MA--NLGCWMLVLFVATWSDLGLCKK--RPKPG Macaca arctoides
MA--NLGCWMLVLFVATWSDLGLCKK--RPKPG Macaca fascicularis
MA--NLGCWMLVLFVATWSDLGLCKK--RPKPG Macaca fuscata
MA--NLGCWMLVLFVATWSDLGLCKK--RPKPG Macaca mulatta
MA--NLGCWMLVLFVATWSDLGLCKK--RPKPG Macaca nemestrina
MA--NLGCWMLVLFVATWSDLGLCKK--RPKPG Papio hamadryas
MA--NLGCWMLFLFVATWSDLGLCKK--RPKPG Callithrix jacchus
MA--NLGCWMLVLFVATWSDLGLCKK--RPKPG Cebus apella
MA--NLGCWMLVVFVATWSDLGLCKK--RPKPG Cercopithecus aethiops
MA--NLGCWMLVVFVATWSDLGLCKK--RPKPG Cercopithecus dianae
MA--NLGCWMLVLFVATWSDLGLCKK--RPKPG Colobus guereza
MA--NLGCWMLVLFVATWSDLGLCKK--RPKPG Presbytis francoisi
MA--NLGCWMLVLFVATWSDLGLCKK--RPKPG Saimiri sciureus
MA--KLGYWLLVLFVATWSDVGLCKK--RPKPG Tarsius syrichta
MA--NLGCWMLVVFVATWSDVGLCKK--RPKPG Microcebus murinus
MA--RLGCWMLVLFVATWSDIGLCKK--RPKPG Otolemur garnettii
ME--NLGCWMLILFVATWSDIGLCKK--RPKPG Cynocephalus variegatus
MA--QLGCWLMVLFVATWSDVGLCKK--RPKPG Tupaia belangeri
MA--NLGYWLLALFVTMWTDVGLCKK--RPKPG Mus musculus
MA--NLGYWLLALFVTTCTDVGLCKK--RPKPG Rattus norvegicus
MA--NAGCWLLVLFVATWSDTGLCKK--RPKPG Cavia porcellus
MA--NLGCWLLVLFVATWSDLGLCKK--RTKPG Dipodomys ordii
MV--NPGCWLLVLFVATLSDVGLCKK--RPKPG Spermophilus tridecemlineatus
MA--HLGYWMLLLFVATWSDVGLCKK--RPKPG Oryctolagus cuniculus
MA--HLSYWLLVLFVAAWSDVGLCKK--RPKPG Ochotona princeps
MVKSHIGSWILVLFVAMWSDVGLCKK--RPKPG Bos taurus
MVKSHIGGWILVLFVAAWSDIGLCKK--RPKPG Sus scrofa
MVKSHMGSWILVLFVVTWSDMGLCKK--RPKPG Vicugna vicugna
MVKSHVGGWILVLFVATWSDVGLCKK--RPKPG Equus caballus
MVRSHVGGWILVLFVATWSDVGLCKK--RPKPG Diceros bicornis
MVKSLVGGWILLLFVATWSDVGLCKK--RPKPG Myotis lucifugus
MVKNYIGGWILVLFVATWSDVGLCKK--RPKPG Pteropus vampyrus
MVKSHIANWILVLFVATWSDMGFCKK--RPKPG Tursiops truncatus
MVKSHIGGWILLLFVATWSDVGLCKK--RPKPG Canis lupus familiaris
MVKSHIGSWILVLFVAMWSDVGLCKK--RPKPG Felis catus
MVKSHIGSWLLVLFVATWSDIGFCKK--RPKPG Mustela putorius
MVKSHIGSWLLVLFVATWSDIGFCKK--RPKPG Mustela vison
MVKSHIGSWILVLFVAMWSDVGLCKK--RPKPG Ailuropoda melanoleuca
MVKNHVGCWLLVLFVATWSEVGLCKK--RPKPG Erinaceus europaeus
MVTGHLGCWLLVLFMATWSDVGLCKK--RPKPG Sorex araneus
MVKSHLGCWIMVLFVATWSEVGLCKK--RPKPG Cyclopes didactylus
MVRSRVGCWLLLLFVATWSELGLCKK--RPKPG Dasypus novemcinctus
MVKGTVSCWLLVLVVAACSDMGLCKK--RPKPG Echinops telfairi
MVKSSLGCWILVLFVATWSDMGLCKK--RPKPG Loxodonta africana
MVKSSLGCWMLVLFVATWSDVGLCKK--RPKPG Procavia capensis
MAKIQLGYWILALFIVTWSELGLCKKP-KTRPG Macropus eugenii
MGKIHLGYWFLALFIMTWSDLTLCKKP-KPRPG Monodelphis domestica
MGKIRLGYWILALFIVTWSDLGLCKKP-KPRPG Sacophilus harrisii
MGKIQLGYWILVLFIVTWSDLGLCKKP-KPRPG Trichosurus vulpecular
MARLLTTCCLLALLLAACTDVALSKKG-KGKPS Gallus gallus
MAKLPGTSCLLLLLLLLGADLASCKKG-KGKPG Taeniopygia guttata
MARLLTTCCLLALLLAACTDVALSKKG-KGKPG Meleagris gallopavo
MGKHQMTCWLAIFLLLIQANVSLAKK--KPKPS Anolis carolinensis
MRRFLVTCWIAVFLILLQTDVSLSKKG-KNKPG Gekko gekkko
MGRYRLTCWIVVLLVVMWSDVSFSKKG-KGKGG Trachemys scripta (turtle)
MGRHLISCWIIVLFVAMWSDVSLAKKG-KGKTG Pelodiscus sinensis (turtle)
MPQSLWTCLVLISLICTLTVSSKKSGGGKSKTG Xenopus laevis
MLRSLWTSLVLISLVCALTVSSKKSGSGKSKTG Xenopus topicalis

