Dating Doppel (PRND): Difference between revisions

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<h3>Dating doppel: missing from bird and fish genomes -- but present in marsupial, lizard and frog</h3>
<h3>Dating doppel: missing from bird and fish genomes -- but present in marsupial, lizard and frog</h3>


The prion and doppel genes represent a local tandem duplication that has descended intact in most lineages with the two genes remaining adjacent and unpseudogenized (though both have spawned additional retroposed pseudogenes). When did this gene duplication take place, did it correlate with or facilitate an evolutionary advancement, and how have the (largely unknown) normal functions of the two genes since diverged? Retention of the second copy is somewhat puzzling in view of viability of PRNP knockouts, indeed [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15161660">double knockouts].
The prion and doppel genes represent a local tandem duplication that has descended intact in most lineages with the two genes remaining adjacent and unpseudogenized (though both spawned retroposed pseudogenes in later lineages). When did this gene duplication take place, did it correlate with or facilitate an evolutionary advantage, and how have the (largely unknown) normal functions of the original gene since diverged? Retention of either copy is already somewhat puzzling in view of viability of PRNP knockouts, indeed PRNP/PRND [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15161660 double knockouts].


The weak homology between prion and doppel, below 30% identity even for the conserved core, suggests either a quite ancient duplication (lamprey era?) followed by average divergence, or alternatively, a fairly recent duplication (tetrapod era?) followed by rapid evolution on the doppel side as it acquired a auxillary function (neofunctionalized). These possibilities can be distinguished by looking at earlier diverging species that put a date on the duplication event.
The strikingly weak homology between prion and doppel -- below 30% identity within-species even trimming to conserved core -- suggests either an ancient duplication (lamprey era?) followed by symmetric divergence at more or less average rates, or alternatively a recent duplication (tetrapod era?) followed by rapid [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18025270 asymmetrically fast] evolution on the doppel side as it neofunctionalized or subfunctionalized to a secondary function of the unduplicated gene. These possibilities can be distinguished by looking at earlier diverging species that bracket date on the duplication event.


If the duplication is old, then doppel should be found in various draft vertebrate genomes now available -- 34 mammals (see [[Genome completion status]]), chicken, lizard, frog, zebrafish, tetraodon, fugu, medaka, and stickleback. If gene order and orientation (synteny) are conserved, doppel will lie between PRNP and RASSF2, allowing highly diverged forms to be recognized that might give unconvincing blast matches. Of course synteny can be supplemented by conservation of internal signatures such as signal peptide, post-translationally modified arginine, disulfides, glycosylation sites, alpha helices, short beta sheet (YMLG in human), and GPI attachment. Repeat structure is trickier to use because it has been lost in all doppels and shifts from biphasic hexapeptide in frog, turtles, birds, and lizards to decapeptide (platypus), nonapeptide (marsupial), to octapeptide (placentals).
If the duplication is old, then doppel should be found in various draft vertebrate genomes now available -- 34 mammals (see [[Genome completion status]]) plus chicken, lizard, frog, zebrafish, tetraodon, fugu, medaka, and stickleback. If synteny (gene order and orientation) are conserved, doppel will lie between PRNP and RASSF2, allowing highly diverged forms to be recognized by blast focused to that intergene region that otherwise might be lost among whole-genome match debris). Synteny and weak blast support are hopefully supplemented by conservation of internal signatures such as signal peptide, post-translationally modified arginine, disulfides, glycosylation sites, alpha helices, short beta sheet (YMLG in human), and GPI attachment.  


The brushtail opossum (Trichosurus vulpecular) prion gene sequence was determined in 1995. It conserves structural elements overall but presents various anomalies such as nonapeptide repeats. Its sequence can be used as query at the [http://genome.cse.ucsc.edu/cgi-bin/hgGateway?hgsid=99826923&clade=vertebrate&org=Opossum&db=0 UCSC genome browser] to find a complete second marsupial PRNP sequence from Monodelphis domestica. The two proteins have  86% sequence identity (not including repeat region), not necessarily indicating faster divergence since marsupials have had longer to diverge than placental mammals. The two 'opossums' here are not closely related, Didelphimorphia vs Diprotodontia. The second marsupial genome (Macropus eugenii) has been released unassembled to NCBI trace archives; full length PRNP and PRND sequences are readily covered there by trace blastn.
Repeat structure is trickier to use because it has been totally lost in all PRND (at the time of duplication?) and in PRNP varies from wildly expanded in fish, biphasic hexapeptide in frog, turtles, birds, and lizards to decapeptide (platypus), nonapeptide (marsupial), or octapeptide (placentals) as discussed elsewhere [[Prion repeat evolution]]. Further, the number of observed repeats varies markedly across individuals (sometimes pathologically), an effect seen from birds to mammals. It is an unstable coding region of very high GC subject to frequent replication slippage with new variants constantly arising. There is no wild type allele, only a choice within population variants. This requires reconstructed ancestral nodes to consist of a reconstructed population. Consequently the region is not strictly speaking homologous across species and is only inappropriately included in orthologous alignments. The normal function if any is unknown; it cannot be assumed that a single function holds across species (knockins have no complementation assay). Thus the distribution of functions across PRNP and PRND must address possibly non-uniform function in PRNP across species.  


Monodelphis domestica PRND is located next to PRNP in the same orientation in a gapless region of the assembly. Within placental mammals, doppel homology is about 85% identity but this drops off to 46% relative to marsupial, indicating a relative fast-evolving protein in this lineage (but not yet a pseudogene). Indeed, with nearly PRNP gene sequences available in nearly a hundred species of placentals and the mammalian phylogenetic tree topology [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17322288,17975064 finally determined], clade-specific rate variations could be pursued in unusual detail, with a possible correlation with rates of doppel evolution.
PRND may never have been able to fully complement PRNP. Not only has the repeat region been lost (most parsimoniously at, or shortly after, duplication), but the two genes are asymmetrically positioned with respect to upstream promoters and regulatory elements of the original single gene, ie PRND is in the rain shadow of PRNP. After considerations involving dating and removing subsequently accrued retroposons, upstream non-coding elements were too far removed from the PRNP start codon in the ancestral genome to have been included in the original duplication. PRND must then have been transcribed by read-through (as seen today in rare mouse transcripts) which would have given it appropriate developmental and tissue expression from the get-go, perhaps at a reduced level that mitigated gene dosage while allowing more rapid divergence. In this asymmetric scenario, PRND only later developed transcription control regions in the intergenic region that could separately modulate expression.


Monotreme represents a still earlier divergence: PRNP  and PRND can be recovered from the newly released assembly of the platypus genome, Ornithorhynchus anatinus. This species, which diverged after birds but before the Metatherian/Eutherian split, has a decapeptide x 4 repeat (rather than a bird- or turtle-like hexapeptide. However its sequence, PQGGGASWGH, is unusual for its glutamine in second position and terminal histidine (reverse of usual mammal residues). In other respects it is conventional.  
Tandem gene duplications are thus quite different from large segmental (or whole genome) duplications. They require further stratification depending on whether parallel or inverted, whether inclusive or not of upstream regulatory regions, and whether or not in comparable euchromatin environments. Subsequent history is also important: PRNP and PRND have remained largely unperturbed but other tandem gene duplications have been followed by much later (thus lineage-specific) secondary events such as further tandem expansion, separating block inversions, translocation of one copy elsewhere, and deletion. Such events accrue roughly in proportion to elapsed time.  


The chicken genome is gap-free in this area and retains mammalian gene order and orientation (PRNP+, RASSF2-, and SCL23A-). However, no dopple gene occurs in chicken in the expected position. If prion gene duplication occurred prior to chicken divergence, then doppel decayed to an unrecognizable pseudogene, translocated to an unsequenced region, or has been deleted. No evidence for a decayed pseudogene is observed using a high-sensitivity blast of reconstructed ancestral doppel. The other bird genome underway, Taeniopygia guttata (finch), also lacks PRND.
Consequently older tandem gene duplications tend to have unique histories, undercutting any program to develop sweeping theories. Rate histories must speak to a single timeline (of reconstructed ancestral nodes leading to a fixed species) rather than to repeatedly bifurcated timelines of phylogenetic tree data that reference increasingly incomparable clades. The history of the PRNP/PRND tandem duplication below will illustrates that.


Very recently, a lizard genome became available, Anolis carolinensis. Using specialized methods, a full length PRND gene has be located in expected syntenic position and validated by retained internal signatures despite its very weak blast score. Similarly in the diploid frog, Xenopus tropicalis, an unmistakable frog doppel gene occurs at expected position and orientation. These results have a simple  parsimonious explanation: the PRND duplication predated amphibian divergence, followed by a lineage-specific deletion in the bird clade. Crocodile sequencing could refine the date of this event.
PRNP sequences are available at GenBank from over 100 species of placental mammal. Dozens more can be extracted from genome projects in various stages of completion. The lesser effort expended on PRND and its much rarer transcripts conspire with rapidly weakening percent identity to make advanced bioninformatic techniques necessary as pipeline annotation collapses.


In support, lizard and frog doppel queries retrieve solely mammalian and turtle PRND genes when back-blasted against the GenBank non-redundant nucleotide division. This argues against the idea of multiple independent duplications of the prion gene in lizard and frog distinct from a later lineage-specific duplication in mammals (with birds then never having a PRND to delete).  
The brushtail opossum (Trichosurus vulpecular) prion gene sequence was determined in 1995. It conserves structural elements overall but presents various anomalies such as nonapeptide repeats. Its sequence can be used as query at the [http://genome.cse.ucsc.edu/cgi-bin/hgGateway?hgsid=99826923&clade=vertebrate&org=Opossum&db=0 UCSC genome browser] to locate a second complete marsupial PRNP sequence from Monodelphis domestica. Monodelphis domestica PRND is located next to PRNP in the same orientation in a gapless region of the assembly, left- and right-flanked by syntenically appropriate genes. A third marsupial sequence (Macropus eugenii) is available from unassembled NCBI trace archives; full length PRNP and PRND sequences are readily covered there by trace blastn using opossum query, though synteny cannot be pursued. Marsupials have had longer to diverge than placental mammals; the two 'opossums' here are not closely related, Didelphimorphia vs Diprotodontia. Paired rate studies thus await PRND from Trichosurus vulpecular and a fossil calibration of an overall molecular clock for marsupial divergence.  


Note the more familiar tetraploid laboratory frog, Xenopus laevis, has two actively transcribed PRNP genes that differ slightly in the repeat-like region as well at a few individual amino acids. Their sequences are given below. No sign of doppel can be found in Xenopus laevis cDNA (unsurprisingly since doppel transcription is rare); no genome project is underway. There may be two doppels in this species, depending on the relative timing of PRNP duplication and the tetraploidization event and selective pressure to maintain two copies.
Monotreme represents an important earlier divergence. PRNP and PRND can be recovered from the newly released assembly of the platypus genome, Ornithorhynchus anatinus. This species, which diverged after birds but before the Theran split, has a PRNP decapeptide x 4 repeat (rather than a bird- or turtle-like hexapeptide. However its sequence, PQGGGASWGH, is unusual for its glutamine in second position and terminal histidine (reverse of usual mammal residues). In other respects it is conventional. Unfortunately neither sequence is available for echidna; these could be easily acquired because both genes consist of a single short coding exon.  


The prion gene in teleost fish has radically diverged from its mammalian counterpart especially in the repeat region but remains recognizable via various conserved anchor features, residual synteny, and weak homology. Fugu has a second PRNP gene on a different chromosome (resulting from the whole genome duplication in Teleostei) plus an apparent novel tandem duplication that resembles PRNP rather than PRND. Coelocanth genome has been proposed but not begun -- that could further refine the timing of PRND duplication. As it stands, that event occurred after teleost fish divergence but before that of amphibians, about 400 million years ago. The prion gene clearly represents the ancestral form and presumably function, ie, a doppel-like ancestor did not duplicate to a second gene that become PRNP. No counterpart of PRNP can be located in the initial release of the chondrichthyian genome, Callorhynchus milii, but that will be finished to higher coverage in a few months.
Within placental mammals, doppel homology runs at about 85% identity but this drops off to 48% relative to marsupial and 41% in platypus, indicating (relative to global proteomes) a fast-evolving protein not yet a pseudogene in any lineage (though it spawned 'processed' pseudogenes in kangaroo rat and stem xenarthra). Indeed, with the density of PRNP gene sequences in placentals and the mammalian phylogenetic tree topology [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17322288,17975064 finally determined], clade-specific rate variations could be pursued in unusual detail, along with any correlated doppel evolution. The ancestral boreoeuthere PRND and PRNP sequences provided below could facilitate that quest by providing non-roundtrip rates over a fixed 85 myr time interval. The ancestral sequences have a meagre 21% identity.


Doppels are evolving noticeably faster than prions but have not become pseudogenes in any species investigated to date. (Note very recent pseudogenes that have not yet acquired internal stop codons or loss of deeply invariant residues are difficult to detect.) It must be remembered that PRNP's globular region lies within the most slowly evolving quartile of mammalian genes. As a representative example, human/dog proteins have 78% identity for PRND but 87% for PRNP. A reconstructed ancestral mammal sequence for PRND shows no sign whatsoever of converging to a PRNP-like sequence, percent identity ancester-to-ancestor remains in the mid-20's. Since this uses up 100 million years of the 400 available, doppel evolved more drastically at an earlier time, perhaps soon after the duplication event.  
The chicken genome is gap-free in this area and retains mammalian gene order and orientation (RASSF2- PRNP+ SCL23A-). However, no dopple gene (nor evidence for a decayed pseudogene) occurs in chicken in the expected position despite various high-sensitivity blast probes (reconstructed ancestral doppel, anole PRND).  If prion gene duplication occurred prior to chicken divergence, then doppel has decayed to an unrecognizable pseudogene, translocated to region of gappy coverage, or deleted. The other bird genome underway, Taeniopygia guttata (finch), also lacks PRND. The intergenic region where PRND should lie, between PRNP and RASSF2, consists in chicken of a meagre 529 bp vs 122,057 bp in human, establishing a large indel has occured.  


To further investigate the co-evolution of PRNP and PRND, it is imperative to first collect gene sequences from a phylogenetically representative sample of species. PRNP tends to be over-sampled within Artiodactylia, indeed Bovidae. Doppel remains very poorly represented at dbEST even within much-studied mammals and enriched libraries, even in testis, a tissue where it is transcribed. The most economical explanation of the data is that doppel has a narrow function with limited and specialized expression in uncommon cell types, yet one important enough for gene retention.
Very recently, a lizard genome became available, Anolis carolinensis. Lizards are a sister group to birds. Using specialized methods, a full length PRND gene can be located in expected syntenic position and validated by retained internal signatures despite an exceedingly very weak blast match.  


However a respectable number of tetrapod doppel sequences have accumulated. In addition to genome projects, van Rheede and coworkers sequenced nine doppels from important early diverging clades of placental mammals. PRND from the chimpanzee genome has special interest for evaluating known human doppel polymorphisms to determine "wildtype" human. Macaque doppel can also the 2 amino acid deletion seen in human at position 122-123, showing this event predated old world monkey divergence. In fact that event can be precisely timed to the stem lying between tarsier and new world monkey divergence and shown non-homplasic using various genome projects underway:
Similarly the diploid frog, Xenopus tropicalis, has an unmistakable doppel gene at expected syntenic position and orientation. Some sequence uncertainty exists because of assembly issues and frameshifts in the two supporting ESTs. No doppel can be found in the (non-genomic) tetraploid frog, Xenopus laevis, though it has two actively transcribed PRNP genes that differ slightly in the repeat-like region as well at a few individual amino acids. There may be two in-paralog doppels in this species, depending on the relative timing of PRNP duplication and the tetraploidization event..


<pre>
These results have a simple parsimonious explanation: the PRND duplication predated amphibian divergence, it was retained in all lineages except birds, where a lineage-specific deletion occured bird clade. Crocodile sequencing of this region could further refine the date of this event.
PRND_hsa  ANQGEFQ--KPDNKLHQQVLWRLVQELCS  Homo  sapiens  (human)
PRND_ptr  ANQGEFQ--KPDNKLHQQVLWRLVRELCS  Pan  troglodytes  (chimp)
PRND_ggo  ANQGEFH--KPDNKLHQQVLWRLVRELCS  Gorilla  gorilla  (gorilla)
PRND_ppy  ANQGEFQ--KPDNKLHQQVLWRLVQELCS  Pongo  pygmaeus  (orang_sumatran)
PRND_nle  ANQGEFQ--KPDNKLHQRVLWRLVRELCS  Nomascus  leucogenys  (gibbon)
PRND_mml  ENQGEFQ--KPDNKLHQRVLWRLVQELCS  Macaca  mulatta  (rhesus)
PRND_pha  ANQGEFQ--KPDNKLHQRVLWRLVQELCS  Papio  hamadryas  (baboon)
PRND_cja  ANQAEFQ--KPDNKLHQRVLWRLVQELCS  Callithrix  jacchus  (marmoset_nwm)
PRND_tsy  ANAAERPREARDDPLHQRVLGRLVRELCS  Tarsius  syrichta  (tarsier)
PRND_mmr  ANQAEFAREKQD-KLHERILWRLTRELCS  Microcebus  murinus  (mouse_lemur)
PRND_tbe  ANQAEFSKEKQDNKLYQRVLWRLIKELCS  Tupaia  belangeri  (tree_shrew)
PRND_ocu  ANQGEFSREKQDNKLHQRVLWRLIKELCS  Oryctolagus  cuniculus  (rabbit)
PRND_opr  ANQGEFSREKQ-NKLHQRVLWRLIKELCS  Ochotona  princeps  (pika)
PRND_dor  ANQAEFAREMQD-KFYQRVLWRLTKELCA  Dipodomys  ordii  (kangaroo_rat)
PRND_str  ANQAEFSREKQDNKLHQRVLWRLIKELCS  Spermophilus  tridecemlineatus  (ground_squirrel)
PRND_rno  ANQAEFSREKQDSKLHQRVLWRLIKEICS  Rattus  norvegicus  (rat)
PRND_mmu  ANQAEFSREKQDSKLHQRVLWRLIKEICS  Mus  musculus  (mouse)
PRND_cpo  ANQAEFSREKQDNKLHQRILWRLIKELCS  Cavia  porcellus    (guinea_pig)
PRND_sar  ANQEELSREKHD-KLYQRVLWRLVRELCS  Sorex  araneus  (shrew)
PRND_eeu  ANQEELSREKHD-KLYQRVLWRLVRELCS  Erinaceus  europaeus  (hedgehog)
PRND_cfa  ANQEELSREKQDNKLHQRVLWRLIRELCS  Canis  familiaris  (dog)
PRND_fca  ANQEELSREKQDDKLYQRVLWRLNR-ECS  Felis  catus  (cat)
PRND_tte  ENQEELSREKQDDKLHQRILWRLIRELCS  Tapirus  terrestris  (tapir)
PRND_eca  ANQEELSQEKQDDKLYQRILWRLISELCS  Equus  caballus  (horse)
PRND_mlu  ANQEELSQERPDNRLHRRILWRLVRELCS  Myotis  lucifugus  (microbat)
PRND_csp  VNQEELSQEKQDKLLHQRILWQLIRELCS  Cynopterus  sphinx  (bat)
PRND_oar  ANQEELSREKQDNKLYQRVLWQLIRELCS  Ovis  aries  (sheep)
PRND_chi  ANQEELSREKQDNKLYQRVLWQLIRELCS  Capra  hircus  (goat)
PRND_bta  ANQEELSREKQDNKLYQRVLWQLIRELCS  Bos  taurus  (cow)
PRND_ttr  VNQEELSREKQDNSLYQRVLWQLIRELCS  Tursiops  truncatus  (dolphin)
PRND_ssc  ANQEE-SHEKPDNKLYQRVLWRLIRELCS  Sus  scrofa  (pig)
PRND_pcw  VNQEELSLEKPDNKLYQRVLWRLIRELCS  Physeter  catodon  (whale)
PRND_ban  ANQEEFSREKQDNKLHQRVLWRLIRELCS  Boreoeuthere  ancestralis  (boreoeuthere)
PRND_dno  ANQAELAHERQD-TLHGRVLGRLIRELCA  Dasypus  novemcinctus  (armadillo)
PRND_cho  ANQAEFSREKHD-KLHQRVLWRLIRELCS  Choloepus  hoffmanni  (sloth)
PRND_pcp  VNQEEFSREKQDNKLYQRILWRLIRELCS  Procavia  capensis  (hyrax)
PRND_ete  ANQAEFSAPQQDSRLHQRVLWRLIRELCS  Echinops  telfairi  (tenrec)
PRND_ema  ANQEEFSREKQDNKVYQRILWRLIRELCS  Elephas  maximus  (elephant)
PRND_laf  ANQEEFSR-KQDNKVYQRILWRLIRELCS  Loxodonta  africana  (elephant)
PRND_tma  ANQEEFSREKQDNKLYQRILWRLIRELCS  Trichechus  manatus  (manatee)
PRND_mdo  INKLEPLEEQNISDIYSRILEQLIKELCA  Monodelphis  domestica  (opossum)
PRND_meu  VNNLETLEEKNASDIHSRVLEQLIKELCA  Macropus  eugenii  (wallaby)
PRND_oan  ANRGELTAGGNASDVHVRVLLRLVEELCA  Ornithorhynchus  anatinus  (platypus)
PRND_aca  SNKLNLSKGKDLSNTKERVMWVLIHHLCA  Anolis  carolinensis  (lizard)
PRND_xtr RNKVWISQLEDDEEGDIYMSVATQVLQFLCM  Xenopus  tropicalis  (frog)
          ** * .  * *. ::*::**:* :* .:   
</pre>
Below 45 PRND doppel sequences from land vertebrates are provided. Most are complete and reliable, but others are fragmentary and no better than the ongoing genome project from which they were extracted (initially low coverage, perhaps a single applicable trace). The phylogenetic distribution is approximately half as extensive as for PRNP. Almost all species having an available PRND would also have an available PRNP. It would be very easy to extend PRND coverage since primer design for PCR presents no issues. All sequences consist of a single coding intron. The only rare genomic event for PRND of any phylogenetic depth is the indel shown above.


<pre>
However nothing prevents homoplasy of tandem duplications and indeed we shall see this in teleost fish. On the contrary, the observation that both copies of a given duplication can be useful over billions of year of branch length supports the likelihood of it happening again in a lineage not participating in the original duplication. Here lizard and frog doppel queries retrieve solely mammalian and turtle PRND genes when back-blasted against the GenBank non-redundant nucleotide division. Both lack the repeat region and retain some internal diagnostic doppel signatures though not the second disulfide bond. This argues against the idea of multiple independent duplications of the prion gene in lizard and frog distinct from a later lineage-specific duplication in mammals (with birds then never having a PRND to delete).
11 primates (Euarchonta)
7 glires (rodents and rabbits)
14 laurasiatheres
1 ancestral boreoeuthere
2 xenarthrans
5 aftrotheres
2 marsupial
1 platypus
0 bird
1 lizard
1 amphibian
</pre>


[[image:prnd_align.png|left|]]
The prion gene in teleost fish has radically diverged from its mammalian counterpart especially in the repeat region but remains recognizable via various conserved internal features, residual synteny, and its weak alignment. Fugu has a second PRNP gene on a different chromosome (presumably resulting from the whole genome duplication in Teleostei) plus an apparent novel tandem duplication that resembles PRNP rather than PRND. Coelocanth genome has been proposed but not begun -- that could further refine the timing of tetrapod PRND duplication.


