Coding indels: PRNP
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.
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.
>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*
>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