Non-placental prion sequences

>PRNP_monDom Monodelphis domestica opossum, from frameshifted genomic
MGKIHLGYWFLALFIMTWSDLTLCKKPKPRPGGGWNSGGNRYPGQSGGWGHPQGGGTNWGQPHAGGSNWGQPRPGGSNWGQPHPGGSNWGQPHPGGSNWGQAGSSYNQKWKPDKPKTNMKHVAGAAAAGAVVGGLGGYMLG
SAMSRPIMHFGNDYEDRYYRENQYRYPNQVMYRPIDQYNNQNNFVHDCVNITVKQHTTTTTTKGENFTETDIKIMERVVEQMCITQYQNEYRSAYSVAFFSAPPVTLLLLSFLIFLIVS*

>PRNP_sacHar Sarcophilus harrisii (tasmanian_devil) single exon gene YVLG like Dasypus
MGKIRLGYWILALFIVTWSDLGLCKKPKPRPGGGWNSGGSNRYPGQPGSAGGNRYPGWGHPQGGGTNWGQPHPGGSSWGQPHAGGSNWGQPHGGSNWGQSGSSYNQKWKPDKPKTNMKHMAGAAAAGAVLGGVGGYVLG
SAMSRPIMHFGNDYEDRYYRENQYRYPNQVMYRPIDQYSSQNNFVHDCVNITVKQHTTTTTTKGENFTETDIKIMERVVEQMCITQYQNEYRAAQYSYNMAFFSAPPVTLLLLGFLIFLIVS*

>PRNP_macEug Macropus eugenii (tammar wallaby)
MAKIQLGYWILALFIVTWSELGLCKKPKTRPGGGWNSGGSNRYPGQPGSPGGNRYPGWGHPQGGGTNWGQPHPGGSSWGQPHAGGSNWGQPHGGSNWGQGGGSYGKWKPDKPKTNLKHVAGAAAAGAVVGGLGGYMLG
SAMSRPVMHFGNEYEDRYYRENQYRYPNQVMYRPIDQYGSQNSFVHDCVNITVKQHTTTTTTKGENFTETDIKIMERVVEQMCITQYQNEYQAAQRYYNMAFFSAPPVTLLLLSFLIFLIVS*