<pre>
As it stands, that event occurred after teleost fish divergence but before that of amphibians, say 400 million years ago. The prion gene clearly represents the ancestral form and presumably ancestral function, ie, a doppel-like ancestor did not duplicate to a second gene that become PRNP. No counterpart of PRNP can be located in the initial release of the chondrichthyian genome, Callorhinchus milii, but that will soon be finished to higher coverage and regional assembly. PRNP is most likely an ancient gene that simply has become unrecognizable.
>PRND_hsa human full length
MRKHLSWWWLATVCMLLFSHLSAVQTRGIKHRIKWNRKALPSTAQITEAQVAENRPGAFIKQGRKLDIDFGAEGNRYY
EANYWQFPDGIHYNGCSEANVTKEAFVTGCINATQAANQGEFQKPDNKLHQQVLWRLVQELCSLKHCEFWLERGAGLRVTMHQPVLLCLLALIWLTVK*


>PRND_ptr Pan chimpanzee full length
Doppels are evolving noticeably faster than prions but have not become pseudogenes in any species investigated to date. (Very recent pseudogenes that have not yet acquired internal stop codons or loss of deeply invariant residues are difficult to detect.) It must be remembered that PRNP's globular region lies within the most slowly evolving quartile of mammalian genes. As a representative example, human/dog proteins have 78% identity for PRND but 87% for PRNP. A reconstructed ancestral mammal sequence for PRND shows no sign whatsoever of converging to a PRNP-like sequence, percent identity ancester-to-ancestor remains in the mid-20's. Since this uses up 100 million years of the 400 available, doppel may have evolved more drastically at an earlier time, perhaps soon after the duplication event.
MRKHLSWWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSTAQITEAQVAENRPGAFIKQGRKLDIDFGAEGNRYY
EANYWQFPDGIHYNGCSEANVTKEVFVTGCIHATQAANQGEF
QKPDNKLHQQVLWRLVRELCSLKHCEFWLERGAGLRVTMHQPVLLCLLAFIWLMVK*


>PRND_ggo gorilla
The most economical explanation of the data is that the slow evolving prion gene retains the lion's share of ancestral functions whereas doppel has a narrow new but possibly related function with limited and specialized expression in uncommon cell types, yet one important enough for longterm gene retention. Over longer evolutionary time spans, we can't be sure either gene really functions identically in all species.
MRKHLSWWWLATVCMLFFSHLSAVQARGIKHRIKWNRKALPSTAQITEAQVAENRPGAFIKQGRKLDIDFGAEGNRYY
EANYWQFPDGIHYNGCSEANVTKEVFVTGCINATQAANQGEF
HKPDNKLHQQVLWRLVRELCSLKHCEWLERSAGLRVTMHQPVLLCLLAFIWLMMK*


>PRND_ppy Pongo pygmaeus orangutan shares 2 bp deletion unique to primates.
To further investigate the co-evolution of PRNP and PRND, it is imperative to obtain additional pairs of gene sequences from a phylogenetically representative sample of species, which here means echidna, turtles, and more lizards and amphibians. PRNP tends to be over-sampled within Artiodactylia, especially Bovidae. Doppel remains very poorly represented at dbEST even in much-studied mammals with enriched libraries of tissues like testis where doppel is known to be transcribed. Consequently additional doppel sequences will not drop out as byproducts of transcriptome projects.
MKNHLSWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSTAQITEAPGAENRPGALSkQGR 
QLDIDFGTEGNRYYEANYWQFPDGIHYDGCSEANVTKEVFVTGCINATQAANQGEFQ
KPDNKLHQQVLWRLVQELCSLKHCEFWLERGAGLRVTMHQPVLLCLLAFIWLMVK*


>PRND_nle Nomascus leucogenys gibbon
However a respectable number of doppel sequences have accumulated. In addition to genome projects, van Rheede and coworkers sequenced nine doppels from important early diverging clades of placental mammals. PRND from the chimpanzee genome has special interest for evaluating known human doppel polymorphisms to determine "wildtype" human. Macaque doppel also exhibits the 2 amino acid deletion seen in human at position 122-123, showing this event predated old world monkey divergence. In fact that event can be precisely timed to the stem lying between tarsier and new world monkey divergence and shown highly non-homoplasic.
MRKHLSWWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSTAQITEAQVAENRPGGFIKQGRKLDIDFGAEGNRYY
EANYWQFPDGIHYDGCSEANVTKEVFV
TGCINATQAANQGEFQKPDNKLHQRVLWRLVRELCSLKRCEFWLERGAGLRVTMHQPVLLCLLAFIWLMVK*


>PRND_pha Papio hamadryas (baboon)
=== Ancestral length and PRND indels ===
        WLSRLHAAPQ HLSLVVQARGIKHRIKWNRKALPSTAQITEAQVAENPPGSFIKQGRKLNIDFGAEGNRYY
EANYWQFPDGIHYDGCSEANVTKEVFVTGC
INATQAANQGEFQKPDNKLHQRVLWRLVQELCSLKRCEFWLEGGAGLRVTMHQPVLLCLPAFVWLMVK*


>PRND_mml Macaca mulata full length from trace archives
Here an interesting loss of 2 residues helps define primates from new world monkeys on. Other indels in this region have limited phylogenetic interest because of homoplasy -- support for a hedgehog and shrew sister relation to the exclusion of other laurasiatheres is undercut by similar deletion in kangaroo rat, mouse lemur and pika.
MRQHLSRWWLATVCMLLLSHLSVVQARGIKHRIKWNRKALPSTAQITEAQVAENRPGAFIKQGR
KLNIDFGAEGNRYYEANYWQFPDGIHYDGCSEANVTKEVFVTGCINATQAENQGEFQK
<font color="blue">prnd_hsa anqgefq--kpdnklhqqvlwrlvqelcs  homo sapiens (human)
PDNKLHQRVLWRLVQELCSLKRCEFWLERGAGLRVTMHQPVLLCLPAFVWLMV*
prnd_ptr anqgefq--kpdnklhqqvlwrlvrelcs  pan troglodytes (chimp)
prnd_ggo anqgefh--kpdnklhqqvlwrlvrelcs  gorilla gorilla (gorilla)
prnd_ppy anqgefq--kpdnklhqqvlwrlvqelcs  pongo pygmaeus (orang_sumatran)
prnd_nle anqgefq--kpdnklhqrvlwrlvrelcs  nomascus leucogenys (gibbon)
prnd_mml enqgefq--kpdnklhqrvlwrlvqelcs  macaca mulatta (rhesus)
prnd_pha anqgefq--kpdnklhqrvlwrlvqelcs  papio hamadryas (baboon)
prnd_cja anqaefq--kpdnklhqrvlwrlvqelcs  callithrix jacchus (marmoset_nwm)</font>
prnd_tsy anaaerprearddplhqrvlgrlvrelcs  tarsius syrichta (tarsier)
prnd_oga anqaefsrekqdnklhqrilwrlirelcs  otoleumur garnetti (bushbaby)
<font color="brown">prnd_mmr anqaefarekqd-klherilwrltrelcs  microcebus murinus (mouse_lemur)</font>
prnd_tbe anqaefskekqdnklyqrvlwrlikelcs  tupaia belangeri (tree_shrew)
prnd_ocu anqgefsrekqdnklhqrvlwrlikelcs  oryctolagus cuniculus (rabbit)
<font color="brown">prnd_opr anqgefsrekq-nklhqrvlwrlikelcs  ochotona princeps (pika)
prnd_dor anqaefaremqd-kfyqrvlwrltkelca  dipodomys ordii (kangaroo_rat)</font>
prnd_str anqaefsrekqdnklhqrvlwrlikelcs  spermophilus tridecemlineatus (ground_squirrel)
prnd_rno anqaefsrekqdsklhqrvlwrlikeics  rattus norvegicus (rat)
prnd_mmu anqaefsrekqdsklhqrvlwrlikeics  mus musculus (mouse)
prnd_cpo anqaefsrekqdnklhqrilwrlikelcs  cavia porcellus  (guinea_pig)
<font color="blue">prnd_sar anqeelsrekhd-klyqrvlwrlvrelcs  sorex araneus (shrew)
prnd_eeu anqeelsrekhd-klyqrvlwrlvrelcs  erinaceus europaeus (hedgehog)</font>
prnd_cfa anqeelsrekqdnklhqrvlwrlirelcs  canis familiaris (dog)
prnd_fca anqeelsrekqddklyqrvlwrlnr-ecs  felis catus (cat)
prnd_tte enqeelsrekqddklhqrilwrlirelcs  tapirus terrestris (tapir)
prnd_eca anqeelsqekqddklyqrilwrliselcs  equus caballus (horse)
prnd_mlu anqeelsqerpdnrlhrrilwrlvrelcs  myotis lucifugus (microbat)
prnd_csp vnqeelsqekqdkllhqrilwqlirelcs  cynopterus sphinx (bat)
prnd_oar anqeelsrekqdnklyqrvlwqlirelcs  ovis aries (sheep)
prnd_chi anqeelsrekqdnklyqrvlwqlirelcs  capra hircus (goat)
prnd_bta anqeelsrekqdnklyqrvlwqlirelcs  bos taurus (cow)
prnd_ttr vnqeelsrekqdnslyqrvlwqlirelcs  tursiops truncatus (dolphin)
prnd_ssc anqee-shekpdnklyqrvlwrlirelcs  sus scrofa (pig)
prnd_pcw vnqeelslekpdnklyqrvlwrlirelcs  physeter catodon (whale)
prnd_ban anqeefsrekqdnklhqrvlwrlirelcs  boreoeuthere ancestralis (boreoeuthere)
<font color="blue">prnd_dno anqaelaherqd-tlhgrvlgrlirelca  dasypus novemcinctus (armadillo)
prnd_cho anqaefsrekhd-klhqrvlwrlirelcs  choloepus hoffmanni (sloth)</font>
prnd_pcp vnqeefsrekqdnklyqrilwrlirelcs  procavia capensis (hyrax)
prnd_ete anqaefsapqqdsrlhqrvlwrlirelcs  echinops telfairi (tenrec)
prnd_ema anqeefsrekqdnkvyqrilwrlirelcs  elephas maximus (elephant)
prnd_laf anqeefsr-kqdnkvyqrilwrlirelcs  loxodonta africana (elephant)
prnd_tma anqeefsrekqdnklyqrilwrlirelcs  trichechus manatus (manatee)
prnd_mdo inklepleeqnisdiysrileqlikelca  monodelphis domestica (opossum)
prnd_meu vnnletleeknasdihsrvleqlikelca  macropus eugenii (wallaby)
prnd_oan anrgeltaggnasdvhvrvllrlveelca  ornithorhynchus anatinus (platypus)
prnd_aca snklnlskgkdlsntkervmwvlihhlca  anolis carolinensis (lizard)
prnd_xtr rnkvwisqleddeegdiymsvatqvlqflcm xenopus tropicalis (frog)


>PRND_cja Callithrix jacchus 1st new world monkey 89% 
=== Phylogenetic distribution of available PRND sequences ===
MRKHLSGWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSAAQITEAQVAENRPGTFIKQGRKLDINFGAEGNRYY
EANYWQLPDGIHYDGCSETNVTKEVFVTGCINATQAANQAEFQKPDNKLHQRVLWRLVQELCSLKRCEFWLERGAGFRVATHQPLLLCLLAFIWLMAK*


>PRND_tsy Tarsius syrichta tarsier
11 primates (euarchonta)
MRKPLGGWRLAVVCVLLLGLLSAARARGIKHRFKWNRKASPSAARVTEARVAESRPGAFIRRGRKLDIDFGAEGNKYY
  7 glires (rodents and rabbits)
EANYWQFPDGIHYDGCSKANVTKELLVAGCINATHAANAAERPREARDDPLHQRVLGRLVRELCSAKHCDFWPERAAAPGTARARPGALLLVSRL
16 laurasiatheres
  1 ancestral boreoeuthere
  2 xenarthrans
  5 aftrotheres
  2 marsupials
  1 platypus
  0 bird (gene deleted in chicken and finch)
  1 lizard
  1 amphibian


>PRND_mmr Microcebus murinus
=== Reference collection of PRND sequences ===
GNRYYEANYWQFPDGIHYDGCSDANVTKEVFVASCINATVAANQAEFAREKQDKLHERILWRLTRELCSVKRCEFWLERGAGLRVAEDCPTILSLLLLLWLLLR*


>PRND_tbe Tupaia belangeri tree shrew 6.7 m tr frag
Below 45 PRND doppel sequences from land vertebrates are provided. Most are complete and reliable, but others are fragmentary and no better than the ongoing genome project from which they were extracted (initially low coverage, perhaps a single applicable trace). The phylogenetic distribution is approximately half as extensive as for PRNP. Almost all species having an available PRND would also have an available PRNP. It would be very easy to extend PRND coverage since primer design presents no issues. The most interesting rare genomic event for PRND of any phylogenetic depth is the indel shown above.
RALPSTAHITEARVAENRPGAFIRQGRKLDIDFGVEGNRYYEANYWQFPDGIHYDGCSEVNVTKEMFITSCINATQA
ANQAEFSKEKQDNKLYQRVLWRLIKELCSIKHCDFWLERGAGLRVTMHLPVMLCLLVFVWFVVK*


>PRND_mmu Mus musculus mouse full length
>PRND_homSap Homo sapiens (human) full
MKNRLGTWWVAILCMLLASHLSTVKARGIKHRFKWNRKVLPSSGGQITEARVAENRPGAF
MRKHLSWWWLATVCMLLFSHLSAVQTRGIKHRIKWNRKALPSTAQITEAQVAENRPGAFIKQGRKLDIDFGAEGNRYYEANYWQFPDGIHYNGCSEANVTKEAFVTGCINATQAANQGEFQKPDNKLHQQVLWRLVQELCSLKHCEFWLERGAGLRVTMHQPVLLCLLALIWLTVK*
IKQGRKLDIDFGAEGNRYYAANYWQFPDGIYYEGCSEANVTKEMLVTSCVNATQAANQAE
FSREKQDSKLHQRVLWRLIKEICSAKHCDFWLERGAALRVAVDQPAMVCLLGFVWFIVK*
>PRND_ptanTro Pan trogdylotes (chimpanzee) full
MRKHLSWWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSTAQITEAQVAENRPGAFIKQGRKLDIDFGAEGNRYYEANYWQFPDGIHYNGCSEANVTKEVFVTGCIHATQAANQGEFQKPDNKLHQQVLWRLVRELCSLKHCEFWLERGAGLRVTMHQPVLLCLLAFIWLMVK*
>PRND_gorGor Gorilla gorilla (gorilla)
MRKHLSWWWLATVCMLFFSHLSAVQARGIKHRIKWNRKALPSTAQITEAQVAENRPGAFIKQGRKLDIDFGAEGNRYYEANYWQFPDGIHYNGCSEANVTKEVFVTGCINATQAANQGEFHKPDNKLHQQVLWRLVRELCSLKHCEWLERSAGLRVTMHQPVLLCLLAFIWLMMK*
>PRND_ponPyg Pongo pygmaeus (orangutan) shares 2 bp deletion unique to primates.
MKNHLSWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSTAQITEAPGAENRPGALSkQGRQLDIDFGTEGNRYYEANYWQFPDGIHYDGCSEANVTKEVFVTGCINATQAANQGEFQKPDNKLHQQVLWRLVQELCSLKHCEFWLERGAGLRVTMHQPVLLCLLAFIWLMVK*
>PRND_nomLeu Nomascus leucogenys (gibbon)
MRKHLSWWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSTAQITEAQVAENRPGGFIKQGRKLDIDFGAEGNRYYEANYWQFPDGIHYDGCSEANVTKEVFVTGCINATQAANQGEFQKPDNKLHQRVLWRLVRELCSLKRCEFWLERGAGLRVTMHQPVLLCLLAFIWLMVK*
>PRND_papHam Papio hamadryas (baboon)
MRKHLSWWWLATVCMLLFSHLSAVQTRGIKHRIKWNRKALPSTAQITEAQVAENRPGAFIKQGRKLDIDFGAEGNRYYEANYWQFPDGIHYNGCSEANVTKEAFVTGCINATQAANQGEFQKPDNKLHQQVLWRLVQELCSLKHCEFWLERGAGLRVTMHQPVLLCLLALIWLTVK*
>PRND_macMul Macaca mulata (macaque) full
MRQHLSRWWLATVCMLLLSHLSVVQARGIKHRIKWNRKALPSTAQITEAQVAENRPGAFIKQGRKLNIDFGAEGNRYYEANYWQFPDGIHYDGCSEANVTKEVFVTGCINATQAENQGEFQKPDNKLHQRVLWRLVQELCSLKRCEFWLERGAGLRVTMHQPVLLCLPAFVWLMV*
>PRND_calJac Callithrix jacchus (marmoset) new world monkey 89%
MRKHLSGWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSAAQITEAQVAENRPGTFIKQGRKLDINFGAEGNRYYEANYWQLPDGIHYDGCSETNVTKEVFVTGCINATQAANQAEFQKPDNKLHQRVLWRLVQELCSLKRCEFWLERGAGFRVATHQPLLLCLLAFIWLMAK*
>PRND_tarSyr Tarsius syrichta (tarsier)
MRKPLGGWRLAVVCVLLLGLLSAARARGIKHRFKWNRKASPSAARVTEARVAESRPGAFIRRGRKLDIDFGAEGNKYYEANYWQFPDGIHYDGCSKANVTKELLVAGCINATHAANAAERPREARDDPLHQRVLGRLVRELCSAKHCDFWPERAAAPGTARARPGALLLVSRL
>PRND_micMur Microcebus murinus (mouse_lemur)
MRKHLGGWRPAIVFILLFSHLAVVKARGIKHRIKWNRKPLPSTVHITEALVAENRPGAFIKQGRKLDVDFGEEGNRYYEANYWQFPDGIHYDGCSDANVTKEVFVASCINATVAANQAEFAREKQDKLHERILWRLTRELCSVKRCEFWLERGAGLRVAEDCPTILSLLLLLWLLLR*
>PRND_tupBel Tupaia belangeri tree shrew 6.7 m tr frag
RALPSTAHITEARVAENRPGAFIRQGRKLDIDFGVEGNRYYEANYWQFPDGIHYDGCSEVNVTKEMFITSCINATQAANQAEFSKEKQDNKLYQRVLWRLIKELCSIKHCDFWLERGAGLRVTMHLPVMLCLLVFVWFVVK*
>PRND_musMus Mus musculus (mouse) full
MKNRLGTWWVAILCMLLASHLSTVKARGIKHRFKWNRKVLPSSGGQITEARVAENRPGAFIKQGRKLDIDFGAEGNRYYAANYWQFPDGIYYEGCSEANVTKEMLVTSCVNATQAANQAEFSREKQDSKLHQRVLWRLIKEICSAKHCDFWLERGAALRVAVDQPAMVCLLGFVWFIVK*
>PRND_ratNor Rattus norvegicus (rat) full  
MKNRVGTWGLAILCLLLASHLSTVKARGIKHRFKWNRKVLPSSGQITEAQVAENRPGAFIKQGRKLDIDFGAEGNKYYAANYWQFPDGIYYEGCSEANVTKEVLVTRCVNATQAANQAEFSREKQDSKLHQRVLWRLIKEICSTKHCDFWLERGAALRITVDQQAMVCLLGFIWFIVK*
>PRND_cavPor Cavia porcellus (guinea pig) fragment AY130773 N-extended at traces 7,499,469 seq
MKTSLCVWALVCVLLQCHFSSVAARGIKHRIRWGRKPTPSPSQVTEARVAMTRPGAFIKEGHKLNIDFGAEGNRYYETNYWQFPDGIHYNGCSDTNVTKEVLVTSCINATQAANQAEFSREKQDNKLHQRILWRLIKELCSA
>PRND_dipOrd Dipodomys ordii (squirrel) pseudogene
ITEARYRENAQGPSSIKP--QADIDF--ERAQ*YEA*YWQFADGINYEGCSRRHVTKQMFVSRCINVTQAANQAEFAREMQD-KFYQRVLWRLTKELCAVKQCDFWLERGEGCPVAIVNRPAMLGLLLCMWFIL
>PRND_speTri Spermophilus tridecemlineatus (squirrel) full
MKKHLGTWGLAVVCVLLSTHLSAIKARGIKHRIKWNRKSVPSTVQITEAQVAQNPPGAFIKQGRKLHIDFGAEGNKYYEANYWQFPDGIYYDGCSEANVTKEVFIAKCINATQAANQAEFSREKQDNKLHQRVLWRLIKELCSVKHCDFWLEGGAGFQLSVDQPVMLCLLVFIWLMVK*
>PRND_oryCun Oryctolagus cuniculus (rabbit) revised complete from traces 8,968,713 sequences 75%
MRKHLGAWGLAIVCVLLFSHLPPAKARGIKHRIKWNRKALPSTAQITEAHVAENRPGTFIRQGRKLNIDFGPEGNKYYEANYWQFPDGVHYDGCSEGNVTKEAFVAKCVNATQAANQGEFSREKQDNKLHQRVLWRLIKELCSIKHCDFWLERGAGVQVGGEQPLVLGLLLCTWLLVK*
>PRND_ochPri Ochotona princeps (pika) full
MRKHLGGWGLAIVCVLLFSLLPTVKARGIKHRIKWNRKALPSTAQITEARVAENRPGTFIRQGQKLSIDFGPEGNKYYEANYWQFPDGIHYDGCSEGNVTKEVFVAKCINATQAANQGEFSREKQNKLHQRVLWRLIKELCSIKHCDFWLERGAGFPVTVGQPMVVLCLLIFTWVLVK*
>PRND_canfam Canis familiaris (dog) full
MRKHLGGCWLAIVCVLLLSQLSAVEARGIKHRIKWNRKALPGTSQVTEARSAEIRPGAFIRQGRKLDIDLGPEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTGCINATQVANQEELSREKQDNKLHQRVLWRLIRELCSVKRCDFWLERGAGPRVAGAQPVLLCLLAFIWFIVK*
>PRND_ailMel Ailuropoda melanoleuca (panda) full 89% identical dog
MRKHLGGCWLAIVCVLLFSQLSAVKARGIKHRIKWNRKALPSTSQVTEARTAEIRPGAFIRQGRKLDIDLGAEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVSGCINATRVANQEELSREKQDNRLYQRVLWRLVRELCSVKHCDFWLERGAGLRVGGDQALLLCLLVFIWFIVK*
>PRND_felCat Felis catus (cat) improved fragment 8,248,053 traces now 9.2
MRKHLGGCWLAIVCVLLFSQLSAVKARGIKHRIKWNRKTLPSISQVTEAHTAEIRPGAFIRQGRKLDIDLGAEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTSCINATQVANQEELSREKQDhKLYQRVLWRLNREALLWSAHGNFGRERG
>PRND_equCab Equus caballus (horse)
MRKHLGGCCLAIVCVLLFSQLPVVLSRGTKHRIKWNRKALPSTAKVTEARVEEIRPGAFIRQGRKLNINFGAEGNRYYEANYWQFPDEIHYNGCSEANVTKEKFVISCINATQEANQEELSQEKQDDKLYQRILWRLISELCSVKHCDFGLESGTGLRVTMDQPVLLCLLVFIWFIVK*
>PRND_tapTer Tapirus terrestris (tapir) fragment
KALPSTSKVTEAHTAEIRPGAFIRQGRKLNIDFGAEGNRYYEANYWQFPDEIHYNGCSEANVTKEKFVISCINATQAENQEELSREKQDDKLHQRILWRLIRELCSV
>PRND_sorAra Sorex araneus (shrew) Laurasiatheria; Insectivora 7.23M tr
MRKHLGWCLAIACVLLLCQVPAAQARGIKHRIKWGRKAPPSTPQVTEARVAEIRPGAFIRQGRKLNLNLGGEDKRYYDAYYWQFPDGIHYNGCSSANVTREKFISGCINATRAANQEELSREKHDKLYQRVLWRLVRELCSLKRCDFWSERGAGLQVTVDQLMMFCLLAFTWFIMK*  
   
   
>PRND_rno Rattus norvegicus rat full length
>PRND_eriEur Erinaceus europaeus (hedgehog)10,952,642 seq complete
MKNRVGTWGLAILCLLLASHLSTVKARGIKHRFKWNRKVLPSSGQITEAQV
MRKHLGGWWLAIVCVLFFSQLSAVKARGIKHRFKWNRKALPSTNHVTEAQVSEIRPGAFIRQGTKLDIDLGAEANRYYEANYWQFPDGIHYNGCSEVNVTKAKFIASCINATHSANQEELSREKHDKLYQRVLWRLVRELCSLKRCDFWSERGAGLQVTVDQLMMFCLLAFTWFIMK*
AENRPGAFIKQGRKLDIDFGAEGNKYYAANYWQFPDGIYYEGCSEANVTKEVLVTRCVNA
TQAANQAEFSREKQDSKLHQRVLWRLIKEICSTKHCDFWLERGAALRITVDQQAMVCLLGFIWFIVK*
  >PRND_myoLuc Myotis lucifugus (microbat) full
 
MRKQLGGCCLAIVCVLLFSQLAAVQARGIKHRIKWNRKGAAPPSSSQVTEAQRVEMQLRPGAFIKHGRKLDIDFGAEANRYYEANYWQFPDEIHYNGCSSEANVTREKFVSGCINATQAANQEELSQERPDNRLHRRILWRLVRELCSVKHCDFWLENGAGLWVTVHRPVMPCLLVSIWFIVK*
>PRND_cpo Cavia porcellus (guinea pig) fragment AY130773 N-extended at traces 7,499,469 seq
MKTSLCVWALVCVLLQCHFSSVAARGIKHRIRWGRKPTPSPSQVTEARVAMTRPGAFIKEGHKLNIDFGAEGNRYYETNYWQFPDGIHYNGCSDT
>PRND_pteVam Pteropus vampyrus (macrobat) frameshifts frag
NVTKEVLVTSCINATQAANQAEFSREKQDNKLHQRILWRLIKELCSA
MRRQLGGCWLAIVCVLLFSQLSTVKARGIKHRTKWNR PCDRVS VTESQ GAFIKQGRK
 