>PRNP_triVul Trichosurus vulpecular brushtail opossum
MGKIQLGYWILVLFIVTWSDLGLCKKPKPRPGGGWNSGGSNRYPGQPGSPGGNRYPGWGHPQGGGTNWGQPHPGGSNWGQPHPGGSSWGQPHGGSNWGQGGYNKWKPDKPKTNLKHVAGAAAAGAVVGGLGGYMLG
SAMSRPVIHFGNEYEDRYYRENQYRYPNQVMYRPIDQYSSQNNFVHDCVNITVKQHTTTTTTKGENFTETDIKIMERVVEQMCITQYQAEYEAAAQRAYNMAFFSAPPVTLLFLSFLIFLIVS*
 
>PRNP_ornAna  Ornithorhynchus anatinus platypus fragment
mGKSPVHHWIIDICVVHLERRCRGHLHPNPCPGGRCVQQQPNRYPGQPATPGGWGHPQGGGASWGHPQGGGSNWGHPQGGGASWGHPQGGGYSKYKPDKPKTGMKHVAGAAAAGAVVGGLGGYMIG
SAMSRPPMHFGNEFEDRYYRENQNRYSNQVYYRPVDQYGSQDGFVRDCVNITVTQHTVTTTEGKNLNETDVKIMTRVLEQMCVNLY

>PRNP_croPor Crocodylus porosus (crocodile)
MGRCLVICWIAILLIVAWSDVSLCKKGKGRPSGGGWNTGSQRNPQNPG.WGQHYNQKPHK.NKPGLGSVAGAAAAGAVVGGVGGYMLG
SALSGMHYRFSNPDESRWWNENSNRYPNSVYYKQYQEPVTQDRFVYDCVNVTVTSYKLEPSQNPNMTE...........METKVMHQVIEQRCTQQYQEYRLASSVKQLFSDPLL.ILGTVLVIFLAMH

>PRNP_allMis Alligator mississippiensis (alligator)
MGRCLVVCWIAILLIVAWSDVSLCKKGKGRPSGGGWNTGNQRNQNPG.WGQHYNQKPHK.NKPGLGSVAGAAAAGAVVGGVGGYMLG
SALSGMHYRFNNPDENRWWNENNNRYPNSVYYKQYPEPVNQDRFVYDCVNITVTNYKLEPSQNPNMTE...........METKVMHQVIEQRCTQQYREYRLASRVKQLFSDPSL.ILGTMLVIFLAMH

>PRNP_galGal Gallus gallus (chicken)
MARLLTTCCLLALLLAACTDVALSKKGKGKPSGGGWGAGSHRQGWGQGYNPSSGGSYHNQKPWKPHKTNFKHVAGAAAAGAVVGGLGGYAMG
RVMSGMNYHFDSPDEYRWWSENSARYPNRVYYRDYSSPVPQDVFVADCFNITVTEYSIGPAAKKNTSEAVAAANQTEVEMENKVVTKVIREMCVQQYREYRLASGIQLHPADTWLAVLLLLLTTLFAMH

>PRNP_melGal Meleagris gallopavo (turkey)
MARLLTTCCLLALLLAACTDVALS.KKGKGKPGGSWGAGSHRQQGYNPSSGGSYHNQKPWKPPKTNFKHVAGAAAAGAVVGGLGGYAMG
GRVMSGMNYRFDSPDEYRWWNENSARYPNRVYYRDYSGPVSQDVFVADCFNITVTEYSIGPAAKKNTSEAVPAANQTEVEMENKVVTKVIREMCVQQYREYRLASGIQLHPADTWLAVLLLLATLFAMH

>PRNP_taeGut Taeniopygia guttata (finch)
MAKLPGTSCLLLLLLLLLGADLASCKKGKGKPGGGGWGTGSRQPSSGGNYH.QKPWKAPKPKTNLKHVAGAAAAGAVVGGLGGYAMG
RVMSGMQYRFDSPDEYRWWSENAARYPNQVYYRDYRGGAVPQDVFVADCFNITVTEHNIGPAAKKNASEAGAALNQTEAELETRVVTKVIREMCIQQYQEYRLAAGTRPRLAADAALAALLLLALAALR

>PRNP_chrPic Chrysemys picta (painted_turtle) MRLSRHPPTIWLQYCVSQQFYTSGCSLNQIIIFYRLIT?
MGRYRITCWIVILLVVMWSDVSFSKKGKGKGGGGGNTGSNRNGQHYNPAGGGTNFKNQKPWKPDKPKTNMKAMAGAAVAGAVVGGLGGYALG
SAMSGMRMNFDRPEERQWWSENSNRYPNQVYYKEYNDRSVPEGRFVRDCVNITVTEYKIDPNENQNVTQVEARVMKQVIQEMCMQQYQQYQLASGVKLLSDPSLMLIIMLVIFFVMH*

>PRNP_traScr Trachemys scripta (red-eared slider)
MGRYRLTCWIVVLLVVMWSDVSFSKKGKGKGGGGGNTGSNRNPGYPGGGGQHYNPAGGGTNFKNQKPWKPDKPKTNMKAMAGAAAAGAVVGGLGGYALG
SAMSGMRMNFDRPEERQWWNENSNRYPNQVYYKEYNDRSVPEGRFVRDCLNNTVTEYKIDPNENQNVTQVEVRVMKQVIQEMCMQQYQQYQLASGVKLLSDPSLMLIIMLVIFFVMH

>PRNP_pelSin Pelodiscus sinensis (soft-shelled turtle)
MGRHLISCWIIVLFVAMWSDVSLAKKGKGKTGKGWKPAKPKTNLKAVAGAAAAGAVVGGIGGIALG
SAMSGMRMNFDRPDESRWWNENQNRYPNQVYYREYGDRSVPRGTFVNDCVNITVTEYKIDPKENQNVTEIEVKVLKRVIQEMCMQQYQKYQLASGVKLLLCDPLLMLMIMLVFFLVMR

>PRNP_anoCar Anolis carolinensis (lizard)
MGKHQMTCWLAIFLLLIQANVSLAKKKPKPSGGGWNTGGQRQGSNPYGGKPWKPKPPKTNLKHVAGAAVGGAAVGALGGYLLG
RSMSNMQFGFPNQYDERWWYQNRDRYSDQVYHPPYNPSVSREVFVRDCVNVTVTEYIQPTGNQTADEVEMRVVPLVVREMCTEQYRLLSGVALSLLANPSLVFTITLALCFLIH*

>PRNP1_pytMol Python molurus (python) closest to gekko
NPAHPPPYPANPPNPGYFPHQPNYPQNPNWGHYDPKPWKPKSPKTKLKHTAGAAIAGAAAGALGGYFLG
RAMSKLHFHFNNQNEERWWYENRHRYSDRVYYPQYIQPVPQDIFVRDCVNITVKEYIEPSGNETEDEIEARVVKHVVREMCIEQYRTFSSSS

>PRNP2_pytMol Python molurus (python) closest to gekko
                  GGYGGGYGGGYGGGQYSKPWKPKPPKPKMKHVAGAAVAGVAAGAVGGYLLG
RAMSNLNFGFNNPYESQWWYENRNRYSDQVYYPKYDQPVSRDVFVRDCTNVTVTEYIEPSGNKTADDMERKVVTQVVHQMCTEQYRLMSGVASLLANPSVLVMVTLILCFLIH*

>PRNP_bunMul Bungarus multicinctus (many-banded krait) terminal fragment
ANEkCMEMYPRLTVFTMSGSYYNNKPETATTLEIKSEFKHGEGAVLANSPGGVSGHNAPNNAVSDLHFSFENALFLIHPFAISIITLITPFLIF*