>PRND_dor Dipodomys ordii pseudogene
>PRND_cynSph Cynopterus sphinx (bat) fragment
ITEARYRENAQGPSSIKP--QADIDF--ERAQ*YEA*YWQFADGINYEGCSRRHVTKQMF
KTLPSPSSHVTESQTAEMRPGAFVKQGRKLNIDFGDEGNRYYEAHYWEFPDGIYYDACSKANVTKEKFVTSCINATQAVNQEELSQEKQDKLLHQRILWQLIRELCSV
VSRCINVTQAANQAEFAREMQD-KFYQRVLWRLTKELCAVKQCDFWLERGEGCPVAIVNR
PAMLGLLLCMWFIL
>PRND_bosTau Bos taurus (cow) full  
 
MRKHLGGCWLAIVCILLFSQLCSVKARGIKHRIKWNRKVLPSTSQVTEARTAEIRPGAFIKQGRKLDIDFGVEGNRYYEANYWQFPDGIHYNGCSKANVTKEKFITSCINATQAANQEELSREKQDNKLYQRVLWQLIRELCSTKHCDFWLERGAGLRVTLDQPMMLCLLVFIWFIVK*
>PRND_str Spermophilus tridecemlineatus ground squirrel complete tr
MKKHLGTWGLAVVCVLLSTHLSAIKARGIKHRIKWNRKSVPSTVQITEAQVAQNPPGAF
>PRND_oviAri Ovis aries (sheep) full  
IKQGRKLHIDFGAEGNKYYEANYWQFPDGIYYDGCSEANVTKEVFIAKCINATQAANQAE
MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKVLPSTSQVTEAHTAEIRPGAFIKQGRKLDINFGVEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTSCINATQVANQEELSREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLQVTLDQPMMLCLLVFIWFIVK*
FSREKQDNKLHQRVLWRLIKELCSVKHCDFWLEGGAGFQLSVDQPVMLCLLVFIWLMVK*
 
>PRND_capHir Capra hircus (goat)
>PRND_ocu Oryctolagus cuniculus rabbit revised complete from traces 8,968,713 sequences 75%
MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKVLPSTSQVTEAHTAEIRPGAFIKQGRKLDINFGVEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTSCINATQVANQEELSREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLQVTLDQPMMLCLLVFIWFIVK*
MRKHLGAWGLAIVCVLLFSHLPPAKARGIKHRIKWNRKALPSTAQITEAHVAENRPGTFI
RQGRKLNIDFGPEGNKYYEANYWQFPDGVHYDGCSEGNVTKEAFVAKCVNATQAANQGE
>PRND_conTau Connochaetes taurinus (wildebeest) EF192574
FSREKQDNKLHQRVLWRLIKELCSIKHCDFWLERGAGVQVGGEQPLVLGLLLCTWLLVK*
MRKHLGGCWLAIVCVLLFSHLSSVKARGIKHRIKWNRKVLPSTSQVTEARTAEIRPGAFIKQGRKLDIDFGVEGNRYYEANYWQFPDGIHYNGCSEPNVTKENFITSCINATQVANQEEMSREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLQVTLDQPMMLCLLVFIWFIVK*
 
>PRND_opr Ochotona princeps pika complete
>PRND_girCam Giraffa camelopardalis (giraffe) EF192572
MRKHLGGWGLAIVCVLLFSLLPTVKARGIKHRIKWNRKALPSTAQITEARVAENRPGTFIRQGQKLSIDFGPEGNKYY
MRKHLGRCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKVLPSTSQVTEAHTAEIRPGAFIKQGRKLDIDFGVEGNRYYEANYWQFPDGIHYNGCSEANVTKEEFVTSCINATQAANQEELSREKQDNKLYQRILWRLIRELCSIKHCDFWLERGAGLQVTLDQPMMLCLLVFIWFIVK*
EANYWQFPDGIHYDGCSEGNVTKEVFVAKCINATQAANQGEFSREKQNKLHQRVLWRLIKELCSIKHCDFWLERGAGFPVTVGQPMVVLCLLIFTWVLVK*
 
>PRND_ama Antidorcas marsupialis (springbok) Bovidae; Antilopinae
>PRND_cfa Canis familiaris dog full length
MRKHLGGCWLAIACILLFSQLSSVKARGIKHRIKWNRKVLPSTSQVTEAHTAEIRPGAFIKQGRKLDIDFGVEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTSCINATQVANQEELSREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLRVTLDQPMMLCLLVFIWFIVK*
MRKHLGGCWLAIVCVLLLSQLSAVEARGIKHRIKWNRKALPGTSQVTEARSAEIRPGAFI
RQGRKLDIDLGPEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTGCINATQVANQEEL
>PRND_turTru Tursiops truncatus (dolphin)
SREKQDNKLHQRVLWRLIRELCSVKRCDFWLERGAGPRVAGAQPVLLCLLAFIWFIVK*
MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKALPSTSQVTEAHTAEIRPGAFIRQGRKLDINFGAEGNRYYEANYWQLPDGIHYNGCSEANVTKEKFVTSCINATQAVNQEELSREKQDNSLYQRVLWQLIRELCSNKQCDFWLERGAGLRVTLDQPMMLCLLVFIWFIVK* 
 
>PRND_pseCra Pseudorca crassidens (false killer whale) AP009417
>PRND_fca Felis catus cat improved fragment 8,248,053 traces now 9.2
MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKALPSTSQVTEAHTAEIRPGAFIRQGRKLDINFGAEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTSCINATQAVNQEELSREKQDNNLYQRVLWQLIRELCSNKQCDFWLERGAGLRVTLDQPMMLCLLVFIWFIVK*  
MRKHLGGCWLAIVCVLLFSQLSAVKARGIKHRIKWNRKTLPSISQVTEAHTAEIRPGAFIRQGRKLDIDLG
AEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTSCINATQVANQEELSREKQDhKLYQRVLWRLNREALLWSAHGNFGRERG
>PRND_phyCat Physeter catodon (sperm) whale middle fragment
 
KALPSTSQVTEAHTAEIVPGAFIKQGRKLDIDFGAEGNRYYEANYWQFPDGIHYNGCSEASVTKEKFVTSCINATQEVNQEELSLEKPDNKLYQRVLWRLIRELCSI
>PRND_eca Equus caballus perissodactyl
MRKHLGGCCLAIVCVLLFSQLPVVLSRGTKHRIKWNRKALPSTAKVTEARVEEIRPGAF
>PRND_susScr Sus scrofa (pig) full length ti|470951185  
IRQGRKLNINFGAEGNRYYEANYWQFPDEIHYNGCSEANVTKEKFVISCINATQEANQEE
MRKHLGGRRWAIVCILLFSQLSEVKARGIKHRIKWNRKALPSTSQVTEAHTAEMRPGAFIKQGRKLDIDFGAEGNRYYEANYWRFPDGIHYNGCSEVNVTKEKFVTSCINTTQAANQEESHEKPDNKLYQRVLWRLIRELCSIKHCDFWLERGAGLRVTMDQPMMLCLLVFIWLIVK*
LSQEKQDDKLYQRILWRLISELCSVKHCDFGLESGTGLRVTMDQPVLLCLLVFIWFIVK*
 
>PRND_lamPac Lama pacos (alpaca) wgs frag
>PRND_tte Tapirus terrestris (Brazilian tapir) perissodactyl fragment
MRKHLGGCWLALACVLLLSPLSAVKARGIKHRIRWNRRPLPSASQATEAYTAELRPG
KALPSTSKVTEAHTAEIRPGAFIRQGRKLNIDFGAEGNRYYEANYWQFPDEIHYNGCSEA
NVTKEKFVISCINATQAENQEELSREKQDDKLHQRILWRLIRELCSV
>PRND_borAnc Boreoeuthere ancestralis (ancestral)
 
MRKHLGAWWLAIVCILLFSHLSTVKARGIKHRIKWNRKALPSTAQVTEAHVAEIRPGAFIRQGRKLDIDFGAEGNRYYEANYWQFPDGIHYNGCSEANVTKEMFVTSCINATQAANQEEFSREKQDNKLHQRVLWRLIRELCSIKHCDFWLERGAGLRVTLDQPVMLCLLVFIWFMVK*
>PRND_mlu Myotis lucifugus traces ti|983665423 complete
MRKQLGGCCLAIVCVLLFSQLAAVQARGIKHRIKWNRKGAAPPSSSQVTEAQRVEMQLRP
>PRND_dasNov Dasypus novemcinctus (armadillo) pseudo frag
GAFIKHGRKLDIDFGAEANRYYEANYWQFPDEIHYNGCSSEANVTREKFVSGCINATQAA
  ANYWQLPDGILYDGCAEANVTKEALVAGCVNGHTAANQAELAHERQDTLHGRVLGRLIRELCALKRCKFWPDR
NQEELSQERPDNRLHRRILWRLVRELCSVKHCDFWLENGAGLWVTVHRPVMPCLLVSIWFIVK*
 
>PRND_dasNov Dasypus novemcinctus (armadillo)
>PRND_pva Pteropus vampyrus frameshifty frag
MRKHLGGWRLAIVCVLLSGHLSMVKARGIKHRIKWNRKAAPGAAQVTEARVAEQRPGAFVRQGRRLDIDFGAEGNRYYEANYWQLPDGILYDGCAEANVTKEALVAGCVNATQLANQAELAHEGQDTLHRRVLGRLIRELCALKRCKFWPDRAAGPRLVRGAPVFGGLLLLIWLLVR*
MRRQLGGCWLAIVCVLLFSQLSTVKARGIKHRTKWNR PCDRVS VTESQ GAFIKQGRK
 
>PRND_choHof Choloepus hoffmanni (sloth) single trace old dasypus pseudogene, ti|563245674
>PRND_csp Cynopterus sphinx bat Laurasiatheria; Chiroptera fragment
MRKHLGGWWLAAVFVLLVCHLSVAKARGIKHRIKWNRKALPSAAQVTEARIAESRPGAFIKQGRKLDIDFGAEGNKYYEANYWQFPDGIHYDGCSEANVTKEVFVTGCINATQAANQAEFSREKHDKLHQRVLWRLIRELCSVKHCDFWLERGGGLRLTVDQPVVSACWFHLAYRE*
KTLPSPSSHVTESQTAEMRPGAFVKQGRKLNIDFGDEGNRYYEAHYWEFPDGIYYDACSKANVTKEK
FVTSCINATQAVNQEELSQEKQDKLLHQRILWQLIRELCSV
>PRND_losAfr Loxodonta africana (elephant) Afrotheria 176 aa revised/corrected
 
MRKHLGAWWLAIAFVLLLSHLSMVTARGIKHRIKWNRKALPNTGHVTAAQVTETRPGAFIRHGRKLDIDFGAEGNRYYEANYWQFPDGIHYDGCSEANVTKEMFVTSCINTTQAANQEEFSRKQDNKVYQRILWRLIRELCSVKHCDFWLDRGGGLRVSLDQPVMLCLLVFIWFMVK*
>PRND_bta Bos taurus cow full length
MRKHLGGCWLAIVCILLFSQLCSVKARGIKHRIKWNRKVLPSTSQVTEARTAEIRPGAFI
>PRND_eleMax Elephas maximus (elephant) Afrotheria fragment
KQGRKLDIDFGVEGNRYYEANYWQFPDGIHYNGCSKANVTKEKFITSCINATQAANQEEL
  KALPNTGHVTAAQVTETRPGAFIRHGRKLDIDFGAEGNRYYEANYWQFPDGIHYDGCSEANVTKEMFVTSCINTTQAANQEEFSREKQDNKVYQRILWRLIRELCSV
SREKQDNKLYQRVLWQLIRELCSTKHCDFWLERGAGLRVTLDQPMMLCLLVFIWFIVK*
 
>PRND_proCap Procavia capensis (cape rock hyrax) Afrotheria fragment AY130772 ti|1293358170
>PRND_oar Ovis aries sheep full length
KPVTNPAHMTAAQVSDRRLGTFIRHGRKLDIDFGAEGNRYYEANYWLFPDGIHYDGCSDTNVTKELFVTNCINTTQAVNQEEFSREKQDNKLYQRILWRLIRELCSllglDFWPERVGGLffSLDQPVMLCLLVFIWFMLK*
MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKVLPSTSQVTEAHTAEIRPGAFI
KQGRKLDINFGVEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTSCINATQVANQEEL
>PRND_echTel Echinops telfairi (tenrec) Afrotheria 10,323,158 seq
SREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLQVTLDQPMMLCLLVFIWFIVK*
MRKHLGAGWLALACVLLFGHLSVVPARGIKHRIKWNRKTLPSTAHVTEARVSVTRPGAFVRHGQKLDVDLGADGNRYYEAHYWQFPDGIHYDGCSDANVTREMLVTRCINATQAANQAEFSAPPRDQQDSRLHQRVLWRLIRELCSAKRCDFWLEGAGASRAGLDQPPVLLGLLVLLGLTVK*
 
>PRND_chi Capra hircus (goat)
>PRND_triMan Trichechus manatus (manatee) Afrotheria fragment
MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKVLPSTSQVTEAHTAEIRPGAFIKQGRKLDINFGV
KPLPNTPHVTAAQVSDARPGAFIRHGRKLDIDFGAEGNRYYEANYWQFPDGIHFDGCSEANVTKEMFVTSCINTTQAANQEEFSREKQDNKLYQRILWRLIRELCSV
EGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTSCINATQVANQEELSREKQDNKLYQRVLWQLIREL
CSIKHCDFWLERGAGLQVTLDQPMMLCLLVFIWFIVK*
>PRND_monDom Monodelphis domestica (opossum) doppel genomic revised +rassf2 -prnd -prnp
 
MRRHLGICWIAIFFALLFSDLSLVKAKTTRQRNKSNRKGLQTNRTNPTTVQPSEKLQGTFIRNGRKLVIDFGEEGNSYYATHYSLFPDEIHYAGCAESNVTKEVFISNCVNATRVINKLEPLEEQNISDIYSRILEQLIKELCALNYCEFRTGKGTGLRLSLDQYVMVYLVILTCLIVK*
>PRND_ama Antidorcas marsupialis (springbok) Bovidae; Antilopinae
MRKHLGGCWLAIACILLFSQLSSVKARGIKHRIKWNRKVLPSTS
>PRND_macEug Macropus eugenii (wallaby)
QVTEAHTAEIRPGAFIKQGRKLDIDFGVEGNRYYEANYWQFPDGIHYNGCSEANVTKE
MRRHLGTWWTAIFFALLFSDLSLVKAKGTRQRNKSNRKSLQTNRVNPTTAQPSEILQGAFIRQGRKLSIDFGEEGNSYYETHYQLFPDEIHYVGCTESNVTKDIFISNCMNATHAVNNLETLEEKNASDIHSRVLEQLIKELCALKYCELETETGAGLKLSLDQSVMVYLVILTCLIVK*
KFVTSCINATQVANQEELSREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLRVT
LDQPMMLCLLVFIWFIVK*
>PRND_sacHar Sarcophilus harrisii (tasmanian_devil) single exon gene 77% macEug
 
MRTPLETWWIAIFFTLLFSDLSLVKAKGIRQRNKSNRKSLQTNRANPTREQPSKILQGTFIRKGRKLSINFGEEGNSYYEAHYKLFPDEIHYVGCAESSVTKDVFISNCVNVTHTANKLEPPEERNSSAIYSRVLEQLIKELCALKYCEFGMQIGAGFRLSLDQSMMVYLMILAFFIVK*
>PRND_ttr Tursiops truncatus dolphin 1 trace ti|1435196145
MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKALPSTSQVTEAHTAEIRPGA
>PRND_ornana Ornithorhynchus anatinus (platypus) 42% to opposum 187 aa 4 cys in register
FIRQGRKLDINFGAEGNRYYEANYWQLPDGIHYNGCSEANVTKEKFVTSCINATQAVNQ
MMTVRRRRRSGGARWLLVFLVLLSGDLSSLQARGPRPRNKAGRKPPPSNAGPDSPAPRPPAGARGTFIRRGGRLSVDFGPEGNGYYQANYPLLPDAIVYPDCPTANGTREAFFGDCVNATHEANRGELTAGGNASDVHVRVLLRLVEELCALRDCGPALPTGPAPRPGPPGPPAALALLTLVLLGAQ*
EELSREKQDNSLYQRVLWQLIRELCSNKQCDFWLERGAGLRVTLDQPMMLCLLVFIWFIVK*          
 
>PRND_chrPic Chrysemys picta (painted_turtle)
>PRND_pcw Physeter catodon sperm whale middle fragment
MGRTRMVTCWMAMLLLVLCSNITLCRRGSSSKKASQNKSPPPVNKPSPPTKKEPVKIPGTLCYTGQLLDIKLEPEEAKYYTDNFKKFPDCIYYPRCFQSLEPNATKDTLVSECFNVTVSLTENKLDLPEGKNATSVYSRVMWQVISHLCAMEFCCQPCSLALSIHGSFGWLAMLCLGSFISLTMQ*
KALPSTSQVTEAHTAEIVPGAFIKQGRKLDIDFGAEGNRYYEANYWQFPDGIHYNGCSEA
SVTKEKFVTSCINATQEVNQEELSLEKPDNKLYQRVLWRLIRELCSI
>PRND_anocar Anolis carolinensis (lizard) weak but real! scaffold_1221:78,884-117,121 syntenic, oriented like PRNP but no larger
 
MMQRPLVVAILLTALWSEVCLCRRVSGSANRRNKKTSTTTSAPKLQSSTTATTFQGNLCRGGQMIDNMDLEPNDKVYYKANLKIFPDGLYYPNCSLLLQPNTTKEELVGECVNFTIASNKLNLSKGKDLSNTKERVMWVLIHHLCANESCGQPCPLLQNSGNLHYIGQVLTVFVGLIGCSFLSAK*
>PRND_ssc Sus scrofa pig full length ti|470951185  
MRKHLGGRRWAIVCILLFSQLSEVKARGIKHRIKWNRKALPSTSQVTEAHTAEMRPGAFI
KQGRKLDIDFGAEGNRYYEANYWRFPDGIHYNGCSEVNVTKEKFVTSCINTTQAANQEE
SHEKPDNKLYQRVLWRLIRELCSIKHCDFWLERGAGLRVTMDQPMMLCLLVFIwfivk*   
 
>PRND_sar Sorex araneus shrew Laurasiatheria; Insectivora 7.23M tr
MRKHLGWCLAIACVLLLCQVPAAQARGIKHRIKWGRKAPPSTPQVTEARVAEIRPGAFI
RQGRKLNLNLGGEDKRYYDAYYWQFPDGIHYNGCSSANVTREKFISGCINATRAANQ
EELSREKHDKLYQRVLWRLVRELCSLKRCDFWSERGAGLQVTVDQLMMFCLLAFTWFIMK*  
 
>PRND_eeu Erinaceus europaeus 10,952,642 seq complete
MRKHLGGWWLAIVCVLFFSQLSAVKARGIKHRFKWNRKALPSTNHVTEAQVSEIRPGAFI
RQGTKLDIDLGAEANRYYEANYWQFPDGIHYNGCSEVNVTKAKFIASCINATHSANQ
EELSREKHDKLYQRVLWRLVRELCSLKRCDFWSERGAGLQVTVDQLMMFCLLAFTWFIMK*
   
   
>PRND_ban Boreoeuthere ancestralis
  >PRND_pytMol Python molurus (python) AEQU010389504
MRKHLGAWWLAIVCILLFSHLSTVKARGIKHRIKWNRKALPSTAQVTEAHVAEIRPGAFI
  MWKNLLVVVLLAVLCSNVGLCRRRSGPTRKWPEKTVSKSSTKSSTTLGNLCYGSEMIDNMILEANDTTFYKDNAKEFPNGLFYPNCSLPLQPKVSRETRTEECVDFIIASSNLTLPNGKNASDPSKRVMWLVINHLCASETCSLPCPGSSNVSSAHYFLPILMTALVGYSILATR
RQGRKLDIDFGAEGNRYYEANYWQFPDGIHYNGCSEANVTKEMFVTSCINATQAANQEEF
SREKQDNKLHQRVLWRLIRELCSIKHCDFWLERGAGLRVTLDQPVMLCLLVFIWFMVK*
 
>PRND_dno Dasypus novemcinctus pseudo frag
ANYWQLPDGILYDGCAEANVTKEALVAGCVNGHTAANQAELAHERQDTLHGRVLGRLIRELCALKRCKFWPDR
 
>PRND_dno Dasypus novemcinctus
MRKHLGGWRLAIVCVLLSGHLSMVKARGIKHRIKWNRKAAPGAAQVTEARVAEQRPGAFV
RQGRRLDIDFGAEGNRYYEANYWQLPDGILYDGCAEANVTKEALVAGCVNATQLANQAEL
AHEGQDTLHRRVLGRLIRELCALKRCKFWPDRAAGPRLVRGAPVFGGLLLLIWLLVR*
 
>PRND_cho Choloepus hoffmanni sloth single trace old dasypus pseudogene, ti|563245674
MRKHLGGWWLAAVFVLLVCHLSVAKARGIKHRIKWNRKALPSAAQVTEARIAESRPGAFI
KQGRKLDIDFGAEGNKYYEANYWQFPDGIHYDGCSEANVTKEVFVTGCINATQAANQAEF
SREKHDKLHQRVLWRLIRELCSVKHCDFWLERGGGLRLTVDQPVVSACWFHLAYRE*
 
>PRND_laf Loxodonta africana African elephant Afrotheria 176 aa revised/corrected
MRKHLGAWWLAIAFVLLLSHLSMVTARGIKHRIKWNRKALPNTGHVTAAQVTETRPGAFI
RHGRKLDIDFGAEGNRYYEANYWQFPDGIHYDGCSEANVTKEMFVTSCINTTQAANQEEF
SRKQDNKVYQRILWRLIRELCSVKHCDFWLDRGGGLRVSLDQPVMLCLLVFIWFMVK*  
 
>PRND_ema Elephas maximus Asiatic elephant Afrotheria fragment
KALPNTGHVTAAQVTETRPGAFIRHGRKLDIDFGAEGNRYYEANYWQFPDGIHYDGCSEA
NVTKEMFVTSCINTTQAANQEEFSREKQDNKVYQRILWRLIRELCSV
 
>PRND_pca Procavia capensis (cape rock hyrax) Afrotheria fragment AY130772 ti|1293358170
KPVTNPAHMTAAQVSDRRLGTFIRHGRKLDIDFGAEGNRYYEANYWLFPDGIHYDGCSDT
NVTKELFVTNCINTTQAVNQEEFSREKQDNKLYQRILWRLIRELCSllglDFWPERVGGLffSLDQPVMLCLLVFIWFMLK*
 
>PRND_ete Echinops telfairi Madagascar lesser tenrec Afrotheria 10,323,158 seq
MRKHLGAGWLALACVLLFGHLSVVPARGIKHRIKWNRKTLPSTAHVTEARVSVTRPGAFV
RHGQKLDVDLGADGNRYYEAHYWQFPDGIHYDGCSDANVTREMLVTRCINATQAANQAEF
SAPPRDQQDSRLHQRVLWRLIRELCSAKRCDFWLEGAGASRAGLDQPPVLLGLLVLLGLTVK*
 
>PRND_tma Trichechus manatus (Caribbean manatee) Afrotheria fragment
KPLPNTPHVTAAQVSDARPGAFIRHGRKLDIDFGAEGNRYYEANYWQFPDGIHFDGCSEA
NVTKEMFVTSCINTTQAANQEEFSREKQDNKLYQRILWRLIRELCSV
 
>PRND_mdo Monodelphis domestica doppel genomic revised +rassf2 -prnd -prnp
MRRHLGICWIAIFFALLFSDLSLVKAKTTRQRNKSNRKGLQTNRTNPTTVQPSEKLQGTF
IRNGRKLVIDFGEEGNSYYATHYSLFPDEIHYAGCAESNVTKEVFISNCVNATRVINKLE
PLEEQNISDIYSRILEQLIKELCALNYCEFRTGKGTGLRLSLDQYVMVYLVILTCLIVK*
 
>PRND_meu Macropus eugenii wallaby
MRRHLGTWWTAIFFALLFSDLSLVKAKGTRQRNKSNRKSLQTNRVNPTTAQPSEILQGAF
IRQGRKLSIDFGEEGNSYYETHYQLFPDEIHYVGCTESNVTKDIFISNCMNATHAVNNLE
TLEEKNASDIHSRVLEQLIKELCALKYCELETETGAGLKLSLDQSVMVYLVILTCLIVK*
 
>PRND_oan Ornithorhynchus anatinus platypus 42% to opposum 187 aa 4 cys in register
MMTVRRRRRSGGARWLLVFLVLLSGDLSSLQARGPRPRNKAGRKPPPSNAGPDSPAPRPPAGARGTFIRRGGRLSVDFGPEGNGYY
QANYPLLPDAIVYPDCPTANGTREAFFGDCVNATHEANRGELTAGGNASDVHVRVLLRLVEELCALRDCGPALPTGPAPRPGPPGPPAALALLTLVLLGAQ*
 
>PRND_aca Anolis carolinensis weak but real! scaffold_1221:78,884-117,121 syntenic, oriented like PRNP but no larger
MMQRPLVVAILLTALWSEVCLCRRVSGSANRRNKKTSTTTSAPKLQSSTTATTFQGNLCRGGQMI
DNMDLEPNDKVYYKANLKIFPDGLYYPNCSLLLQPNTTKEELVGECVNFTIASNKLNLSK
GKDLSNTKERVMWVLIHHLCANESCGQPCPLLQNSGNLHYIGQVLTVFVGLIGCSFLSAK*
 
>PRND_xtr Xenopus tropicalis frog 182 aa single exon 2 cDNAs odd unbalanced cysteines syntenic turtle-prnp like, no laevis
MGRQNLFSCLILLLLILYCSLSSPRRAASSKKISKTTDLSRGAKRRPKVTNSPALGDLSFRGRALNVNFNLTEESELYTANLYSFPDGLYYPR
PAHLSGAGGTDEFISGCLNTTIERNKVWISQLEDDEEGDIYMSVATQVLQFLCMENYVKPTNGAVTCTGGLWVFIGVMHFFFLFRKGD*
</pre>
<pre>
>PRND_aca Anolis carolinensis dna sequence
atgatgcagagacctctggtagtagccatccttttgacagccctatggagcgaggtctgtctctgtcggcgagtgagcgg
atctgcaaataggcggaataagaagacttccaccaccacaagtgctcccaaacttcaaagctcaaccacagccacaacct
tccaaggaaatctttgtcgtggtggtcaaatgattgacaatatggacctcgagccaaatgacaaagtctattacaaggca
aacctgaagattttcccagatggactttattatcccaactgttccttgcttctgcagcccaacacgaccaaagaagagct
cgttggtgaatgcgtcaatttcaccattgcatcaaataagttgaacctatctaaaggcaaggatttgagcaacacaaagg
agagggtgatgtgggtcttgattcatcacttgtgtgcaaatgagtcgtgcggtcagccttgccctttgctccaaaactct
ggaaatctccactatattggccaagtactcactgtatttgttggcctaattggttgctcttttctttctgcaaaataa
</pre>
 
<h3>Dating doppel: missing from bird and fish genomes -- but present in marsupial, lizard and frog</h3>
 
The prion and doppel genes represent a local tandem duplication that has descended intact in most lineages with the two genes remaining adjacent and unpseudogenized (though both have spawned additional retroposed pseudogenes). When did this gene duplication take place, did it correlate with or facilitate an evolutionary advancement, and how have the (largely unknown) normal functions of the two genes since diverged? Retention of the second copy is somewhat puzzling in view of viability of PRNP knockouts, indeed [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15161660">double knockouts].
 
The weak homology between prion and doppel, below 30% identity even for the conserved core, suggests either a quite ancient duplication (lamprey era?) followed by average divergence, or alternatively, a fairly recent duplication (tetrapod era?) followed by rapid evolution on the doppel side as it acquired a auxillary function (neofunctionalized). These possibilities can be distinguished by looking at earlier diverging species that put a date on the duplication event.
 
If the duplication is old, then doppel should be found in various draft vertebrate genomes now available -- 34 mammals (see [[Genome completion status]]), chicken, lizard, frog, zebrafish, tetraodon, fugu, medaka, and stickleback. If gene order and orientation (synteny) are conserved, doppel will lie between PRNP and RASSF2, allowing highly diverged forms to be recognized that might give unconvincing blast matches. Of course synteny can be supplemented by conservation of internal signatures such as signal peptide, post-translationally modified arginine, disulfides, glycosylation sites, alpha helices, short beta sheet (YMLG in human), and GPI attachment. Repeat structure is trickier to use because it has been lost in all doppels and shifts from biphasic hexapeptide in frog, turtles, birds, and lizards to decapeptide (platypus), nonapeptide (marsupial), to octapeptide (placentals).
 
The brushtail opossum (Trichosurus vulpecular) prion gene sequence was determined in 1995. It conserves  structural elements overall but presents various anomalies such as nonapeptide repeats. Its sequence can be used as query at the [http://genome.cse.ucsc.edu/cgi-bin/hgGateway?hgsid=99826923&clade=vertebrate&org=Opossum&db=0 UCSC genome browser] to find a complete second marsupial PRNP sequence from Monodelphis domestica. The two proteins have  86% sequence identity (not including repeat region), not necessarily indicating faster divergence since marsupials have had longer to diverge than placental mammals. The two 'opossums' here are not closely related, Didelphimorphia vs Diprotodontia. The second marsupial genome (Macropus eugenii) has been released unassembled to NCBI trace archives; full length PRNP and PRND sequences are readily covered there by trace blastn.
 
Monodelphis domestica PRND is located next to PRNP in the same orientation in a gapless region of the assembly. Within placental mammals, doppel homology is about 85% identity but this drops off to 46% relative to marsupial, indicating a relative fast-evolving protein in this lineage (but not yet a pseudogene). Indeed, with nearly PRNP gene sequences available in nearly a hundred species of placentals and the mammalian phylogenetic tree topology [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17322288,17975064 finally determined], clade-specific rate variations could be pursued in unusual detail, with a possible correlation with rates of doppel evolution.
 
Monotreme represents a still earlier divergence: PRNP  and PRND can be recovered from the newly released assembly of the platypus genome, Ornithorhynchus anatinus. This species, which diverged after birds but before the Metatherian/Eutherian split, has a decapeptide x 4 repeat (rather than a bird- or turtle-like hexapeptide. However its sequence, PQGGGASWGH, is unusual for its glutamine in second position and terminal histidine (reverse of usual mammal residues). In other respects it is conventional.
 
The chicken genome is gap-free in this area and retains mammalian gene order and orientation (PRNP+, RASSF2-, and SCL23A-). However, no dopple gene occurs in chicken in the expected position. If prion gene duplication occurred prior to chicken divergence, then doppel decayed to an unrecognizable pseudogene, translocated to an unsequenced region, or has been deleted. No evidence for a decayed pseudogene is observed using a high-sensitivity blast of reconstructed ancestral doppel. The other bird genome underway, Taeniopygia guttata (finch), also lacks PRND.
 
Very recently, a lizard genome became available, Anolis carolinensis. Using specialized methods, a full length PRND gene has be located in expected syntenic position and validated by retained internal signatures despite its very weak blast score. Similarly in the diploid frog, Xenopus tropicalis, an unmistakable frog doppel gene occurs at expected position and orientation. These results have a simple  parsimonious explanation: the PRND duplication predated amphibian divergence, followed by a lineage-specific deletion in the bird clade. Crocodile sequencing could refine the date of this event.
 
In support, lizard and frog doppel queries retrieve solely mammalian and turtle PRND genes when back-blasted against the GenBank non-redundant nucleotide division. This argues against the idea of multiple independent duplications of the prion gene in lizard and frog distinct from a later lineage-specific duplication in mammals (with birds then never having a PRND to delete).
 
Note the more familiar tetraploid laboratory frog,  Xenopus laevis, has two actively transcribed PRNP genes that differ slightly in the repeat-like region as well at a few individual amino acids. Their sequences are given below. No sign of doppel can be found in Xenopus laevis cDNA (unsurprisingly since doppel transcription is rare); no genome project is underway. There may be two doppels in this species, depending on the relative timing of PRNP duplication and the tetraploidization event and selective pressure to maintain two copies.
 
The prion gene in teleost fish has radically diverged from its mammalian counterpart especially in the repeat region but remains recognizable via various conserved anchor features, residual synteny, and weak homology. Fugu has a second PRNP gene on a different chromosome (resulting from the whole genome duplication in Teleostei) plus an apparent novel tandem duplication that resembles PRNP rather than PRND. Coelocanth genome has been proposed but not begun -- that could further refine the timing of PRND duplication. As it stands, that event occurred after teleost fish divergence but before that of amphibians, about 400 million years ago. The prion gene clearly represents the ancestral form and presumably function, ie, a doppel-like ancestor did not duplicate to a second gene that become PRNP. No counterpart of PRNP can be located in the initial release of the chondrichthyian genome, Callorhynchus milii, but that will be finished to higher coverage in a few months.
 
Doppels are evolving noticeably faster than prions but have not become pseudogenes in any species investigated to date. (Note very recent pseudogenes that have not yet acquired internal stop codons or loss of deeply invariant residues are difficult to detect.) It must be remembered that PRNP's globular region lies within the most slowly evolving quartile of mammalian genes. As a representative example, human/dog proteins have 78% identity for PRND but 87% for PRNP. A reconstructed ancestral mammal sequence for PRND shows no sign whatsoever of converging to a PRNP-like sequence, percent identity ancester-to-ancestor remains in the mid-20's. Since this uses up 100 million years of the 400 available, doppel evolved more drastically at an earlier time, perhaps soon after the duplication event.
 
To further investigate the co-evolution of PRNP and PRND, it is imperative to first collect gene sequences from a phylogenetically representative sample of species. PRNP tends to be over-sampled within Artiodactylia, indeed Bovidae. Doppel remains very poorly represented at dbEST even within much-studied mammals and enriched libraries, even in testis, a tissue where it is transcribed. The most economical explanation of the data is that doppel has a narrow function with limited and specialized expression in uncommon cell types, yet one important enough for gene retention.
 
However a respectable number of tetrapod doppel sequences have accumulated. In addition to genome projects, van Rheede and coworkers sequenced nine doppels from important early diverging clades of placental mammals. PRND from the chimpanzee genome has special interest for evaluating known human doppel polymorphisms to determine "wildtype" human. Macaque doppel can also the 2 amino acid deletion seen in human at position 122-123, showing this event predated old world monkey divergence. In fact that event can be precisely timed to the stem lying between tarsier and new world monkey divergence and shown non-homplasic using various genome projects underway:
 
<pre>
PRND_hsa  ANQGEFQ--KPDNKLHQQVLWRLVQELCS  Homo  sapiens  (human)
PRND_ptr  ANQGEFQ--KPDNKLHQQVLWRLVRELCS  Pan  troglodytes  (chimp)
PRND_ggo  ANQGEFH--KPDNKLHQQVLWRLVRELCS  Gorilla  gorilla  (gorilla)
PRND_ppy  ANQGEFQ--KPDNKLHQQVLWRLVQELCS  Pongo  pygmaeus  (orang_sumatran)
PRND_nle  ANQGEFQ--KPDNKLHQRVLWRLVRELCS  Nomascus  leucogenys  (gibbon)
PRND_mml  ENQGEFQ--KPDNKLHQRVLWRLVQELCS  Macaca  mulatta  (rhesus)
PRND_pha  ANQGEFQ--KPDNKLHQRVLWRLVQELCS  Papio  hamadryas  (baboon)
PRND_cja  ANQAEFQ--KPDNKLHQRVLWRLVQELCS  Callithrix  jacchus  (marmoset_nwm)
PRND_tsy  ANAAERPREARDDPLHQRVLGRLVRELCS  Tarsius  syrichta  (tarsier)
PRND_mmr  ANQAEFAREKQD-KLHERILWRLTRELCS  Microcebus  murinus  (mouse_lemur)
PRND_tbe  ANQAEFSKEKQDNKLYQRVLWRLIKELCS  Tupaia  belangeri  (tree_shrew)
PRND_ocu  ANQGEFSREKQDNKLHQRVLWRLIKELCS  Oryctolagus  cuniculus  (rabbit)
PRND_opr  ANQGEFSREKQ-NKLHQRVLWRLIKELCS  Ochotona  princeps  (pika)
PRND_dor  ANQAEFAREMQD-KFYQRVLWRLTKELCA  Dipodomys  ordii  (kangaroo_rat)
PRND_str  ANQAEFSREKQDNKLHQRVLWRLIKELCS  Spermophilus  tridecemlineatus  (ground_squirrel)
PRND_rno  ANQAEFSREKQDSKLHQRVLWRLIKEICS  Rattus  norvegicus  (rat)
PRND_mmu  ANQAEFSREKQDSKLHQRVLWRLIKEICS  Mus  musculus  (mouse)
PRND_cpo  ANQAEFSREKQDNKLHQRILWRLIKELCS  Cavia  porcellus    (guinea_pig)
PRND_sar  ANQEELSREKHD-KLYQRVLWRLVRELCS  Sorex  araneus  (shrew)
PRND_eeu  ANQEELSREKHD-KLYQRVLWRLVRELCS  Erinaceus  europaeus  (hedgehog)
PRND_cfa  ANQEELSREKQDNKLHQRVLWRLIRELCS  Canis  familiaris  (dog)
PRND_fca  ANQEELSREKQDDKLYQRVLWRLNR-ECS  Felis  catus  (cat)
PRND_tte  ENQEELSREKQDDKLHQRILWRLIRELCS  Tapirus  terrestris  (tapir)
PRND_eca  ANQEELSQEKQDDKLYQRILWRLISELCS  Equus  caballus  (horse)
PRND_mlu  ANQEELSQERPDNRLHRRILWRLVRELCS  Myotis  lucifugus  (microbat)
PRND_csp  VNQEELSQEKQDKLLHQRILWQLIRELCS  Cynopterus  sphinx  (bat)
PRND_oar  ANQEELSREKQDNKLYQRVLWQLIRELCS  Ovis  aries  (sheep)
PRND_chi  ANQEELSREKQDNKLYQRVLWQLIRELCS  Capra  hircus  (goat)
PRND_bta  ANQEELSREKQDNKLYQRVLWQLIRELCS  Bos  taurus  (cow)
PRND_ttr  VNQEELSREKQDNSLYQRVLWQLIRELCS  Tursiops  truncatus  (dolphin)
PRND_ssc  ANQEE-SHEKPDNKLYQRVLWRLIRELCS  Sus  scrofa  (pig)
PRND_pcw  VNQEELSLEKPDNKLYQRVLWRLIRELCS  Physeter  catodon  (whale)
PRND_ban  ANQEEFSREKQDNKLHQRVLWRLIRELCS  Boreoeuthere  ancestralis  (boreoeuthere)
PRND_dno  ANQAELAHERQD-TLHGRVLGRLIRELCA  Dasypus  novemcinctus  (armadillo)
PRND_cho  ANQAEFSREKHD-KLHQRVLWRLIRELCS  Choloepus  hoffmanni  (sloth)
PRND_pcp  VNQEEFSREKQDNKLYQRILWRLIRELCS  Procavia  capensis  (hyrax)
PRND_ete  ANQAEFSAPQQDSRLHQRVLWRLIRELCS  Echinops  telfairi  (tenrec)
PRND_ema  ANQEEFSREKQDNKVYQRILWRLIRELCS  Elephas  maximus  (elephant)
PRND_laf  ANQEEFSR-KQDNKVYQRILWRLIRELCS  Loxodonta  africana  (elephant)
PRND_tma  ANQEEFSREKQDNKLYQRILWRLIRELCS  Trichechus  manatus  (manatee)
PRND_mdo  INKLEPLEEQNISDIYSRILEQLIKELCA  Monodelphis  domestica  (opossum)
PRND_meu  VNNLETLEEKNASDIHSRVLEQLIKELCA  Macropus  eugenii  (wallaby)
PRND_oan  ANRGELTAGGNASDVHVRVLLRLVEELCA  Ornithorhynchus  anatinus  (platypus)
PRND_aca  SNKLNLSKGKDLSNTKERVMWVLIHHLCA  Anolis  carolinensis  (lizard)
PRND_xtr RNKVWISQLEDDEEGDIYMSVATQVLQFLCM  Xenopus  tropicalis  (frog)
          ** * .  * *. ::*::**:* :* .:   
</pre>
Below 45 PRND doppel sequences from land vertebrates are provided. Most are complete and reliable, but others are fragmentary and no better than the ongoing genome project from which they were extracted (initially low coverage, perhaps a single applicable trace). The phylogenetic distribution is approximately half as extensive as for PRNP. Almost all species having an available PRND would also have an available PRNP. It would be very easy to extend PRND coverage since primer design for PCR presents no issues. All sequences consist of a single coding intron. The only rare genomic event for PRND of any phylogenetic depth is the indel shown above.
 
<pre>
11 primates (Euarchonta)
7 glires (rodents and rabbits)
14 laurasiatheres
1 ancestral boreoeuthere
2 xenarthrans
5 aftrotheres
2 marsupial
1 platypus
0 bird
1 lizard
1 amphibian
</pre>
 
 
<pre>
>PRND_hsa human full length
MRKHLSWWWLATVCMLLFSHLSAVQTRGIKHRIKWNRKALPSTAQITEAQVAENRPGAFIKQGRKLDIDFGAEGNRYY
EANYWQFPDGIHYNGCSEANVTKEAFVTGCINATQAANQGEFQKPDNKLHQQVLWRLVQELCSLKHCEFWLERGAGLRVTMHQPVLLCLLALIWLTVK*
 
>PRND_ptr Pan chimpanzee full length
MRKHLSWWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSTAQITEAQVAENRPGAFIKQGRKLDIDFGAEGNRYY
EANYWQFPDGIHYNGCSEANVTKEVFVTGCIHATQAANQGEF
QKPDNKLHQQVLWRLVRELCSLKHCEFWLERGAGLRVTMHQPVLLCLLAFIWLMVK*
 
>PRND_ggo gorilla
MRKHLSWWWLATVCMLFFSHLSAVQARGIKHRIKWNRKALPSTAQITEAQVAENRPGAFIKQGRKLDIDFGAEGNRYY
EANYWQFPDGIHYNGCSEANVTKEVFVTGCINATQAANQGEF
HKPDNKLHQQVLWRLVRELCSLKHCEWLERSAGLRVTMHQPVLLCLLAFIWLMMK*
 
>PRND_ppy Pongo pygmaeus orangutan shares 2 bp deletion unique to primates.
MKNHLSWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSTAQITEAPGAENRPGALSkQGR 
QLDIDFGTEGNRYYEANYWQFPDGIHYDGCSEANVTKEVFVTGCINATQAANQGEFQ
KPDNKLHQQVLWRLVQELCSLKHCEFWLERGAGLRVTMHQPVLLCLLAFIWLMVK*
 
>PRND_nle Nomascus leucogenys gibbon
MRKHLSWWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSTAQITEAQVAENRPGGFIKQGRKLDIDFGAEGNRYY
EANYWQFPDGIHYDGCSEANVTKEVFV
TGCINATQAANQGEFQKPDNKLHQRVLWRLVRELCSLKRCEFWLERGAGLRVTMHQPVLLCLLAFIWLMVK*
 
>PRND_pha Papio hamadryas (baboon)
        WLSRLHAAPQ HLSLVVQARGIKHRIKWNRKALPSTAQITEAQVAENPPGSFIKQGRKLNIDFGAEGNRYY
EANYWQFPDGIHYDGCSEANVTKEVFVTGC
INATQAANQGEFQKPDNKLHQRVLWRLVQELCSLKRCEFWLEGGAGLRVTMHQPVLLCLPAFVWLMVK*
 
>PRND_mml Macaca mulata full length from trace archives
MRQHLSRWWLATVCMLLLSHLSVVQARGIKHRIKWNRKALPSTAQITEAQVAENRPGAFIKQGR
KLNIDFGAEGNRYYEANYWQFPDGIHYDGCSEANVTKEVFVTGCINATQAENQGEFQK
PDNKLHQRVLWRLVQELCSLKRCEFWLERGAGLRVTMHQPVLLCLPAFVWLMV*
 
>PRND_cja Callithrix jacchus 1st new world monkey 89% 
MRKHLSGWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSAAQITEAQVAENRPGTFIKQGRKLDINFGAEGNRYY
EANYWQLPDGIHYDGCSETNVTKEVFVTGCINATQAANQAEFQKPDNKLHQRVLWRLVQELCSLKRCEFWLERGAGFRVATHQPLLLCLLAFIWLMAK*
 
>PRND_tsy Tarsius syrichta tarsier
MRKPLGGWRLAVVCVLLLGLLSAARARGIKHRFKWNRKASPSAARVTEARVAESRPGAFIRRGRKLDIDFGAEGNKYY
EANYWQFPDGIHYDGCSKANVTKELLVAGCINATHAANAAERPREARDDPLHQRVLGRLVRELCSAKHCDFWPERAAAPGTARARPGALLLVSRL
 
>PRND_mmr Microcebus murinus
GNRYYEANYWQFPDGIHYDGCSDANVTKEVFVASCINATVAANQAEFAREKQDKLHERILWRLTRELCSVKRCEFWLERGAGLRVAEDCPTILSLLLLLWLLLR*
 
>PRND_tbe Tupaia belangeri tree shrew 6.7 m tr frag
RALPSTAHITEARVAENRPGAFIRQGRKLDIDFGVEGNRYYEANYWQFPDGIHYDGCSEVNVTKEMFITSCINATQA
ANQAEFSKEKQDNKLYQRVLWRLIKELCSIKHCDFWLERGAGLRVTMHLPVMLCLLVFVWFVVK*
 
>PRND_mmu Mus musculus mouse full length
MKNRLGTWWVAILCMLLASHLSTVKARGIKHRFKWNRKVLPSSGGQITEARVAENRPGAF
IKQGRKLDIDFGAEGNRYYAANYWQFPDGIYYEGCSEANVTKEMLVTSCVNATQAANQAE
FSREKQDSKLHQRVLWRLIKEICSAKHCDFWLERGAALRVAVDQPAMVCLLGFVWFIVK*
   
   
>PRND_rno Rattus norvegicus rat full length
>PRND_xenTro Xenopus tropicalis (frog) 182 aa single exon 2 cDNAs odd unbalanced cysteines syntenic turtle-prnp like, no laevis
MKNRVGTWGLAILCLLLASHLSTVKARGIKHRFKWNRKVLPSSGQITEAQV
  MGRQNLFSCLILLLLILYCSLSSPRRAASSKKISKTTDLSRGAKRRPKVTNSPALGDLSFRGRALNVNFNLTEESELYTANLYSFPDGLYYPRPAHLSGAGGTDEFISGCLNTTIERNKVWISQLEDDEEGDIYMSVATQVLQFLCMENYVKPTNGAVTCTGGLWVFIGVMHFFFLFRKGD*
AENRPGAFIKQGRKLDIDFGAEGNKYYAANYWQFPDGIYYEGCSEANVTKEVLVTRCVNA
TQAANQAEFSREKQDSKLHQRVLWRLIKEICSTKHCDFWLERGAALRITVDQQAMVCLLGFIWFIVK*
 
>PRND_cpo Cavia porcellus (guinea pig) fragment AY130773 N-extended at traces 7,499,469 seq
MKTSLCVWALVCVLLQCHFSSVAARGIKHRIRWGRKPTPSPSQVTEARVAMTRPGAFIKEGHKLNIDFGAEGNRYYETNYWQFPDGIHYNGCSDT
NVTKEVLVTSCINATQAANQAEFSREKQDNKLHQRILWRLIKELCSA
 
>PRND_dor Dipodomys ordii pseudogene
ITEARYRENAQGPSSIKP--QADIDF--ERAQ*YEA*YWQFADGINYEGCSRRHVTKQMF
VSRCINVTQAANQAEFAREMQD-KFYQRVLWRLTKELCAVKQCDFWLERGEGCPVAIVNR
PAMLGLLLCMWFIL
 
>PRND_str Spermophilus tridecemlineatus ground squirrel complete tr
MKKHLGTWGLAVVCVLLSTHLSAIKARGIKHRIKWNRKSVPSTVQITEAQVAQNPPGAF
IKQGRKLHIDFGAEGNKYYEANYWQFPDGIYYDGCSEANVTKEVFIAKCINATQAANQAE
FSREKQDNKLHQRVLWRLIKELCSVKHCDFWLEGGAGFQLSVDQPVMLCLLVFIWLMVK*
 
>PRND_ocu Oryctolagus cuniculus rabbit revised complete from traces 8,968,713 sequences 75%
MRKHLGAWGLAIVCVLLFSHLPPAKARGIKHRIKWNRKALPSTAQITEAHVAENRPGTFI
RQGRKLNIDFGPEGNKYYEANYWQFPDGVHYDGCSEGNVTKEAFVAKCVNATQAANQGE
FSREKQDNKLHQRVLWRLIKELCSIKHCDFWLERGAGVQVGGEQPLVLGLLLCTWLLVK*
 
>PRND_opr Ochotona princeps pika complete
MRKHLGGWGLAIVCVLLFSLLPTVKARGIKHRIKWNRKALPSTAQITEARVAENRPGTFIRQGQKLSIDFGPEGNKYY
EANYWQFPDGIHYDGCSEGNVTKEVFVAKCINATQAANQGEFSREKQNKLHQRVLWRLIKELCSIKHCDFWLERGAGFPVTVGQPMVVLCLLIFTWVLVK*
 