>PRNP_gekGek Gekko gekko (gecko)
MRRFLVTCWIAVFLILLQTDVSLSKKGKNKPGGGYGGGYPRNPGYPGGGGWNQPNSKPWKPKPPKSNMKHIAGAALGGAAAGALGGYLLG
SAMSNMNFRFNNHDEERWWNENRNRYSDQVYHPKYEPSMSRDVFVRDCVNITVKEFTETSGNQTQDEMEKKVVTRVVHEMCTEQYRLVSSVAVLLANPSMLLIITFVICYL

>PRNP_ambTig Ambystoma tigrinum (salamander) from 454 assembly
MGNRQMICWVLILVAVLWADTSLAKKGGKSKTGGGWGSNTNNRNTGGTWTNWNSGTNNNWNAGGNRGQNYNPQGGSNFNKQWKPPKSKPNMKM----VAGAAVAGALAGGVGGYVLG
NAMGRMRYNFDNQDDYSYYNQHSGRMPERVYRPRYVDDRPVTEERFVTDCYNMSAIEYIYKYDDGKNNSDVDPVEARVKSHVITQMCRSEYRMGNGVRKFFSDPFLVMSILLFLYFVVQ*

>PRNP_xenTro Xenopus tropicalis
MPRSLWTCLVLISLVCTLTVSSKKSGSGKSKTGGWNNGNTGNTGNTGNNRNGSWGQQPYNPSGGSNFNNKQWKPPKSKTNMKAVAVGAAAGAIGGYMLG
NAVGRMNHHFDNPMESRYYNDYYNQMPDRVYRPMYRSEEYVSEDRFVTDCYNMSVTEYIIKPSEGKNGSDVNQLDTVVKSKIIREMCITEYRRGSGFKVLSNPWLILTITLFVYFVIE*
PrnpGardot.png
>PRNP_latChu Latimeria chalumnae AFYH01209858 8969 bp may start at MRRYLFA, no synteny available in contig
MDFNIQRKESSATLPFLCNLQVYTMRRYLFAVWIAVLLIAVFSDVSFSKKGGSKKKPWSNK
PASKGYQPVPNSYQPVPNSYQPGKSSKKTAMKMAGAAAVGAIAGAGLGYALG
GGHHFIPRIDFDSSEEERYRYHSNPSSRYNQNYNQPYDTQPEESTLFIELCYNNTITNLDASHGLSVSPTGKTQTQE
DLELKKQFIKYKCYMKYIEIRNSDSQYAGSAGESIHHFSGALFVHSFMMFLSFFLQ*

>PRNP_lepOcu Lepisosteus oculatus (spotted_gar) dna dotplot at left shows internal repeat
MLRPAVRLSLLALLLLLGLHCDPAWGKGRGGGSRGGGSKSSGSKGSSWNFGKSKTGQTGSTGQTRNTGTAAGK
PNPGSYPKQQYPAGGYPQQYPNQNPGGAGANPGGYPNQYPAGGYPNQNPGRAGANPGGYPNQYPAGGYPNQYPNQN
PGRAGANPGGYPNQYPAGGYPNQYPGGYPNQYPARGGVNPGGYPNQYPAAGGYPHAYPGGAGYPGGGQGWGQPAGYPNWNPNNKFP
SPRFGGYGHGAGGYGAGGSPFSRTAQDMGYGPSHKSKGFGKKAAMAAGVGAVAGMAVGYGLG
RFPRPNFNFHSPEEAHYYNHYMWRRYGSRSTDENDYGRDYQYNPPPQGYDSFMDNCIYSDSYLQKQTDTRGAPNPKGAKRP
DLLPQPEATPPPASDGPAPGHTPGNAPGNPGAEPNGTLPSQVNNSTANGTQAVSDAGLAMPSPQGTGPDGEGPGIPSPSLG
EQEQDDNDTVSIMEIGYPELIEQLKVRRCVEMYITGTQQLPLCQGLVLLVTTSLTLLTSTLLLQ* 0


PRNPcoelo.gif
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