>PRND_cfa Canis familiaris dog full length
MRKHLGGCWLAIVCVLLLSQLSAVEARGIKHRIKWNRKALPGTSQVTEARSAEIRPGAFI
RQGRKLDIDLGPEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTGCINATQVANQEEL
SREKQDNKLHQRVLWRLIRELCSVKRCDFWLERGAGPRVAGAQPVLLCLLAFIWFIVK*
 
>PRND_fca Felis catus cat improved fragment 8,248,053 traces now 9.2
MRKHLGGCWLAIVCVLLFSQLSAVKARGIKHRIKWNRKTLPSISQVTEAHTAEIRPGAFIRQGRKLDIDLG
AEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTSCINATQVANQEELSREKQDhKLYQRVLWRLNREALLWSAHGNFGRERG
 
>PRND_eca Equus caballus perissodactyl
MRKHLGGCCLAIVCVLLFSQLPVVLSRGTKHRIKWNRKALPSTAKVTEARVEEIRPGAF
IRQGRKLNINFGAEGNRYYEANYWQFPDEIHYNGCSEANVTKEKFVISCINATQEANQEE
LSQEKQDDKLYQRILWRLISELCSVKHCDFGLESGTGLRVTMDQPVLLCLLVFIWFIVK*
 
>PRND_tte Tapirus terrestris (Brazilian tapir) perissodactyl fragment
KALPSTSKVTEAHTAEIRPGAFIRQGRKLNIDFGAEGNRYYEANYWQFPDEIHYNGCSEA
NVTKEKFVISCINATQAENQEELSREKQDDKLHQRILWRLIRELCSV
 
>PRND_mlu Myotis lucifugus traces ti|983665423 complete
MRKQLGGCCLAIVCVLLFSQLAAVQARGIKHRIKWNRKGAAPPSSSQVTEAQRVEMQLRP
GAFIKHGRKLDIDFGAEANRYYEANYWQFPDEIHYNGCSSEANVTREKFVSGCINATQAA
NQEELSQERPDNRLHRRILWRLVRELCSVKHCDFWLENGAGLWVTVHRPVMPCLLVSIWFIVK*
 
>PRND_pva Pteropus vampyrus frameshifty frag
MRRQLGGCWLAIVCVLLFSQLSTVKARGIKHRTKWNR PCDRVS VTESQ GAFIKQGRK
 
>PRND_csp Cynopterus sphinx bat  Laurasiatheria; Chiroptera fragment
KTLPSPSSHVTESQTAEMRPGAFVKQGRKLNIDFGDEGNRYYEAHYWEFPDGIYYDACSKANVTKEK
FVTSCINATQAVNQEELSQEKQDKLLHQRILWQLIRELCSV
 
>PRND_bta Bos taurus cow full length
MRKHLGGCWLAIVCILLFSQLCSVKARGIKHRIKWNRKVLPSTSQVTEARTAEIRPGAFI
KQGRKLDIDFGVEGNRYYEANYWQFPDGIHYNGCSKANVTKEKFITSCINATQAANQEEL
SREKQDNKLYQRVLWQLIRELCSTKHCDFWLERGAGLRVTLDQPMMLCLLVFIWFIVK*
 
>PRND_oar Ovis aries sheep full length
MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKVLPSTSQVTEAHTAEIRPGAFI
KQGRKLDINFGVEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTSCINATQVANQEEL
SREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLQVTLDQPMMLCLLVFIWFIVK*
 
>PRND_chi Capra hircus (goat)
MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKVLPSTSQVTEAHTAEIRPGAFIKQGRKLDINFGV
EGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTSCINATQVANQEELSREKQDNKLYQRVLWQLIREL
CSIKHCDFWLERGAGLQVTLDQPMMLCLLVFIWFIVK*
 
>PRND_ama Antidorcas marsupialis (springbok) Bovidae; Antilopinae
MRKHLGGCWLAIACILLFSQLSSVKARGIKHRIKWNRKVLPSTS
QVTEAHTAEIRPGAFIKQGRKLDIDFGVEGNRYYEANYWQFPDGIHYNGCSEANVTKE
KFVTSCINATQVANQEELSREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLRVT
LDQPMMLCLLVFIWFIVK*
 
>PRND_ttr Tursiops truncatus dolphin 1 trace ti|1435196145
MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKALPSTSQVTEAHTAEIRPGA
FIRQGRKLDINFGAEGNRYYEANYWQLPDGIHYNGCSEANVTKEKFVTSCINATQAVNQ
EELSREKQDNSLYQRVLWQLIRELCSNKQCDFWLERGAGLRVTLDQPMMLCLLVFIWFIVK*         
 
>PRND_pcw Physeter catodon sperm whale middle fragment
KALPSTSQVTEAHTAEIVPGAFIKQGRKLDIDFGAEGNRYYEANYWQFPDGIHYNGCSEA
SVTKEKFVTSCINATQEVNQEELSLEKPDNKLYQRVLWRLIRELCSI
 
>PRND_ssc Sus scrofa pig full length ti|470951185
MRKHLGGRRWAIVCILLFSQLSEVKARGIKHRIKWNRKALPSTSQVTEAHTAEMRPGAFI
KQGRKLDIDFGAEGNRYYEANYWRFPDGIHYNGCSEVNVTKEKFVTSCINTTQAANQEE
SHEKPDNKLYQRVLWRLIRELCSIKHCDFWLERGAGLRVTMDQPMMLCLLVFIwfivk* 
 
>PRND_sar Sorex araneus shrew Laurasiatheria; Insectivora  7.23M tr
MRKHLGWCLAIACVLLLCQVPAAQARGIKHRIKWGRKAPPSTPQVTEARVAEIRPGAFI
RQGRKLNLNLGGEDKRYYDAYYWQFPDGIHYNGCSSANVTREKFISGCINATRAANQ
EELSREKHDKLYQRVLWRLVRELCSLKRCDFWSERGAGLQVTVDQLMMFCLLAFTWFIMK*
 
>PRND_eeu Erinaceus europaeus 10,952,642 seq complete
MRKHLGGWWLAIVCVLFFSQLSAVKARGIKHRFKWNRKALPSTNHVTEAQVSEIRPGAFI
RQGTKLDIDLGAEANRYYEANYWQFPDGIHYNGCSEVNVTKAKFIASCINATHSANQ
EELSREKHDKLYQRVLWRLVRELCSLKRCDFWSERGAGLQVTVDQLMMFCLLAFTWFIMK*
   
   
>PRND_ban Boreoeuthere ancestralis
>PRND_anaCar Anolis carolinensis dna query sequence
MRKHLGAWWLAIVCILLFSHLSTVKARGIKHRIKWNRKALPSTAQVTEAHVAEIRPGAFI
atgatgcagagacctctggtagtagccatccttttgacagccctatggagcgaggtctgtctctgtcggcgagtgagcgg
RQGRKLDIDFGAEGNRYYEANYWQFPDGIHYNGCSEANVTKEMFVTSCINATQAANQEEF
atctgcaaataggcggaataagaagacttccaccaccacaagtgctcccaaacttcaaagctcaaccacagccacaacct
SREKQDNKLHQRVLWRLIRELCSIKHCDFWLERGAGLRVTLDQPVMLCLLVFIWFMVK*
tccaaggaaatctttgtcgtggtggtcaaatgattgacaatatggacctcgagccaaatgacaaagtctattacaaggca
 
aacctgaagattttcccagatggactttattatcccaactgttccttgcttctgcagcccaacacgaccaaagaagagct
>PRND_dno Dasypus novemcinctus pseudo frag
cgttggtgaatgcgtcaatttcaccattgcatcaaataagttgaacctatctaaaggcaaggatttgagcaacacaaagg
ANYWQLPDGILYDGCAEANVTKEALVAGCVNGHTAANQAELAHERQDTLHGRVLGRLIRELCALKRCKFWPDR
agagggtgatgtgggtcttgattcatcacttgtgtgcaaatgagtcgtgcggtcagccttgccctttgctccaaaactct
 
ggaaatctccactatattggccaagtactcactgtatttgttggcctaattggttgctcttttctttctgcaaaataa
>PRND_dno Dasypus novemcinctus
                                                      *                    *    *  *          **      ***  *  *        *      * * *  *                        **                                      
MRKHLGGWRLAIVCVLLSGHLSMVKARGIKHRIKWNRKAAPGAAQVTEARVAEQRPGAFV
PRND_homSap    -MRKHLSWWWLATVCMLLFSHLSAVQTRGIKHRIKWNRKALPSTA-QITEA-QVAENRPGAFIKQGRKLD-IDFGAEGNRYYEANYWQFPDGIHYNGCS---EANVTKEAFVTGCINATQAANQGEF--QKPDNKLHQQVLWRLVQELCSLKHCEFWLERGAGLRVTMHQPVL-LCLLALIWLTVK---
RQGRRLDIDFGAEGNRYYEANYWQLPDGILYDGCAEANVTKEALVAGCVNATQLANQAEL
PRND_ptanTro  -MRKHLSWWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSTA-QITEA-QVAENRPGAFIKQGRKLD-IDFGAEGNRYYEANYWQFPDGIHYNGCS---EANVTKEVFVTGCIHATQAANQGEF--QKPDNKLHQQVLWRLVRELCSLKHCEFWLERGAGLRVTMHQPVL-LCLLAFIWLMVK---
AHEGQDTLHRRVLGRLIRELCALKRCKFWPDRAAGPRLVRGAPVFGGLLLLIWLLVR*
PRND_gorGor    -MRKHLSWWWLATVCMLFFSHLSAVQARGIKHRIKWNRKALPSTA-QITEA-QVAENRPGAFIKQGRKLD-IDFGAEGNRYYEANYWQFPDGIHYNGCS---EANVTKEVFVTGCINATQAANQGEF--HKPDNKLHQQVLWRLVRELCSLKHCE-WLERSAGLRVTMHQPVL-LCLLAFIWLMMK---
 
PRND_ponPyg    -MKNHLS-WWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSTA-QITEA-PGAENRPGALSKQGRQLD-IDFGTEGNRYYEANYWQFPDGIHYDGCS---EANVTKEVFVTGCINATQAANQGEF--QKPDNKLHQQVLWRLVQELCSLKHCEFWLERGAGLRVTMHQPVL-LCLLAFIWLMVK---
>PRND_cho Choloepus hoffmanni sloth single trace old dasypus pseudogene, ti|563245674
  PRND_nomLeu    -MRKHLSWWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSTA-QITEA-QVAENRPGGFIKQGRKLD-IDFGAEGNRYYEANYWQFPDGIHYDGCS---EANVTKEVFVTGCINATQAANQGEF--QKPDNKLHQRVLWRLVRELCSLKRCEFWLERGAGLRVTMHQPVL-LCLLAFIWLMVK---
MRKHLGGWWLAAVFVLLVCHLSVAKARGIKHRIKWNRKALPSAAQVTEARIAESRPGAFI
PRND_papHam    -MRKHLSWWWLATVCMLLFSHLSAVQTRGIKHRIKWNRKALPSTA-QITEA-QVAENRPGAFIKQGRKLD-IDFGAEGNRYYEANYWQFPDGIHYNGCS---EANVTKEAFVTGCINATQAANQGEF--QKPDNKLHQQVLWRLVQELCSLKHCEFWLERGAGLRVTMHQPVL-LCLLALIWLTVK---
KQGRKLDIDFGAEGNKYYEANYWQFPDGIHYDGCSEANVTKEVFVTGCINATQAANQAEF
PRND_macMul    -MRQHLSRWWLATVCMLLLSHLSVVQARGIKHRIKWNRKALPSTA-QITEA-QVAENRPGAFIKQGRKLN-IDFGAEGNRYYEANYWQFPDGIHYDGCS---EANVTKEVFVTGCINATQAENQGEF--QKPDNKLHQRVLWRLVQELCSLKRCEFWLERGAGLRVTMHQPVL-LCLPAFVWLMV----
SREKHDKLHQRVLWRLIRELCSVKHCDFWLERGGGLRLTVDQPVVSACWFHLAYRE*
PRND_calJac    -MRKHLSGWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSAA-QITEA-QVAENRPGTFIKQGRKLD-INFGAEGNRYYEANYWQLPDGIHYDGCS---ETNVTKEVFVTGCINATQAANQAEF--QKPDNKLHQRVLWRLVQELCSLKRCEFWLERGAGFRVATHQPLL-LCLLAFIWLMAK---
 
PRND_tarSyr    -MRKPLGGWRLAVVCVLLLGLLSAARARGIKHRFKWNRKASPSAA-RVTEA-RVAESRPGAFIRRGRKLD-IDFGAEGNKYYEANYWQFPDGIHYDGCS---KANVTKELLVAGCINATHAANAAERPREARDDPLHQRVLGRLVRELCSAKHCDFWPERAAAPGTARARP---GALLLVSRL------
>PRND_laf Loxodonta africana African elephant Afrotheria 176 aa revised/corrected
PRND_micMur    -MRKHLGGWRPAIVFILLFSHLAVVKARGIKHRIKWNRKPLPSTV-HITEA-LVAENRPGAFIKQGRKLD-VDFGEEGNRYYEANYWQFPDGIHYDGCS---DANVTKEVFVASCINATVAANQAEFAREKQD-KLHERILWRLTRELCSVKRCEFWLERGAGLRVAEDCPTI-LSLLLLLWLLLR---
MRKHLGAWWLAIAFVLLLSHLSMVTARGIKHRIKWNRKALPNTGHVTAAQVTETRPGAFI
PRND_tupBel    --------------------------------------RALPSTA-HITEA-RVAENRPGAFIRQGRKLD-IDFGVEGNRYYEANYWQFPDGIHYDGCS---EVNVTKEMFITSCINATQAANQAEFSKEKQDNKLYQRVLWRLIKELCSIKHCDFWLERGAGLRVTMHLPVM-LCLLVFVWFVVK---
RHGRKLDIDFGAEGNRYYEANYWQFPDGIHYDGCSEANVTKEMFVTSCINTTQAANQEEF
PRND_musMus    -MKNRLGTWWVAILCMLLASHLSTVKARGIKHRFKWNRKVLPSSGGQITEA-RVAENRPGAFIKQGRKLD-IDFGAEGNRYYAANYWQFPDGIYYEGCS---EANVTKEMLVTSCVNATQAANQAEFSREKQDSKLHQRVLWRLIKEICSAKHCDFWLERGAALRVAVDQPAM-VCLLGFVWFIVK---
SRKQDNKVYQRILWRLIRELCSVKHCDFWLDRGGGLRVSLDQPVMLCLLVFIWFMVK*  
PRND_ratNor    -MKNRVGTWGLAILCLLLASHLSTVKARGIKHRFKWNRKVLPSSG-QITEA-QVAENRPGAFIKQGRKLD-IDFGAEGNKYYAANYWQFPDGIYYEGCS---EANVTKEVLVTRCVNATQAANQAEFSREKQDSKLHQRVLWRLIKEICSTKHCDFWLERGAALRITVDQQAM-VCLLGFIWFIVK---
 
PRND_cavPor    -MKTSLCVW--ALVCVLLQCHFSSVAARGIKHRIRWGRKPTPSPS-QVTEA-RVAMTRPGAFIKEGHKLN-IDFGAEGNRYYETNYWQFPDGIHYNGCS---DTNVTKEVLVTSCINATQAANQAEFSREKQDNKLHQRILWRLIKELCSA--------------------------------------
>PRND_ema Elephas maximus Asiatic elephant Afrotheria fragment
PRND_speTri    -MKKHLGTWGLAVVCVLLSTHLSAIKARGIKHRIKWNRKSVPSTV-QITEA-QVAQNPPGAFIKQGRKLH-IDFGAEGNKYYEANYWQFPDGIYYDGCS---EANVTKEVFIAKCINATQAANQAEFSREKQDNKLHQRVLWRLIKELCSVKHCDFWLEGGAGFQLSVDQPVM-LCLLVFIWLMVK---
KALPNTGHVTAAQVTETRPGAFIRHGRKLDIDFGAEGNRYYEANYWQFPDGIHYDGCSEA
PRND_oryCun    -MRKHLGAWGLAIVCVLLFSHLPPAKARGIKHRIKWNRKALPSTA-QITEA-HVAENRPGTFIRQGRKLN-IDFGPEGNKYYEANYWQFPDGVHYDGCS---EGNVTKEAFVAKCVNATQAANQGEFSREKQDNKLHQRVLWRLIKELCSIKHCDFWLERGAGVQVGGEQPLV-LGLLLCTWLLVK---
NVTKEMFVTSCINTTQAANQEEFSREKQDNKVYQRILWRLIRELCSV
PRND_ochPri    -MRKHLGGWGLAIVCVLLFSLLPTVKARGIKHRIKWNRKALPSTA-QITEA-RVAENRPGTFIRQGQKLS-IDFGPEGNKYYEANYWQFPDGIHYDGCS---EGNVTKEVFVAKCINATQAANQGEFSREKQ-NKLHQRVLWRLIKELCSIKHCDFWLERGAGFPVTVGQPMVVLCLLIFTWVLVK---
 
PRND_canfam    -MRKHLGGCWLAIVCVLLLSQLSAVEARGIKHRIKWNRKALPGTS-QVTEA-RSAEIRPGAFIRQGRKLD-IDLGPEGNRYYEANYWQFPDGIHYNGCS---EANVTKEKFVTGCINATQVANQEELSREKQDNKLHQRVLWRLIRELCSVKRCDFWLERGAGPRVAGAQPVL-LCLLAFIWFIVK---
>PRND_pca Procavia capensis (cape rock hyrax) Afrotheria fragment AY130772 ti|1293358170
PRND_ailMel    -MRKHLGGCWLAIVCVLLFSQLSAVKARGIKHRIKWNRKALPSTS-QVTEA-RTAEIRPGAFIRQGRKLD-IDLGAEGNRYYEANYWQFPDGIHYNGCS---EANVTKEKFVSGCINATRVANQEELSREKQDNRLYQRVLWRLVRELCSVKHCDFWLERGAGLRVGGDQALL-LCLLVFIWFIVK---
KPVTNPAHMTAAQVSDRRLGTFIRHGRKLDIDFGAEGNRYYEANYWLFPDGIHYDGCSDT
PRND_felCat    -MRKHLGGCWLAIVCVLLFSQLSAVKARGIKHRIKWNRKTLPSIS-QVTEA-HTAEIRPGAFIRQGRKLD-IDLGAEGNRYYEANYWQFPDGIHYNGCS---EANVTKEKFVTSCINATQVANQEELSREKQDHKLYQRVLWRLNRELLWSAHGNFGRERG----------------------------
NVTKELFVTNCINTTQAVNQEEFSREKQDNKLYQRILWRLIRELCSllglDFWPERVGGLffSLDQPVMLCLLVFIWFMLK*
PRND_equCab    -MRKHLGGCCLAIVCVLLFSQLPVVLSRGTKHRIKWNRKALPSTA-KVTEA-RVEEIRPGAFIRQGRKLN-INFGAEGNRYYEANYWQFPDEIHYNGCS---EANVTKEKFVISCINATQEANQEELSQEKQDDKLYQRILWRLISELCSVKHCDFGLESGTGLRVTMDQPVL-LCLLVFIWFIVK---
 
PRND_tapTer    --------------------------------------KALPSTS-KVTEA-HTAEIRPGAFIRQGRKLN-IDFGAEGNRYYEANYWQFPDEIHYNGCS---EANVTKEKFVISCINATQAENQEELSREKQDDKLHQRILWRLIRELCSV--------------------------------------
>PRND_ete Echinops telfairi Madagascar lesser tenrec Afrotheria 10,323,158 seq
PRND_sorAra    -MRKHLG-WCLAIACVLLLCQVPAAQARGIKHRIKWGRKAPPSTP-QVTEA-RVAEIRPGAFIRQGRKLN-LNLGGEDKRYYDAYYWQFPDGIHYNGCS---SANVTREKFISGCINATRAANQEELSREKHD-KLYQRVLWRLVRELCSLKRCDFWSERGAGLQVTVDQLMM-FCLLAFTWFIMK---
MRKHLGAGWLALACVLLFGHLSVVPARGIKHRIKWNRKTLPSTAHVTEARVSVTRPGAFV
PRND_eriEur    -MRKHLGGWWLAIVCVLFFSQLSAVKARGIKHRFKWNRKALPSTN-HVTEA-QVSEIRPGAFIRQGTKLD-IDLGAEANRYYEANYWQFPDGIHYNGCS---EVNVTKAKFIASCINATHSANQEELSREKHD-KLYQRVLWRLVRELCSLKRCDFWSERGAGLQVTVDQLMM-FCLLAFTWFIMK---
RHGQKLDVDLGADGNRYYEAHYWQFPDGIHYDGCSDANVTREMLVTRCINATQAANQAEF
PRND_cynSph    --------------------------------------KTLPSPSSHVTES-QTAEMRPGAFVKQGRKLN-IDFGDEGNRYYEAHYWEFPDGIYYDACS---KANVTKEKFVTSCINATQAVNQEELSQEKQDKLLHQRILWQLIRELCSV--------------------------------------
SAPPRDQQDSRLHQRVLWRLIRELCSAKRCDFWLEGAGASRAGLDQPPVLLGLLVLLGLTVK*
PRND_bosTau    -MRKHLGGCWLAIVCILLFSQLCSVKARGIKHRIKWNRKVLPSTS-QVTEA-RTAEIRPGAFIKQGRKLD-IDFGVEGNRYYEANYWQFPDGIHYNGCS---KANVTKEKFITSCINATQAANQEELSREKQDNKLYQRVLWQLIRELCSTKHCDFWLERGAGLRVTLDQPMM-LCLLVFIWFIVK---
 
PRND_oviAri    -MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKVLPSTS-QVTEA-HTAEIRPGAFIKQGRKLD-INFGVEGNRYYEANYWQFPDGIHYNGCS---EANVTKEKFVTSCINATQVANQEELSREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLQVTLDQPMM-LCLLVFIWFIVK---
>PRND_tma Trichechus manatus (Caribbean manatee) Afrotheria fragment
PRND_capHir    -MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKVLPSTS-QVTEA-HTAEIRPGAFIKQGRKLD-INFGVEGNRYYEANYWQFPDGIHYNGCS---EANVTKEKFVTSCINATQVANQEELSREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLQVTLDQPMM-LCLLVFIWFIVK---
KPLPNTPHVTAAQVSDARPGAFIRHGRKLDIDFGAEGNRYYEANYWQFPDGIHFDGCSEA
PRND_conTau    -MRKHLGGCWLAIVCVLLFSHLSSVKARGIKHRIKWNRKVLPSTS-QVTEA-RTAEIRPGAFIKQGRKLD-IDFGVEGNRYYEANYWQFPDGIHYNGCS---EPNVTKENFITSCINATQVANQEEMSREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLQVTLDQPMM-LCLLVFIWFIVK---
NVTKEMFVTSCINTTQAANQEEFSREKQDNKLYQRILWRLIRELCSV
PRND_girCam    -MRKHLGRCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKVLPSTS-QVTEA-HTAEIRPGAFIKQGRKLD-IDFGVEGNRYYEANYWQFPDGIHYNGCS---EANVTKEEFVTSCINATQAANQEELSREKQDNKLYQRILWRLIRELCSIKHCDFWLERGAGLQVTLDQPMM-LCLLVFIWFIVK---
 
PRND_ama      -MRKHLGGCWLAIACILLFSQLSSVKARGIKHRIKWNRKVLPSTS-QVTEA-HTAEIRPGAFIKQGRKLD-IDFGVEGNRYYEANYWQFPDGIHYNGCS---EANVTKEKFVTSCINATQVANQEELSREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLRVTLDQPMM-LCLLVFIWFIVK---
>PRND_mdo Monodelphis domestica doppel genomic revised +rassf2 -prnd -prnp
PRND_turTru    -MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKALPSTS-QVTEA-HTAEIRPGAFIRQGRKLD-INFGAEGNRYYEANYWQLPDGIHYNGCS---EANVTKEKFVTSCINATQAVNQEELSREKQDNSLYQRVLWQLIRELCSNKQCDFWLERGAGLRVTLDQPMM-LCLLVFIWFIVK---
MRRHLGICWIAIFFALLFSDLSLVKAKTTRQRNKSNRKGLQTNRTNPTTVQPSEKLQGTF
PRND_pseCra    -MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKALPSTS-QVTEA-HTAEIRPGAFIRQGRKLD-INFGAEGNRYYEANYWQFPDGIHYNGCS---EANVTKEKFVTSCINATQAVNQEELSREKQDNNLYQRVLWQLIRELCSNKQCDFWLERGAGLRVTLDQPMM-LCLLVFIWFIVK---
IRNGRKLVIDFGEEGNSYYATHYSLFPDEIHYAGCAESNVTKEVFISNCVNATRVINKLE
  PRND_phyCat    --------------------------------------KALPSTS-QVTEA-HTAEIVPGAFIKQGRKLD-IDFGAEGNRYYEANYWQFPDGIHYNGCS---EASVTKEKFVTSCINATQEVNQEELSLEKPDNKLYQRVLWRLIRELCSI--------------------------------------
PLEEQNISDIYSRILEQLIKELCALNYCEFRTGKGTGLRLSLDQYVMVYLVILTCLIVK*
PRND_susScr    -MRKHLGGRRWAIVCILLFSQLSEVKARGIKHRIKWNRKALPSTS-QVTEA-HTAEMRPGAFIKQGRKLD-IDFGAEGNRYYEANYWRFPDGIHYNGCS---EVNVTKEKFVTSCINTTQAANQEE-SHEKPDNKLYQRVLWRLIRELCSIKHCDFWLERGAGLRVTMDQPMM-LCLLVFIWLIVK---
 
PRND_borAnc    -MRKHLGAWWLAIVCILLFSHLSTVKARGIKHRIKWNRKALPSTA-QVTEA-HVAEIRPGAFIRQGRKLD-IDFGAEGNRYYEANYWQFPDGIHYNGCS---EANVTKEMFVTSCINATQAANQEEFSREKQDNKLHQRVLWRLIRELCSIKHCDFWLERGAGLRVTLDQPVM-LCLLVFIWFMVK---
>PRND_meu Macropus eugenii wallaby
PRND_dasNov    -MRKHLGGWRLAIVCVLLSGHLSMVKARGIKHRIKWNRKAAPGAA-QVTEA-RVAEQRPGAFVRQGRRLD-IDFGAEGNRYYEANYWQLPDGILYDGCA---EANVTKEALVAGCVNATQLANQAELAHEGQDT-LHRRVLGRLIRELCALKRCKFWPDRAAGPRLVRGAPVF-GGLLLLIWLLVR---
MRRHLGTWWTAIFFALLFSDLSLVKAKGTRQRNKSNRKSLQTNRVNPTTAQPSEILQGAF
PRND_choHof    -MRKHLGGWWLAAVFVLLVCHLSVAKARGIKHRIKWNRKALPSAA-QVTEA-RIAESRPGAFIKQGRKLD-IDFGAEGNKYYEANYWQFPDGIHYDGCS---EANVTKEVFVTGCINATQAANQAEFSREKHD-KLHQRVLWRLIRELCSVKHCDFWLERGGGLRLTVDQPVV-SACWFHLAYRE----
IRQGRKLSIDFGEEGNSYYETHYQLFPDEIHYVGCTESNVTKDIFISNCMNATHAVNNLE
PRND_losAfr    -MRKHLGAWWLAIAFVLLLSHLSMVTARGIKHRIKWNRKALPNTG-HVTAA-QVTETRPGAFIRHGRKLD-IDFGAEGNRYYEANYWQFPDGIHYDGCS---EANVTKEMFVTSCINTTQAANQEEFSR-KQDNKVYQRILWRLIRELCSVKHCDFWLDRGGGLRVSLDQPVM-LCLLVFIWFMVK---
TLEEKNASDIHSRVLEQLIKELCALKYCELETETGAGLKLSLDQSVMVYLVILTCLIVK*
PRND_eleMax    --------------------------------------KALPNTG-HVTAA-QVTETRPGAFIRHGRKLD-IDFGAEGNRYYEANYWQFPDGIHYDGCS---EANVTKEMFVTSCINTTQAANQEEFSREKQDNKVYQRILWRLIRELCSV--------------------------------------
 
PRND_proCap    --------------------------------------KPVTNPA-HMTAA-QVSDRRLGTFIRHGRKLD-IDFGAEGNRYYEANYWLFPDGIHYDGCS---DTNVTKELFVTNCINTTQAVNQEEFSREKQDNKLYQRILWRLIRELCSLLGLDFWPERVGGLFFSLDQPVM-LCLLVFIWFMLK---
>PRND_oan Ornithorhynchus anatinus platypus 42% to opposum 187 aa 4 cys in register
PRND_echTel    -MRKHLGAGWLALACVLLFGHLSVVPARGIKHRIKWNRKTLPSTA-HVTEA-RVSVTRPGAFVRHGQKLD-VDLGADGNRYYEAHYWQFPDGIHYDGCS---DANVTREMLVTRCINATQAANQAEFSRDQQDSRLHQRVLWRLIRELCSAKRCDFWLEGAGASRAGLDQPPVLLGLLVLLGLTVK---
MMTVRRRRRSGGARWLLVFLVLLSGDLSSLQARGPRPRNKAGRKPPPSNAGPDSPAPRPPAGARGTFIRRGGRLSVDFGPEGNGYY
PRND_triMan    --------------------------------------KPLPNTP-HVTAA-QVSDARPGAFIRHGRKLD-IDFGAEGNRYYEANYWQFPDGIHFDGCS---EANVTKEMFVTSCINTTQAANQEEFSREKQDNKLYQRILWRLIRELCSV--------------------------------------
QANYPLLPDAIVYPDCPTANGTREAFFGDCVNATHEANRGELTAGGNASDVHVRVLLRLVEELCALRDCGPALPTGPAPRPGPPGPPAALALLTLVLLGAQ*
PRND_monDom    -MRRHLGICWIAIFFALLFSDLSLVKAKTTRQRNKSNRKGLQTNRTNPTTV-QPSEKLQGTFIRNGRKLV-IDFGEEGNSYYATHYSLFPDEIHYAGCA---ESNVTKEVFISNCVNATRVINKLEPLEEQNISDIYSRILEQLIKELCALNYCEFRTGKGTGLRLSLDQYVM-VYLVILTCLIVK---
 
PRND_macEug    -MRRHLGTWWTAIFFALLFSDLSLVKAKGTRQRNKSNRKSLQTNRVNPTTA-QPSEILQGAFIRQGRKLS-IDFGEEGNSYYETHYQLFPDEIHYVGCT---ESNVTKDIFISNCMNATHAVNNLETLEEKNASDIHSRVLEQLIKELCALKYCELETETGAGLKLSLDQSVM-VYLVILTCLIVK---
>PRND_aca Anolis carolinensis weak but real! scaffold_1221:78,884-117,121 syntenic, oriented like PRNP but no larger
PRND_sacHar    -MRTPLETWWIAIFFTLLFSDLSLVKAKGIRQRNKSNRKSLQTNRANPTRE-QPSKILQGTFIRKGRKLS-INFGEEGNSYYEAHYKLFPDEIHYVGCA---ESSVTKDVFISNCVNVTHTANKLEPPEERNSSAIYSRVLEQLIKELCALKYCEFGMQIGAGFRLSLDQSMM-VYLMILAFFIVK---
MMQRPLVVAILLTALWSEVCLCRRVSGSANRRNKKTSTTTSAPKLQSSTTATTFQGNLCRGGQMI
PRND_ornana    MRRRSGGARWLLVFLVLLSGDLSSLQARGPRPRNKAGRKPPPSNAGPDSPAPRPPAGARGTFIRRGGRLS-VDFGPEGNGYYQANYPLLPDAIVYPDCP---TANGTREAFFGDCVNATHEANRGELTAGGNASDVHVRVLLRLVEELCALRDCGPALPTGPAPRPGPPGPPAALALLTLVLLGAQ---
DNMDLEPNDKVYYKANLKIFPDGLYYPNCSLLLQPNTTKEELVGECVNFTIASNKLNLSK
PRND_chrPic    MGRTRMVTCWMAMLLLVLCSNITLCR-RGSSSKKASQNKSPPPVNKPSPPTKKEPVKIPGTLCYTGQLLD-IKLEPEEAKYYTDNFKKFPDCIYYPRCFQSLEPNATKDTLVSECFNVTVSENKLDLPEGKNATSVYSRVMWQVISHLCAMEFCCQPCSLALSIHGSFGWLAMLC-LGSFISLTMQ---
GKDLSNTKERVMWVLIHHLCANESCGQPCPLLQNSGNLHYIGQVLTVFVGLIGCSFLSAK*
PRND_anocar    ---MMQRPLVVAILLTALWSEVCLCR-RVSGSANRRNKKTSTTTSAPKLQSSTTATTFQGNLCRGGQMIDNMDLEPNDKVYYKANLKIFPDGLYYPNCSLLLQPNTTKEELVGECVNFTIASNKLNLSKGKDLSNTKERVMWVLIHHLCANESCGQPCPLLQNSGNLHYIGQVLTVFVGLIGCSFLSAK
 
PRND_pytMol    ----MWKNLLVVVLLAVLCSNVGLCR-RRSGPTRKWPEKTVS-------KSSTKSSTTLGNLCYGSEMIDNMILEANDTTFYKDNAKEFPNGLFYPNCSLPLQPKVSRETRTEECVDFIIASSNLTLPNGKNASDPSKRVMWLVINHLCASETCSLPCPGSSNVSSAHYFLPIL--MTALVGYSILATR
>PRND_xtr Xenopus tropicalis frog 182 aa single exon 2 cDNAs odd unbalanced cysteines syntenic turtle-prnp like, no laevis
PRND_xenTro    MGRQNLFSCLILLLLILYCS-LSSPR-RAASSKKI--SKTTDLSRGAKRRPKVTNSPALGDLSFRGRALNVNFNLTEESELYTANLYSFPDGLYYPRPAH-LSGAGGTDEFISGCLNTTIERNKVWISEDDEEGDIYMSVATQVLQFLCMENYVKPTNGAVTCTGGLWVFIGVMHFFFLFRKGD-----
MGRQNLFSCLILLLLILYCSLSSPRRAASSKKISKTTDLSRGAKRRPKVTNSPALGDLSFRGRALNVNFNLTEESELYTANLYSFPDGLYYPR
                                                      *                    *    *  *          **      ***  *  *        *      * * *  *                        **                                       
PAHLSGAGGTDEFISGCLNTTIERNKVWISQLEDDEEGDIYMSVATQVLQFLCMENYVKPTNGAVTCTGGLWVFIGVMHFFFLFRKGD*
</pre>
<pre>
>PRND_aca Anolis carolinensis dna sequence
atgatgcagagacctctggtagtagccatccttttgacagccctatggagcgaggtctgtctctgtcggcgagtgagcgg
atctgcaaataggcggaataagaagacttccaccaccacaagtgctcccaaacttcaaagctcaaccacagccacaacct
tccaaggaaatctttgtcgtggtggtcaaatgattgacaatatggacctcgagccaaatgacaaagtctattacaaggca
aacctgaagattttcccagatggactttattatcccaactgttccttgcttctgcagcccaacacgaccaaagaagagct
cgttggtgaatgcgtcaatttcaccattgcatcaaataagttgaacctatctaaaggcaaggatttgagcaacacaaagg
agagggtgatgtgggtcttgattcatcacttgtgtgcaaatgagtcgtgcggtcagccttgccctttgctccaaaactct
ggaaatctccactatattggccaagtactcactgtatttgttggcctaattggttgctcttttctttctgcaaaataa
</pre>


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

Latest revision as of 15:15, 4 February 2012

Dating doppel: missing from bird and fish genomes -- but present in marsupial, lizard and frog

The prion and doppel genes represent a local tandem duplication that has descended intact in most lineages with the two genes remaining adjacent and unpseudogenized (though both spawned retroposed pseudogenes in later lineages). When did this gene duplication take place, did it correlate with or facilitate an evolutionary advantage, and how have the (largely unknown) normal functions of the original gene since diverged? Retention of either copy is already somewhat puzzling in view of viability of PRNP knockouts, indeed PRNP/PRND double knockouts.

The strikingly weak homology between prion and doppel -- below 30% identity within-species even trimming to conserved core -- suggests either an ancient duplication (lamprey era?) followed by symmetric divergence at more or less average rates, or alternatively a recent duplication (tetrapod era?) followed by rapid asymmetrically fast evolution on the doppel side as it neofunctionalized or subfunctionalized to a secondary function of the unduplicated gene. These possibilities can be distinguished by looking at earlier diverging species that bracket date on the duplication event.

If the duplication is old, then doppel should be found in various draft vertebrate genomes now available -- 34 mammals (see Genome completion status) plus chicken, lizard, frog, zebrafish, tetraodon, fugu, medaka, and stickleback. If synteny (gene order and orientation) are conserved, doppel will lie between PRNP and RASSF2, allowing highly diverged forms to be recognized by blast focused to that intergene region that otherwise might be lost among whole-genome match debris). Synteny and weak blast support are hopefully supplemented by conservation of internal signatures such as signal peptide, post-translationally modified arginine, disulfides, glycosylation sites, alpha helices, short beta sheet (YMLG in human), and GPI attachment.

Repeat structure is trickier to use because it has been totally lost in all PRND (at the time of duplication?) and in PRNP varies from wildly expanded in fish, biphasic hexapeptide in frog, turtles, birds, and lizards to decapeptide (platypus), nonapeptide (marsupial), or octapeptide (placentals) as discussed elsewhere Prion repeat evolution. Further, the number of observed repeats varies markedly across individuals (sometimes pathologically), an effect seen from birds to mammals. It is an unstable coding region of very high GC subject to frequent replication slippage with new variants constantly arising. There is no wild type allele, only a choice within population variants. This requires reconstructed ancestral nodes to consist of a reconstructed population. Consequently the region is not strictly speaking homologous across species and is only inappropriately included in orthologous alignments. The normal function if any is unknown; it cannot be assumed that a single function holds across species (knockins have no complementation assay). Thus the distribution of functions across PRNP and PRND must address possibly non-uniform function in PRNP across species.

PRND may never have been able to fully complement PRNP. Not only has the repeat region been lost (most parsimoniously at, or shortly after, duplication), but the two genes are asymmetrically positioned with respect to upstream promoters and regulatory elements of the original single gene, ie PRND is in the rain shadow of PRNP. After considerations involving dating and removing subsequently accrued retroposons, upstream non-coding elements were too far removed from the PRNP start codon in the ancestral genome to have been included in the original duplication. PRND must then have been transcribed by read-through (as seen today in rare mouse transcripts) which would have given it appropriate developmental and tissue expression from the get-go, perhaps at a reduced level that mitigated gene dosage while allowing more rapid divergence. In this asymmetric scenario, PRND only later developed transcription control regions in the intergenic region that could separately modulate expression.

Tandem gene duplications are thus quite different from large segmental (or whole genome) duplications. They require further stratification depending on whether parallel or inverted, whether inclusive or not of upstream regulatory regions, and whether or not in comparable euchromatin environments. Subsequent history is also important: PRNP and PRND have remained largely unperturbed but other tandem gene duplications have been followed by much later (thus lineage-specific) secondary events such as further tandem expansion, separating block inversions, translocation of one copy elsewhere, and deletion. Such events accrue roughly in proportion to elapsed time.

Consequently older tandem gene duplications tend to have unique histories, undercutting any program to develop sweeping theories. Rate histories must speak to a single timeline (of reconstructed ancestral nodes leading to a fixed species) rather than to repeatedly bifurcated timelines of phylogenetic tree data that reference increasingly incomparable clades. The history of the PRNP/PRND tandem duplication below will illustrates that.

PRNP sequences are available at GenBank from over 100 species of placental mammal. Dozens more can be extracted from genome projects in various stages of completion. The lesser effort expended on PRND and its much rarer transcripts conspire with rapidly weakening percent identity to make advanced bioninformatic techniques necessary as pipeline annotation collapses.

The brushtail opossum (Trichosurus vulpecular) prion gene sequence was determined in 1995. It conserves structural elements overall but presents various anomalies such as nonapeptide repeats. Its sequence can be used as query at the UCSC genome browser to locate a second complete marsupial PRNP sequence from Monodelphis domestica. Monodelphis domestica PRND is located next to PRNP in the same orientation in a gapless region of the assembly, left- and right-flanked by syntenically appropriate genes. A third marsupial sequence (Macropus eugenii) is available from unassembled NCBI trace archives; full length PRNP and PRND sequences are readily covered there by trace blastn using opossum query, though synteny cannot be pursued. Marsupials have had longer to diverge than placental mammals; the two 'opossums' here are not closely related, Didelphimorphia vs Diprotodontia. Paired rate studies thus await PRND from Trichosurus vulpecular and a fossil calibration of an overall molecular clock for marsupial divergence.

Monotreme represents an important earlier divergence. PRNP and PRND can be recovered from the newly released assembly of the platypus genome, Ornithorhynchus anatinus. This species, which diverged after birds but before the Theran split, has a PRNP decapeptide x 4 repeat (rather than a bird- or turtle-like hexapeptide. However its sequence, PQGGGASWGH, is unusual for its glutamine in second position and terminal histidine (reverse of usual mammal residues). In other respects it is conventional. Unfortunately neither sequence is available for echidna; these could be easily acquired because both genes consist of a single short coding exon.

Within placental mammals, doppel homology runs at about 85% identity but this drops off to 48% relative to marsupial and 41% in platypus, indicating (relative to global proteomes) a fast-evolving protein not yet a pseudogene in any lineage (though it spawned 'processed' pseudogenes in kangaroo rat and stem xenarthra). Indeed, with the density of PRNP gene sequences in placentals and the mammalian phylogenetic tree topology finally determined, clade-specific rate variations could be pursued in unusual detail, along with any correlated doppel evolution. The ancestral boreoeuthere PRND and PRNP sequences provided below could facilitate that quest by providing non-roundtrip rates over a fixed 85 myr time interval. The ancestral sequences have a meagre 21% identity.

The chicken genome is gap-free in this area and retains mammalian gene order and orientation (RASSF2- PRNP+ SCL23A-). However, no dopple gene (nor evidence for a decayed pseudogene) occurs in chicken in the expected position despite various high-sensitivity blast probes (reconstructed ancestral doppel, anole PRND). If prion gene duplication occurred prior to chicken divergence, then doppel has decayed to an unrecognizable pseudogene, translocated to region of gappy coverage, or deleted. The other bird genome underway, Taeniopygia guttata (finch), also lacks PRND. The intergenic region where PRND should lie, between PRNP and RASSF2, consists in chicken of a meagre 529 bp vs 122,057 bp in human, establishing a large indel has occured.

Very recently, a lizard genome became available, Anolis carolinensis. Lizards are a sister group to birds. Using specialized methods, a full length PRND gene can be located in expected syntenic position and validated by retained internal signatures despite an exceedingly very weak blast match.

Similarly the diploid frog, Xenopus tropicalis, has an unmistakable doppel gene at expected syntenic position and orientation. Some sequence uncertainty exists because of assembly issues and frameshifts in the two supporting ESTs. No doppel can be found in the (non-genomic) tetraploid frog, Xenopus laevis, though it has two actively transcribed PRNP genes that differ slightly in the repeat-like region as well at a few individual amino acids. There may be two in-paralog doppels in this species, depending on the relative timing of PRNP duplication and the tetraploidization event..

These results have a simple parsimonious explanation: the PRND duplication predated amphibian divergence, it was retained in all lineages except birds, where a lineage-specific deletion occured bird clade. Crocodile sequencing of this region could further refine the date of this event.

However nothing prevents homoplasy of tandem duplications and indeed we shall see this in teleost fish. On the contrary, the observation that both copies of a given duplication can be useful over billions of year of branch length supports the likelihood of it happening again in a lineage not participating in the original duplication. Here lizard and frog doppel queries retrieve solely mammalian and turtle PRND genes when back-blasted against the GenBank non-redundant nucleotide division. Both lack the repeat region and retain some internal diagnostic doppel signatures though not the second disulfide bond. This argues against the idea of multiple independent duplications of the prion gene in lizard and frog distinct from a later lineage-specific duplication in mammals (with birds then never having a PRND to delete).

Prnd align.png

The prion gene in teleost fish has radically diverged from its mammalian counterpart especially in the repeat region but remains recognizable via various conserved internal features, residual synteny, and its weak alignment. Fugu has a second PRNP gene on a different chromosome (presumably resulting from the whole genome duplication in Teleostei) plus an apparent novel tandem duplication that resembles PRNP rather than PRND. Coelocanth genome has been proposed but not begun -- that could further refine the timing of tetrapod PRND duplication.

As it stands, that event occurred after teleost fish divergence but before that of amphibians, say 400 million years ago. The prion gene clearly represents the ancestral form and presumably ancestral function, ie, a doppel-like ancestor did not duplicate to a second gene that become PRNP. No counterpart of PRNP can be located in the initial release of the chondrichthyian genome, Callorhinchus milii, but that will soon be finished to higher coverage and regional assembly. PRNP is most likely an ancient gene that simply has become unrecognizable.

Doppels are evolving noticeably faster than prions but have not become pseudogenes in any species investigated to date. (Very recent pseudogenes that have not yet acquired internal stop codons or loss of deeply invariant residues are difficult to detect.) It must be remembered that PRNP's globular region lies within the most slowly evolving quartile of mammalian genes. As a representative example, human/dog proteins have 78% identity for PRND but 87% for PRNP. A reconstructed ancestral mammal sequence for PRND shows no sign whatsoever of converging to a PRNP-like sequence, percent identity ancester-to-ancestor remains in the mid-20's. Since this uses up 100 million years of the 400 available, doppel may have evolved more drastically at an earlier time, perhaps soon after the duplication event.

The most economical explanation of the data is that the slow evolving prion gene retains the lion's share of ancestral functions whereas doppel has a narrow new but possibly related function with limited and specialized expression in uncommon cell types, yet one important enough for longterm gene retention. Over longer evolutionary time spans, we can't be sure either gene really functions identically in all species.

To further investigate the co-evolution of PRNP and PRND, it is imperative to obtain additional pairs of gene sequences from a phylogenetically representative sample of species, which here means echidna, turtles, and more lizards and amphibians. PRNP tends to be over-sampled within Artiodactylia, especially Bovidae. Doppel remains very poorly represented at dbEST even in much-studied mammals with enriched libraries of tissues like testis where doppel is known to be transcribed. Consequently additional doppel sequences will not drop out as byproducts of transcriptome projects.

However a respectable number of doppel sequences have accumulated. In addition to genome projects, van Rheede and coworkers sequenced nine doppels from important early diverging clades of placental mammals. PRND from the chimpanzee genome has special interest for evaluating known human doppel polymorphisms to determine "wildtype" human. Macaque doppel also exhibits the 2 amino acid deletion seen in human at position 122-123, showing this event predated old world monkey divergence. In fact that event can be precisely timed to the stem lying between tarsier and new world monkey divergence and shown highly non-homoplasic.

Ancestral length and PRND indels

Here an interesting loss of 2 residues helps define primates from new world monkeys on. Other indels in this region have limited phylogenetic interest because of homoplasy -- support for a hedgehog and shrew sister relation to the exclusion of other laurasiatheres is undercut by similar deletion in kangaroo rat, mouse lemur and pika. 

prnd_hsa anqgefq--kpdnklhqqvlwrlvqelcs  homo sapiens (human)
prnd_ptr anqgefq--kpdnklhqqvlwrlvrelcs  pan troglodytes (chimp)
prnd_ggo anqgefh--kpdnklhqqvlwrlvrelcs  gorilla gorilla (gorilla)
prnd_ppy anqgefq--kpdnklhqqvlwrlvqelcs  pongo pygmaeus (orang_sumatran)
prnd_nle anqgefq--kpdnklhqrvlwrlvrelcs  nomascus leucogenys (gibbon)
prnd_mml enqgefq--kpdnklhqrvlwrlvqelcs  macaca mulatta (rhesus)
prnd_pha anqgefq--kpdnklhqrvlwrlvqelcs  papio hamadryas (baboon)
prnd_cja anqaefq--kpdnklhqrvlwrlvqelcs  callithrix jacchus (marmoset_nwm)
prnd_tsy anaaerprearddplhqrvlgrlvrelcs  tarsius syrichta (tarsier)
prnd_oga anqaefsrekqdnklhqrilwrlirelcs  otoleumur garnetti (bushbaby)
prnd_mmr anqaefarekqd-klherilwrltrelcs  microcebus murinus (mouse_lemur)
prnd_tbe anqaefskekqdnklyqrvlwrlikelcs  tupaia belangeri (tree_shrew)
prnd_ocu anqgefsrekqdnklhqrvlwrlikelcs  oryctolagus cuniculus (rabbit)
prnd_opr anqgefsrekq-nklhqrvlwrlikelcs  ochotona princeps (pika)
prnd_dor anqaefaremqd-kfyqrvlwrltkelca  dipodomys ordii (kangaroo_rat)
prnd_str anqaefsrekqdnklhqrvlwrlikelcs  spermophilus tridecemlineatus (ground_squirrel)
prnd_rno anqaefsrekqdsklhqrvlwrlikeics  rattus norvegicus (rat)
prnd_mmu anqaefsrekqdsklhqrvlwrlikeics  mus musculus (mouse)
prnd_cpo anqaefsrekqdnklhqrilwrlikelcs  cavia porcellus  (guinea_pig)
prnd_sar anqeelsrekhd-klyqrvlwrlvrelcs  sorex araneus (shrew)
prnd_eeu anqeelsrekhd-klyqrvlwrlvrelcs  erinaceus europaeus (hedgehog)
prnd_cfa anqeelsrekqdnklhqrvlwrlirelcs  canis familiaris (dog)
prnd_fca anqeelsrekqddklyqrvlwrlnr-ecs  felis catus (cat)
prnd_tte enqeelsrekqddklhqrilwrlirelcs  tapirus terrestris (tapir)
prnd_eca anqeelsqekqddklyqrilwrliselcs  equus caballus (horse)
prnd_mlu anqeelsqerpdnrlhrrilwrlvrelcs  myotis lucifugus (microbat)
prnd_csp vnqeelsqekqdkllhqrilwqlirelcs  cynopterus sphinx (bat)
prnd_oar anqeelsrekqdnklyqrvlwqlirelcs  ovis aries (sheep)
prnd_chi anqeelsrekqdnklyqrvlwqlirelcs  capra hircus (goat)
prnd_bta anqeelsrekqdnklyqrvlwqlirelcs  bos taurus (cow)
prnd_ttr vnqeelsrekqdnslyqrvlwqlirelcs  tursiops truncatus (dolphin)
prnd_ssc anqee-shekpdnklyqrvlwrlirelcs  sus scrofa (pig)
prnd_pcw vnqeelslekpdnklyqrvlwrlirelcs  physeter catodon (whale)
prnd_ban anqeefsrekqdnklhqrvlwrlirelcs  boreoeuthere ancestralis (boreoeuthere)
prnd_dno anqaelaherqd-tlhgrvlgrlirelca  dasypus novemcinctus (armadillo)
prnd_cho anqaefsrekhd-klhqrvlwrlirelcs  choloepus hoffmanni (sloth)
prnd_pcp vnqeefsrekqdnklyqrilwrlirelcs  procavia capensis (hyrax)
prnd_ete anqaefsapqqdsrlhqrvlwrlirelcs  echinops telfairi (tenrec)
prnd_ema anqeefsrekqdnkvyqrilwrlirelcs  elephas maximus (elephant)
prnd_laf anqeefsr-kqdnkvyqrilwrlirelcs  loxodonta africana (elephant)
prnd_tma anqeefsrekqdnklyqrilwrlirelcs  trichechus manatus (manatee)
prnd_mdo inklepleeqnisdiysrileqlikelca  monodelphis domestica (opossum)
prnd_meu vnnletleeknasdihsrvleqlikelca  macropus eugenii (wallaby)
prnd_oan anrgeltaggnasdvhvrvllrlveelca  ornithorhynchus anatinus (platypus)
prnd_aca snklnlskgkdlsntkervmwvlihhlca  anolis carolinensis (lizard)
prnd_xtr rnkvwisqleddeegdiymsvatqvlqflcm xenopus tropicalis (frog)

Phylogenetic distribution of available PRND sequences

11 primates (euarchonta)
 7 glires (rodents and rabbits)
16 laurasiatheres
 1 ancestral boreoeuthere
 2 xenarthrans
 5 aftrotheres
 2 marsupials
 1 platypus
 0 bird (gene deleted in chicken and finch)
 1 lizard
 1 amphibian

Reference collection of PRND sequences

Below 45 PRND doppel sequences from land vertebrates are provided. Most are complete and reliable, but others are fragmentary and no better than the ongoing genome project from which they were extracted (initially low coverage, perhaps a single applicable trace). The phylogenetic distribution is approximately half as extensive as for PRNP. Almost all species having an available PRND would also have an available PRNP. It would be very easy to extend PRND coverage since primer design presents no issues. The most interesting rare genomic event for PRND of any phylogenetic depth is the indel shown above. 

>PRND_homSap Homo sapiens (human) full
MRKHLSWWWLATVCMLLFSHLSAVQTRGIKHRIKWNRKALPSTAQITEAQVAENRPGAFIKQGRKLDIDFGAEGNRYYEANYWQFPDGIHYNGCSEANVTKEAFVTGCINATQAANQGEFQKPDNKLHQQVLWRLVQELCSLKHCEFWLERGAGLRVTMHQPVLLCLLALIWLTVK*

>PRND_ptanTro Pan trogdylotes (chimpanzee) full
MRKHLSWWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSTAQITEAQVAENRPGAFIKQGRKLDIDFGAEGNRYYEANYWQFPDGIHYNGCSEANVTKEVFVTGCIHATQAANQGEFQKPDNKLHQQVLWRLVRELCSLKHCEFWLERGAGLRVTMHQPVLLCLLAFIWLMVK*

>PRND_gorGor Gorilla gorilla (gorilla)
MRKHLSWWWLATVCMLFFSHLSAVQARGIKHRIKWNRKALPSTAQITEAQVAENRPGAFIKQGRKLDIDFGAEGNRYYEANYWQFPDGIHYNGCSEANVTKEVFVTGCINATQAANQGEFHKPDNKLHQQVLWRLVRELCSLKHCEWLERSAGLRVTMHQPVLLCLLAFIWLMMK*

>PRND_ponPyg Pongo pygmaeus (orangutan) shares 2 bp deletion unique to primates.
MKNHLSWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSTAQITEAPGAENRPGALSkQGRQLDIDFGTEGNRYYEANYWQFPDGIHYDGCSEANVTKEVFVTGCINATQAANQGEFQKPDNKLHQQVLWRLVQELCSLKHCEFWLERGAGLRVTMHQPVLLCLLAFIWLMVK*

>PRND_nomLeu Nomascus leucogenys (gibbon)
MRKHLSWWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSTAQITEAQVAENRPGGFIKQGRKLDIDFGAEGNRYYEANYWQFPDGIHYDGCSEANVTKEVFVTGCINATQAANQGEFQKPDNKLHQRVLWRLVRELCSLKRCEFWLERGAGLRVTMHQPVLLCLLAFIWLMVK*

>PRND_papHam Papio hamadryas (baboon)
MRKHLSWWWLATVCMLLFSHLSAVQTRGIKHRIKWNRKALPSTAQITEAQVAENRPGAFIKQGRKLDIDFGAEGNRYYEANYWQFPDGIHYNGCSEANVTKEAFVTGCINATQAANQGEFQKPDNKLHQQVLWRLVQELCSLKHCEFWLERGAGLRVTMHQPVLLCLLALIWLTVK*

>PRND_macMul Macaca mulata (macaque) full
MRQHLSRWWLATVCMLLLSHLSVVQARGIKHRIKWNRKALPSTAQITEAQVAENRPGAFIKQGRKLNIDFGAEGNRYYEANYWQFPDGIHYDGCSEANVTKEVFVTGCINATQAENQGEFQKPDNKLHQRVLWRLVQELCSLKRCEFWLERGAGLRVTMHQPVLLCLPAFVWLMV*

>PRND_calJac Callithrix jacchus (marmoset) new world monkey 89% 
MRKHLSGWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSAAQITEAQVAENRPGTFIKQGRKLDINFGAEGNRYYEANYWQLPDGIHYDGCSETNVTKEVFVTGCINATQAANQAEFQKPDNKLHQRVLWRLVQELCSLKRCEFWLERGAGFRVATHQPLLLCLLAFIWLMAK*

>PRND_tarSyr Tarsius syrichta (tarsier)
MRKPLGGWRLAVVCVLLLGLLSAARARGIKHRFKWNRKASPSAARVTEARVAESRPGAFIRRGRKLDIDFGAEGNKYYEANYWQFPDGIHYDGCSKANVTKELLVAGCINATHAANAAERPREARDDPLHQRVLGRLVRELCSAKHCDFWPERAAAPGTARARPGALLLVSRL

>PRND_micMur Microcebus murinus (mouse_lemur)
MRKHLGGWRPAIVFILLFSHLAVVKARGIKHRIKWNRKPLPSTVHITEALVAENRPGAFIKQGRKLDVDFGEEGNRYYEANYWQFPDGIHYDGCSDANVTKEVFVASCINATVAANQAEFAREKQDKLHERILWRLTRELCSVKRCEFWLERGAGLRVAEDCPTILSLLLLLWLLLR*

>PRND_tupBel Tupaia belangeri tree shrew 6.7 m tr frag
RALPSTAHITEARVAENRPGAFIRQGRKLDIDFGVEGNRYYEANYWQFPDGIHYDGCSEVNVTKEMFITSCINATQAANQAEFSKEKQDNKLYQRVLWRLIKELCSIKHCDFWLERGAGLRVTMHLPVMLCLLVFVWFVVK*

>PRND_musMus Mus musculus (mouse) full 
MKNRLGTWWVAILCMLLASHLSTVKARGIKHRFKWNRKVLPSSGGQITEARVAENRPGAFIKQGRKLDIDFGAEGNRYYAANYWQFPDGIYYEGCSEANVTKEMLVTSCVNATQAANQAEFSREKQDSKLHQRVLWRLIKEICSAKHCDFWLERGAALRVAVDQPAMVCLLGFVWFIVK*

>PRND_ratNor Rattus norvegicus (rat) full 
MKNRVGTWGLAILCLLLASHLSTVKARGIKHRFKWNRKVLPSSGQITEAQVAENRPGAFIKQGRKLDIDFGAEGNKYYAANYWQFPDGIYYEGCSEANVTKEVLVTRCVNATQAANQAEFSREKQDSKLHQRVLWRLIKEICSTKHCDFWLERGAALRITVDQQAMVCLLGFIWFIVK*

>PRND_cavPor Cavia porcellus (guinea pig) fragment AY130773 N-extended at traces 7,499,469 seq
MKTSLCVWALVCVLLQCHFSSVAARGIKHRIRWGRKPTPSPSQVTEARVAMTRPGAFIKEGHKLNIDFGAEGNRYYETNYWQFPDGIHYNGCSDTNVTKEVLVTSCINATQAANQAEFSREKQDNKLHQRILWRLIKELCSA

>PRND_dipOrd Dipodomys ordii (squirrel) pseudogene
ITEARYRENAQGPSSIKP--QADIDF--ERAQ*YEA*YWQFADGINYEGCSRRHVTKQMFVSRCINVTQAANQAEFAREMQD-KFYQRVLWRLTKELCAVKQCDFWLERGEGCPVAIVNRPAMLGLLLCMWFIL

>PRND_speTri Spermophilus tridecemlineatus (squirrel) full
MKKHLGTWGLAVVCVLLSTHLSAIKARGIKHRIKWNRKSVPSTVQITEAQVAQNPPGAFIKQGRKLHIDFGAEGNKYYEANYWQFPDGIYYDGCSEANVTKEVFIAKCINATQAANQAEFSREKQDNKLHQRVLWRLIKELCSVKHCDFWLEGGAGFQLSVDQPVMLCLLVFIWLMVK*

>PRND_oryCun Oryctolagus cuniculus (rabbit) revised complete from traces 8,968,713 sequences 75%
MRKHLGAWGLAIVCVLLFSHLPPAKARGIKHRIKWNRKALPSTAQITEAHVAENRPGTFIRQGRKLNIDFGPEGNKYYEANYWQFPDGVHYDGCSEGNVTKEAFVAKCVNATQAANQGEFSREKQDNKLHQRVLWRLIKELCSIKHCDFWLERGAGVQVGGEQPLVLGLLLCTWLLVK*

>PRND_ochPri Ochotona princeps (pika) full
MRKHLGGWGLAIVCVLLFSLLPTVKARGIKHRIKWNRKALPSTAQITEARVAENRPGTFIRQGQKLSIDFGPEGNKYYEANYWQFPDGIHYDGCSEGNVTKEVFVAKCINATQAANQGEFSREKQNKLHQRVLWRLIKELCSIKHCDFWLERGAGFPVTVGQPMVVLCLLIFTWVLVK*

>PRND_canfam Canis familiaris (dog) full 
MRKHLGGCWLAIVCVLLLSQLSAVEARGIKHRIKWNRKALPGTSQVTEARSAEIRPGAFIRQGRKLDIDLGPEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTGCINATQVANQEELSREKQDNKLHQRVLWRLIRELCSVKRCDFWLERGAGPRVAGAQPVLLCLLAFIWFIVK*

>PRND_ailMel Ailuropoda melanoleuca (panda) full 89% identical dog
MRKHLGGCWLAIVCVLLFSQLSAVKARGIKHRIKWNRKALPSTSQVTEARTAEIRPGAFIRQGRKLDIDLGAEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVSGCINATRVANQEELSREKQDNRLYQRVLWRLVRELCSVKHCDFWLERGAGLRVGGDQALLLCLLVFIWFIVK*

>PRND_felCat Felis catus (cat) improved fragment 8,248,053 traces now 9.2
MRKHLGGCWLAIVCVLLFSQLSAVKARGIKHRIKWNRKTLPSISQVTEAHTAEIRPGAFIRQGRKLDIDLGAEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTSCINATQVANQEELSREKQDhKLYQRVLWRLNREALLWSAHGNFGRERG

>PRND_equCab Equus caballus (horse)
MRKHLGGCCLAIVCVLLFSQLPVVLSRGTKHRIKWNRKALPSTAKVTEARVEEIRPGAFIRQGRKLNINFGAEGNRYYEANYWQFPDEIHYNGCSEANVTKEKFVISCINATQEANQEELSQEKQDDKLYQRILWRLISELCSVKHCDFGLESGTGLRVTMDQPVLLCLLVFIWFIVK*

>PRND_tapTer Tapirus terrestris (tapir) fragment
KALPSTSKVTEAHTAEIRPGAFIRQGRKLNIDFGAEGNRYYEANYWQFPDEIHYNGCSEANVTKEKFVISCINATQAENQEELSREKQDDKLHQRILWRLIRELCSV 

>PRND_sorAra Sorex araneus (shrew) Laurasiatheria; Insectivora 7.23M tr
MRKHLGWCLAIACVLLLCQVPAAQARGIKHRIKWGRKAPPSTPQVTEARVAEIRPGAFIRQGRKLNLNLGGEDKRYYDAYYWQFPDGIHYNGCSSANVTREKFISGCINATRAANQEELSREKHDKLYQRVLWRLVRELCSLKRCDFWSERGAGLQVTVDQLMMFCLLAFTWFIMK* 

>PRND_eriEur Erinaceus europaeus (hedgehog)10,952,642 seq complete
MRKHLGGWWLAIVCVLFFSQLSAVKARGIKHRFKWNRKALPSTNHVTEAQVSEIRPGAFIRQGTKLDIDLGAEANRYYEANYWQFPDGIHYNGCSEVNVTKAKFIASCINATHSANQEELSREKHDKLYQRVLWRLVRELCSLKRCDFWSERGAGLQVTVDQLMMFCLLAFTWFIMK*

>PRND_myoLuc Myotis lucifugus (microbat) full
MRKQLGGCCLAIVCVLLFSQLAAVQARGIKHRIKWNRKGAAPPSSSQVTEAQRVEMQLRPGAFIKHGRKLDIDFGAEANRYYEANYWQFPDEIHYNGCSSEANVTREKFVSGCINATQAANQEELSQERPDNRLHRRILWRLVRELCSVKHCDFWLENGAGLWVTVHRPVMPCLLVSIWFIVK*

>PRND_pteVam Pteropus vampyrus (macrobat) frameshifts frag
MRRQLGGCWLAIVCVLLFSQLSTVKARGIKHRTKWNR PCDRVS VTESQ GAFIKQGRK

>PRND_cynSph Cynopterus sphinx (bat) fragment
KTLPSPSSHVTESQTAEMRPGAFVKQGRKLNIDFGDEGNRYYEAHYWEFPDGIYYDACSKANVTKEKFVTSCINATQAVNQEELSQEKQDKLLHQRILWQLIRELCSV

>PRND_bosTau Bos taurus (cow) full 
MRKHLGGCWLAIVCILLFSQLCSVKARGIKHRIKWNRKVLPSTSQVTEARTAEIRPGAFIKQGRKLDIDFGVEGNRYYEANYWQFPDGIHYNGCSKANVTKEKFITSCINATQAANQEELSREKQDNKLYQRVLWQLIRELCSTKHCDFWLERGAGLRVTLDQPMMLCLLVFIWFIVK*

>PRND_oviAri Ovis aries (sheep) full 
MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKVLPSTSQVTEAHTAEIRPGAFIKQGRKLDINFGVEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTSCINATQVANQEELSREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLQVTLDQPMMLCLLVFIWFIVK*

>PRND_capHir Capra hircus (goat)
MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKVLPSTSQVTEAHTAEIRPGAFIKQGRKLDINFGVEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTSCINATQVANQEELSREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLQVTLDQPMMLCLLVFIWFIVK*

>PRND_conTau Connochaetes taurinus (wildebeest) EF192574
MRKHLGGCWLAIVCVLLFSHLSSVKARGIKHRIKWNRKVLPSTSQVTEARTAEIRPGAFIKQGRKLDIDFGVEGNRYYEANYWQFPDGIHYNGCSEPNVTKENFITSCINATQVANQEEMSREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLQVTLDQPMMLCLLVFIWFIVK*

>PRND_girCam Giraffa camelopardalis (giraffe) EF192572
MRKHLGRCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKVLPSTSQVTEAHTAEIRPGAFIKQGRKLDIDFGVEGNRYYEANYWQFPDGIHYNGCSEANVTKEEFVTSCINATQAANQEELSREKQDNKLYQRILWRLIRELCSIKHCDFWLERGAGLQVTLDQPMMLCLLVFIWFIVK*

>PRND_ama Antidorcas marsupialis (springbok) Bovidae; Antilopinae
MRKHLGGCWLAIACILLFSQLSSVKARGIKHRIKWNRKVLPSTSQVTEAHTAEIRPGAFIKQGRKLDIDFGVEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTSCINATQVANQEELSREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLRVTLDQPMMLCLLVFIWFIVK*

>PRND_turTru Tursiops truncatus (dolphin)
MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKALPSTSQVTEAHTAEIRPGAFIRQGRKLDINFGAEGNRYYEANYWQLPDGIHYNGCSEANVTKEKFVTSCINATQAVNQEELSREKQDNSLYQRVLWQLIRELCSNKQCDFWLERGAGLRVTLDQPMMLCLLVFIWFIVK*   
>PRND_pseCra Pseudorca crassidens (false killer whale) AP009417 
MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKALPSTSQVTEAHTAEIRPGAFIRQGRKLDINFGAEGNRYYEANYWQFPDGIHYNGCSEANVTKEKFVTSCINATQAVNQEELSREKQDNNLYQRVLWQLIRELCSNKQCDFWLERGAGLRVTLDQPMMLCLLVFIWFIVK* 

>PRND_phyCat Physeter catodon (sperm) whale middle fragment
KALPSTSQVTEAHTAEIVPGAFIKQGRKLDIDFGAEGNRYYEANYWQFPDGIHYNGCSEASVTKEKFVTSCINATQEVNQEELSLEKPDNKLYQRVLWRLIRELCSI

>PRND_susScr Sus scrofa (pig) full length ti|470951185 
MRKHLGGRRWAIVCILLFSQLSEVKARGIKHRIKWNRKALPSTSQVTEAHTAEMRPGAFIKQGRKLDIDFGAEGNRYYEANYWRFPDGIHYNGCSEVNVTKEKFVTSCINTTQAANQEESHEKPDNKLYQRVLWRLIRELCSIKHCDFWLERGAGLRVTMDQPMMLCLLVFIWLIVK* 

>PRND_lamPac Lama pacos (alpaca) wgs frag
MRKHLGGCWLALACVLLLSPLSAVKARGIKHRIRWNRRPLPSASQATEAYTAELRPG

>PRND_borAnc Boreoeuthere ancestralis (ancestral)
MRKHLGAWWLAIVCILLFSHLSTVKARGIKHRIKWNRKALPSTAQVTEAHVAEIRPGAFIRQGRKLDIDFGAEGNRYYEANYWQFPDGIHYNGCSEANVTKEMFVTSCINATQAANQEEFSREKQDNKLHQRVLWRLIRELCSIKHCDFWLERGAGLRVTLDQPVMLCLLVFIWFMVK*

>PRND_dasNov Dasypus novemcinctus (armadillo) pseudo frag
ANYWQLPDGILYDGCAEANVTKEALVAGCVNGHTAANQAELAHERQDTLHGRVLGRLIRELCALKRCKFWPDR

>PRND_dasNov Dasypus novemcinctus (armadillo)
MRKHLGGWRLAIVCVLLSGHLSMVKARGIKHRIKWNRKAAPGAAQVTEARVAEQRPGAFVRQGRRLDIDFGAEGNRYYEANYWQLPDGILYDGCAEANVTKEALVAGCVNATQLANQAELAHEGQDTLHRRVLGRLIRELCALKRCKFWPDRAAGPRLVRGAPVFGGLLLLIWLLVR*

>PRND_choHof Choloepus hoffmanni (sloth) single trace old dasypus pseudogene, ti|563245674 
MRKHLGGWWLAAVFVLLVCHLSVAKARGIKHRIKWNRKALPSAAQVTEARIAESRPGAFIKQGRKLDIDFGAEGNKYYEANYWQFPDGIHYDGCSEANVTKEVFVTGCINATQAANQAEFSREKHDKLHQRVLWRLIRELCSVKHCDFWLERGGGLRLTVDQPVVSACWFHLAYRE*

>PRND_losAfr Loxodonta africana (elephant) Afrotheria 176 aa revised/corrected
MRKHLGAWWLAIAFVLLLSHLSMVTARGIKHRIKWNRKALPNTGHVTAAQVTETRPGAFIRHGRKLDIDFGAEGNRYYEANYWQFPDGIHYDGCSEANVTKEMFVTSCINTTQAANQEEFSRKQDNKVYQRILWRLIRELCSVKHCDFWLDRGGGLRVSLDQPVMLCLLVFIWFMVK* 

>PRND_eleMax Elephas maximus (elephant) Afrotheria fragment 
KALPNTGHVTAAQVTETRPGAFIRHGRKLDIDFGAEGNRYYEANYWQFPDGIHYDGCSEANVTKEMFVTSCINTTQAANQEEFSREKQDNKVYQRILWRLIRELCSV

>PRND_proCap Procavia capensis (cape rock hyrax) Afrotheria fragment AY130772 ti|1293358170
KPVTNPAHMTAAQVSDRRLGTFIRHGRKLDIDFGAEGNRYYEANYWLFPDGIHYDGCSDTNVTKELFVTNCINTTQAVNQEEFSREKQDNKLYQRILWRLIRELCSllglDFWPERVGGLffSLDQPVMLCLLVFIWFMLK*

>PRND_echTel Echinops telfairi (tenrec) Afrotheria 10,323,158 seq
MRKHLGAGWLALACVLLFGHLSVVPARGIKHRIKWNRKTLPSTAHVTEARVSVTRPGAFVRHGQKLDVDLGADGNRYYEAHYWQFPDGIHYDGCSDANVTREMLVTRCINATQAANQAEFSAPPRDQQDSRLHQRVLWRLIRELCSAKRCDFWLEGAGASRAGLDQPPVLLGLLVLLGLTVK* 

>PRND_triMan Trichechus manatus (manatee) Afrotheria fragment
KPLPNTPHVTAAQVSDARPGAFIRHGRKLDIDFGAEGNRYYEANYWQFPDGIHFDGCSEANVTKEMFVTSCINTTQAANQEEFSREKQDNKLYQRILWRLIRELCSV

>PRND_monDom Monodelphis domestica (opossum) doppel genomic revised +rassf2 -prnd -prnp
MRRHLGICWIAIFFALLFSDLSLVKAKTTRQRNKSNRKGLQTNRTNPTTVQPSEKLQGTFIRNGRKLVIDFGEEGNSYYATHYSLFPDEIHYAGCAESNVTKEVFISNCVNATRVINKLEPLEEQNISDIYSRILEQLIKELCALNYCEFRTGKGTGLRLSLDQYVMVYLVILTCLIVK*

>PRND_macEug Macropus eugenii (wallaby) 
MRRHLGTWWTAIFFALLFSDLSLVKAKGTRQRNKSNRKSLQTNRVNPTTAQPSEILQGAFIRQGRKLSIDFGEEGNSYYETHYQLFPDEIHYVGCTESNVTKDIFISNCMNATHAVNNLETLEEKNASDIHSRVLEQLIKELCALKYCELETETGAGLKLSLDQSVMVYLVILTCLIVK*

>PRND_sacHar Sarcophilus harrisii (tasmanian_devil) single exon gene 77% macEug
MRTPLETWWIAIFFTLLFSDLSLVKAKGIRQRNKSNRKSLQTNRANPTREQPSKILQGTFIRKGRKLSINFGEEGNSYYEAHYKLFPDEIHYVGCAESSVTKDVFISNCVNVTHTANKLEPPEERNSSAIYSRVLEQLIKELCALKYCEFGMQIGAGFRLSLDQSMMVYLMILAFFIVK*

>PRND_ornana Ornithorhynchus anatinus (platypus) 42% to opposum 187 aa 4 cys in register
MMTVRRRRRSGGARWLLVFLVLLSGDLSSLQARGPRPRNKAGRKPPPSNAGPDSPAPRPPAGARGTFIRRGGRLSVDFGPEGNGYYQANYPLLPDAIVYPDCPTANGTREAFFGDCVNATHEANRGELTAGGNASDVHVRVLLRLVEELCALRDCGPALPTGPAPRPGPPGPPAALALLTLVLLGAQ*

>PRND_chrPic Chrysemys picta (painted_turtle) 
MGRTRMVTCWMAMLLLVLCSNITLCRRGSSSKKASQNKSPPPVNKPSPPTKKEPVKIPGTLCYTGQLLDIKLEPEEAKYYTDNFKKFPDCIYYPRCFQSLEPNATKDTLVSECFNVTVSLTENKLDLPEGKNATSVYSRVMWQVISHLCAMEFCCQPCSLALSIHGSFGWLAMLCLGSFISLTMQ*

>PRND_anocar Anolis carolinensis (lizard) weak but real! scaffold_1221:78,884-117,121 syntenic, oriented like PRNP but no larger
MMQRPLVVAILLTALWSEVCLCRRVSGSANRRNKKTSTTTSAPKLQSSTTATTFQGNLCRGGQMIDNMDLEPNDKVYYKANLKIFPDGLYYPNCSLLLQPNTTKEELVGECVNFTIASNKLNLSKGKDLSNTKERVMWVLIHHLCANESCGQPCPLLQNSGNLHYIGQVLTVFVGLIGCSFLSAK*

>PRND_pytMol Python molurus (python) AEQU010389504
MWKNLLVVVLLAVLCSNVGLCRRRSGPTRKWPEKTVSKSSTKSSTTLGNLCYGSEMIDNMILEANDTTFYKDNAKEFPNGLFYPNCSLPLQPKVSRETRTEECVDFIIASSNLTLPNGKNASDPSKRVMWLVINHLCASETCSLPCPGSSNVSSAHYFLPILMTALVGYSILATR

>PRND_xenTro Xenopus tropicalis (frog) 182 aa single exon 2 cDNAs odd unbalanced cysteines syntenic turtle-prnp like, no laevis
MGRQNLFSCLILLLLILYCSLSSPRRAASSKKISKTTDLSRGAKRRPKVTNSPALGDLSFRGRALNVNFNLTEESELYTANLYSFPDGLYYPRPAHLSGAGGTDEFISGCLNTTIERNKVWISQLEDDEEGDIYMSVATQVLQFLCMENYVKPTNGAVTCTGGLWVFIGVMHFFFLFRKGD*

>PRND_anaCar Anolis carolinensis dna query sequence
atgatgcagagacctctggtagtagccatccttttgacagccctatggagcgaggtctgtctctgtcggcgagtgagcgg
atctgcaaataggcggaataagaagacttccaccaccacaagtgctcccaaacttcaaagctcaaccacagccacaacct
tccaaggaaatctttgtcgtggtggtcaaatgattgacaatatggacctcgagccaaatgacaaagtctattacaaggca
aacctgaagattttcccagatggactttattatcccaactgttccttgcttctgcagcccaacacgaccaaagaagagct
cgttggtgaatgcgtcaatttcaccattgcatcaaataagttgaacctatctaaaggcaaggatttgagcaacacaaagg
agagggtgatgtgggtcttgattcatcacttgtgtgcaaatgagtcgtgcggtcagccttgccctttgctccaaaactct
ggaaatctccactatattggccaagtactcactgtatttgttggcctaattggttgctcttttctttctgcaaaataa
                                                     *                    *     *  *           **      ***   *  *        *       * * *   *                        **                                        
PRND_homSap    -MRKHLSWWWLATVCMLLFSHLSAVQTRGIKHRIKWNRKALPSTA-QITEA-QVAENRPGAFIKQGRKLD-IDFGAEGNRYYEANYWQFPDGIHYNGCS---EANVTKEAFVTGCINATQAANQGEF--QKPDNKLHQQVLWRLVQELCSLKHCEFWLERGAGLRVTMHQPVL-LCLLALIWLTVK---
PRND_ptanTro   -MRKHLSWWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSTA-QITEA-QVAENRPGAFIKQGRKLD-IDFGAEGNRYYEANYWQFPDGIHYNGCS---EANVTKEVFVTGCIHATQAANQGEF--QKPDNKLHQQVLWRLVRELCSLKHCEFWLERGAGLRVTMHQPVL-LCLLAFIWLMVK---
PRND_gorGor    -MRKHLSWWWLATVCMLFFSHLSAVQARGIKHRIKWNRKALPSTA-QITEA-QVAENRPGAFIKQGRKLD-IDFGAEGNRYYEANYWQFPDGIHYNGCS---EANVTKEVFVTGCINATQAANQGEF--HKPDNKLHQQVLWRLVRELCSLKHCE-WLERSAGLRVTMHQPVL-LCLLAFIWLMMK---
PRND_ponPyg    -MKNHLS-WWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSTA-QITEA-PGAENRPGALSKQGRQLD-IDFGTEGNRYYEANYWQFPDGIHYDGCS---EANVTKEVFVTGCINATQAANQGEF--QKPDNKLHQQVLWRLVQELCSLKHCEFWLERGAGLRVTMHQPVL-LCLLAFIWLMVK---
PRND_nomLeu    -MRKHLSWWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSTA-QITEA-QVAENRPGGFIKQGRKLD-IDFGAEGNRYYEANYWQFPDGIHYDGCS---EANVTKEVFVTGCINATQAANQGEF--QKPDNKLHQRVLWRLVRELCSLKRCEFWLERGAGLRVTMHQPVL-LCLLAFIWLMVK---
PRND_papHam    -MRKHLSWWWLATVCMLLFSHLSAVQTRGIKHRIKWNRKALPSTA-QITEA-QVAENRPGAFIKQGRKLD-IDFGAEGNRYYEANYWQFPDGIHYNGCS---EANVTKEAFVTGCINATQAANQGEF--QKPDNKLHQQVLWRLVQELCSLKHCEFWLERGAGLRVTMHQPVL-LCLLALIWLTVK---
PRND_macMul    -MRQHLSRWWLATVCMLLLSHLSVVQARGIKHRIKWNRKALPSTA-QITEA-QVAENRPGAFIKQGRKLN-IDFGAEGNRYYEANYWQFPDGIHYDGCS---EANVTKEVFVTGCINATQAENQGEF--QKPDNKLHQRVLWRLVQELCSLKRCEFWLERGAGLRVTMHQPVL-LCLPAFVWLMV----
PRND_calJac    -MRKHLSGWWLATVCMLLFSHLSAVQARGIKHRIKWNRKALPSAA-QITEA-QVAENRPGTFIKQGRKLD-INFGAEGNRYYEANYWQLPDGIHYDGCS---ETNVTKEVFVTGCINATQAANQAEF--QKPDNKLHQRVLWRLVQELCSLKRCEFWLERGAGFRVATHQPLL-LCLLAFIWLMAK---
PRND_tarSyr    -MRKPLGGWRLAVVCVLLLGLLSAARARGIKHRFKWNRKASPSAA-RVTEA-RVAESRPGAFIRRGRKLD-IDFGAEGNKYYEANYWQFPDGIHYDGCS---KANVTKELLVAGCINATHAANAAERPREARDDPLHQRVLGRLVRELCSAKHCDFWPERAAAPGTARARP---GALLLVSRL------
PRND_micMur    -MRKHLGGWRPAIVFILLFSHLAVVKARGIKHRIKWNRKPLPSTV-HITEA-LVAENRPGAFIKQGRKLD-VDFGEEGNRYYEANYWQFPDGIHYDGCS---DANVTKEVFVASCINATVAANQAEFAREKQD-KLHERILWRLTRELCSVKRCEFWLERGAGLRVAEDCPTI-LSLLLLLWLLLR---
PRND_tupBel    --------------------------------------RALPSTA-HITEA-RVAENRPGAFIRQGRKLD-IDFGVEGNRYYEANYWQFPDGIHYDGCS---EVNVTKEMFITSCINATQAANQAEFSKEKQDNKLYQRVLWRLIKELCSIKHCDFWLERGAGLRVTMHLPVM-LCLLVFVWFVVK---
PRND_musMus    -MKNRLGTWWVAILCMLLASHLSTVKARGIKHRFKWNRKVLPSSGGQITEA-RVAENRPGAFIKQGRKLD-IDFGAEGNRYYAANYWQFPDGIYYEGCS---EANVTKEMLVTSCVNATQAANQAEFSREKQDSKLHQRVLWRLIKEICSAKHCDFWLERGAALRVAVDQPAM-VCLLGFVWFIVK---
PRND_ratNor    -MKNRVGTWGLAILCLLLASHLSTVKARGIKHRFKWNRKVLPSSG-QITEA-QVAENRPGAFIKQGRKLD-IDFGAEGNKYYAANYWQFPDGIYYEGCS---EANVTKEVLVTRCVNATQAANQAEFSREKQDSKLHQRVLWRLIKEICSTKHCDFWLERGAALRITVDQQAM-VCLLGFIWFIVK---
PRND_cavPor    -MKTSLCVW--ALVCVLLQCHFSSVAARGIKHRIRWGRKPTPSPS-QVTEA-RVAMTRPGAFIKEGHKLN-IDFGAEGNRYYETNYWQFPDGIHYNGCS---DTNVTKEVLVTSCINATQAANQAEFSREKQDNKLHQRILWRLIKELCSA--------------------------------------
PRND_speTri    -MKKHLGTWGLAVVCVLLSTHLSAIKARGIKHRIKWNRKSVPSTV-QITEA-QVAQNPPGAFIKQGRKLH-IDFGAEGNKYYEANYWQFPDGIYYDGCS---EANVTKEVFIAKCINATQAANQAEFSREKQDNKLHQRVLWRLIKELCSVKHCDFWLEGGAGFQLSVDQPVM-LCLLVFIWLMVK---
PRND_oryCun    -MRKHLGAWGLAIVCVLLFSHLPPAKARGIKHRIKWNRKALPSTA-QITEA-HVAENRPGTFIRQGRKLN-IDFGPEGNKYYEANYWQFPDGVHYDGCS---EGNVTKEAFVAKCVNATQAANQGEFSREKQDNKLHQRVLWRLIKELCSIKHCDFWLERGAGVQVGGEQPLV-LGLLLCTWLLVK---
PRND_ochPri    -MRKHLGGWGLAIVCVLLFSLLPTVKARGIKHRIKWNRKALPSTA-QITEA-RVAENRPGTFIRQGQKLS-IDFGPEGNKYYEANYWQFPDGIHYDGCS---EGNVTKEVFVAKCINATQAANQGEFSREKQ-NKLHQRVLWRLIKELCSIKHCDFWLERGAGFPVTVGQPMVVLCLLIFTWVLVK---
PRND_canfam    -MRKHLGGCWLAIVCVLLLSQLSAVEARGIKHRIKWNRKALPGTS-QVTEA-RSAEIRPGAFIRQGRKLD-IDLGPEGNRYYEANYWQFPDGIHYNGCS---EANVTKEKFVTGCINATQVANQEELSREKQDNKLHQRVLWRLIRELCSVKRCDFWLERGAGPRVAGAQPVL-LCLLAFIWFIVK---
PRND_ailMel    -MRKHLGGCWLAIVCVLLFSQLSAVKARGIKHRIKWNRKALPSTS-QVTEA-RTAEIRPGAFIRQGRKLD-IDLGAEGNRYYEANYWQFPDGIHYNGCS---EANVTKEKFVSGCINATRVANQEELSREKQDNRLYQRVLWRLVRELCSVKHCDFWLERGAGLRVGGDQALL-LCLLVFIWFIVK---
PRND_felCat    -MRKHLGGCWLAIVCVLLFSQLSAVKARGIKHRIKWNRKTLPSIS-QVTEA-HTAEIRPGAFIRQGRKLD-IDLGAEGNRYYEANYWQFPDGIHYNGCS---EANVTKEKFVTSCINATQVANQEELSREKQDHKLYQRVLWRLNRELLWSAHGNFGRERG----------------------------
PRND_equCab    -MRKHLGGCCLAIVCVLLFSQLPVVLSRGTKHRIKWNRKALPSTA-KVTEA-RVEEIRPGAFIRQGRKLN-INFGAEGNRYYEANYWQFPDEIHYNGCS---EANVTKEKFVISCINATQEANQEELSQEKQDDKLYQRILWRLISELCSVKHCDFGLESGTGLRVTMDQPVL-LCLLVFIWFIVK---
PRND_tapTer    --------------------------------------KALPSTS-KVTEA-HTAEIRPGAFIRQGRKLN-IDFGAEGNRYYEANYWQFPDEIHYNGCS---EANVTKEKFVISCINATQAENQEELSREKQDDKLHQRILWRLIRELCSV--------------------------------------
PRND_sorAra    -MRKHLG-WCLAIACVLLLCQVPAAQARGIKHRIKWGRKAPPSTP-QVTEA-RVAEIRPGAFIRQGRKLN-LNLGGEDKRYYDAYYWQFPDGIHYNGCS---SANVTREKFISGCINATRAANQEELSREKHD-KLYQRVLWRLVRELCSLKRCDFWSERGAGLQVTVDQLMM-FCLLAFTWFIMK---
PRND_eriEur    -MRKHLGGWWLAIVCVLFFSQLSAVKARGIKHRFKWNRKALPSTN-HVTEA-QVSEIRPGAFIRQGTKLD-IDLGAEANRYYEANYWQFPDGIHYNGCS---EVNVTKAKFIASCINATHSANQEELSREKHD-KLYQRVLWRLVRELCSLKRCDFWSERGAGLQVTVDQLMM-FCLLAFTWFIMK---
PRND_cynSph    --------------------------------------KTLPSPSSHVTES-QTAEMRPGAFVKQGRKLN-IDFGDEGNRYYEAHYWEFPDGIYYDACS---KANVTKEKFVTSCINATQAVNQEELSQEKQDKLLHQRILWQLIRELCSV--------------------------------------
PRND_bosTau    -MRKHLGGCWLAIVCILLFSQLCSVKARGIKHRIKWNRKVLPSTS-QVTEA-RTAEIRPGAFIKQGRKLD-IDFGVEGNRYYEANYWQFPDGIHYNGCS---KANVTKEKFITSCINATQAANQEELSREKQDNKLYQRVLWQLIRELCSTKHCDFWLERGAGLRVTLDQPMM-LCLLVFIWFIVK---
PRND_oviAri    -MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKVLPSTS-QVTEA-HTAEIRPGAFIKQGRKLD-INFGVEGNRYYEANYWQFPDGIHYNGCS---EANVTKEKFVTSCINATQVANQEELSREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLQVTLDQPMM-LCLLVFIWFIVK---
PRND_capHir    -MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKVLPSTS-QVTEA-HTAEIRPGAFIKQGRKLD-INFGVEGNRYYEANYWQFPDGIHYNGCS---EANVTKEKFVTSCINATQVANQEELSREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLQVTLDQPMM-LCLLVFIWFIVK---
PRND_conTau    -MRKHLGGCWLAIVCVLLFSHLSSVKARGIKHRIKWNRKVLPSTS-QVTEA-RTAEIRPGAFIKQGRKLD-IDFGVEGNRYYEANYWQFPDGIHYNGCS---EPNVTKENFITSCINATQVANQEEMSREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLQVTLDQPMM-LCLLVFIWFIVK---
PRND_girCam    -MRKHLGRCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKVLPSTS-QVTEA-HTAEIRPGAFIKQGRKLD-IDFGVEGNRYYEANYWQFPDGIHYNGCS---EANVTKEEFVTSCINATQAANQEELSREKQDNKLYQRILWRLIRELCSIKHCDFWLERGAGLQVTLDQPMM-LCLLVFIWFIVK---
PRND_ama       -MRKHLGGCWLAIACILLFSQLSSVKARGIKHRIKWNRKVLPSTS-QVTEA-HTAEIRPGAFIKQGRKLD-IDFGVEGNRYYEANYWQFPDGIHYNGCS---EANVTKEKFVTSCINATQVANQEELSREKQDNKLYQRVLWQLIRELCSIKHCDFWLERGAGLRVTLDQPMM-LCLLVFIWFIVK---
PRND_turTru    -MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKALPSTS-QVTEA-HTAEIRPGAFIRQGRKLD-INFGAEGNRYYEANYWQLPDGIHYNGCS---EANVTKEKFVTSCINATQAVNQEELSREKQDNSLYQRVLWQLIRELCSNKQCDFWLERGAGLRVTLDQPMM-LCLLVFIWFIVK---
PRND_pseCra    -MRKHLGGCWLAIVCVLLFSQLSSVKARGIKHRIKWNRKALPSTS-QVTEA-HTAEIRPGAFIRQGRKLD-INFGAEGNRYYEANYWQFPDGIHYNGCS---EANVTKEKFVTSCINATQAVNQEELSREKQDNNLYQRVLWQLIRELCSNKQCDFWLERGAGLRVTLDQPMM-LCLLVFIWFIVK---
PRND_phyCat    --------------------------------------KALPSTS-QVTEA-HTAEIVPGAFIKQGRKLD-IDFGAEGNRYYEANYWQFPDGIHYNGCS---EASVTKEKFVTSCINATQEVNQEELSLEKPDNKLYQRVLWRLIRELCSI--------------------------------------
PRND_susScr    -MRKHLGGRRWAIVCILLFSQLSEVKARGIKHRIKWNRKALPSTS-QVTEA-HTAEMRPGAFIKQGRKLD-IDFGAEGNRYYEANYWRFPDGIHYNGCS---EVNVTKEKFVTSCINTTQAANQEE-SHEKPDNKLYQRVLWRLIRELCSIKHCDFWLERGAGLRVTMDQPMM-LCLLVFIWLIVK---
PRND_borAnc    -MRKHLGAWWLAIVCILLFSHLSTVKARGIKHRIKWNRKALPSTA-QVTEA-HVAEIRPGAFIRQGRKLD-IDFGAEGNRYYEANYWQFPDGIHYNGCS---EANVTKEMFVTSCINATQAANQEEFSREKQDNKLHQRVLWRLIRELCSIKHCDFWLERGAGLRVTLDQPVM-LCLLVFIWFMVK---
PRND_dasNov    -MRKHLGGWRLAIVCVLLSGHLSMVKARGIKHRIKWNRKAAPGAA-QVTEA-RVAEQRPGAFVRQGRRLD-IDFGAEGNRYYEANYWQLPDGILYDGCA---EANVTKEALVAGCVNATQLANQAELAHEGQDT-LHRRVLGRLIRELCALKRCKFWPDRAAGPRLVRGAPVF-GGLLLLIWLLVR---
PRND_choHof    -MRKHLGGWWLAAVFVLLVCHLSVAKARGIKHRIKWNRKALPSAA-QVTEA-RIAESRPGAFIKQGRKLD-IDFGAEGNKYYEANYWQFPDGIHYDGCS---EANVTKEVFVTGCINATQAANQAEFSREKHD-KLHQRVLWRLIRELCSVKHCDFWLERGGGLRLTVDQPVV-SACWFHLAYRE----
PRND_losAfr    -MRKHLGAWWLAIAFVLLLSHLSMVTARGIKHRIKWNRKALPNTG-HVTAA-QVTETRPGAFIRHGRKLD-IDFGAEGNRYYEANYWQFPDGIHYDGCS---EANVTKEMFVTSCINTTQAANQEEFSR-KQDNKVYQRILWRLIRELCSVKHCDFWLDRGGGLRVSLDQPVM-LCLLVFIWFMVK---
PRND_eleMax    --------------------------------------KALPNTG-HVTAA-QVTETRPGAFIRHGRKLD-IDFGAEGNRYYEANYWQFPDGIHYDGCS---EANVTKEMFVTSCINTTQAANQEEFSREKQDNKVYQRILWRLIRELCSV--------------------------------------
PRND_proCap    --------------------------------------KPVTNPA-HMTAA-QVSDRRLGTFIRHGRKLD-IDFGAEGNRYYEANYWLFPDGIHYDGCS---DTNVTKELFVTNCINTTQAVNQEEFSREKQDNKLYQRILWRLIRELCSLLGLDFWPERVGGLFFSLDQPVM-LCLLVFIWFMLK---
PRND_echTel    -MRKHLGAGWLALACVLLFGHLSVVPARGIKHRIKWNRKTLPSTA-HVTEA-RVSVTRPGAFVRHGQKLD-VDLGADGNRYYEAHYWQFPDGIHYDGCS---DANVTREMLVTRCINATQAANQAEFSRDQQDSRLHQRVLWRLIRELCSAKRCDFWLEGAGASRAGLDQPPVLLGLLVLLGLTVK---
PRND_triMan    --------------------------------------KPLPNTP-HVTAA-QVSDARPGAFIRHGRKLD-IDFGAEGNRYYEANYWQFPDGIHFDGCS---EANVTKEMFVTSCINTTQAANQEEFSREKQDNKLYQRILWRLIRELCSV--------------------------------------
PRND_monDom    -MRRHLGICWIAIFFALLFSDLSLVKAKTTRQRNKSNRKGLQTNRTNPTTV-QPSEKLQGTFIRNGRKLV-IDFGEEGNSYYATHYSLFPDEIHYAGCA---ESNVTKEVFISNCVNATRVINKLEPLEEQNISDIYSRILEQLIKELCALNYCEFRTGKGTGLRLSLDQYVM-VYLVILTCLIVK---
PRND_macEug    -MRRHLGTWWTAIFFALLFSDLSLVKAKGTRQRNKSNRKSLQTNRVNPTTA-QPSEILQGAFIRQGRKLS-IDFGEEGNSYYETHYQLFPDEIHYVGCT---ESNVTKDIFISNCMNATHAVNNLETLEEKNASDIHSRVLEQLIKELCALKYCELETETGAGLKLSLDQSVM-VYLVILTCLIVK---
PRND_sacHar    -MRTPLETWWIAIFFTLLFSDLSLVKAKGIRQRNKSNRKSLQTNRANPTRE-QPSKILQGTFIRKGRKLS-INFGEEGNSYYEAHYKLFPDEIHYVGCA---ESSVTKDVFISNCVNVTHTANKLEPPEERNSSAIYSRVLEQLIKELCALKYCEFGMQIGAGFRLSLDQSMM-VYLMILAFFIVK---
PRND_ornana    MRRRSGGARWLLVFLVLLSGDLSSLQARGPRPRNKAGRKPPPSNAGPDSPAPRPPAGARGTFIRRGGRLS-VDFGPEGNGYYQANYPLLPDAIVYPDCP---TANGTREAFFGDCVNATHEANRGELTAGGNASDVHVRVLLRLVEELCALRDCGPALPTGPAPRPGPPGPPAALALLTLVLLGAQ---
PRND_chrPic    MGRTRMVTCWMAMLLLVLCSNITLCR-RGSSSKKASQNKSPPPVNKPSPPTKKEPVKIPGTLCYTGQLLD-IKLEPEEAKYYTDNFKKFPDCIYYPRCFQSLEPNATKDTLVSECFNVTVSENKLDLPEGKNATSVYSRVMWQVISHLCAMEFCCQPCSLALSIHGSFGWLAMLC-LGSFISLTMQ---
PRND_anocar    ---MMQRPLVVAILLTALWSEVCLCR-RVSGSANRRNKKTSTTTSAPKLQSSTTATTFQGNLCRGGQMIDNMDLEPNDKVYYKANLKIFPDGLYYPNCSLLLQPNTTKEELVGECVNFTIASNKLNLSKGKDLSNTKERVMWVLIHHLCANESCGQPCPLLQNSGNLHYIGQVLTVFVGLIGCSFLSAK
PRND_pytMol    ----MWKNLLVVVLLAVLCSNVGLCR-RRSGPTRKWPEKTVS-------KSSTKSSTTLGNLCYGSEMIDNMILEANDTTFYKDNAKEFPNGLFYPNCSLPLQPKVSRETRTEECVDFIIASSNLTLPNGKNASDPSKRVMWLVINHLCASETCSLPCPGSSNVSSAHYFLPIL--MTALVGYSILATR
PRND_xenTro    MGRQNLFSCLILLLLILYCS-LSSPR-RAASSKKI--SKTTDLSRGAKRRPKVTNSPALGDLSFRGRALNVNFNLTEESELYTANLYSFPDGLYYPRPAH-LSGAGGTDEFISGCLNTTIERNKVWISEDDEEGDIYMSVATQVLQFLCMENYVKPTNGAVTCTGGLWVFIGVMHFFFLFRKGD-----
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