Variation across species of each octapeptide repeat
Variation within species of octapeptide repeats
Bovine octapeptide polymorphism
Faster mutation in hominoid prion during period of brain expansion

Variability within each Prion Octapeptide Repeat Region

Variability within each of the octapeptide repeat regions is tabulated for 28 species of placental mammals. Thus, for the second repeat R2, three amino acid sequence variations occur with frequencies 26, 1, and 1. It can be seen that the pre-repeat nonapeptide has the greatest variability (8 types) and the first repeat R1 the least (none).

repeatvariantfreqexamplerepeatvariantfreqexample
r0pqggggwgq16mandrillr1phgggwgq28kudu
r0pqggg-wgq6sp. monkey
r0sqggggwgq1kudur2phgggwgq26sp. monkey
r0pqsggtwgq1ratr2phggswgq1mouse
r0pqsgg-wgq1night monkeyr2phvggwgq1kudu
r0pqgggtwgq1g.hamster
r0pqgg-twgq1mouser3phgggwgq25sp. monkey
r0pqeggdwgq1greater kudur3phggswgq2bc capuchin
r3phggg-gq1rat
r5---25rabbitr4phggg-wgq18rabbit
r5phggggwgq2boviner4phggggwgq7pig
r5phgggwgq1sq. monkeyr4---2sp. monkey
r4phggg-wsq1rat


Variation in Octapeptide Repeats

Within a given species, repeats at the amino acid level are not always perfect. However, beyond simple variations on the main theme, only a few other minor variants are found. Using the key to read the table, we see that the line 1qg, 1, 1, 1, 1, 1g is interpreted as PQGGGGWGQ, PHGGGWGQ, PHGGGWGQ, PHGGGWGQ, PHGGGWGQ, PHGGGGWGQ for the bovine sequence.

KeyR0R1R2R3R4R5Species
PHGGGWGQ = 1v91v811g-greater kudu
PQGGGWGQ = 1q1q11111squirrel monkey
PHGGSWGQ = 1s1q1111-marmoset
PHGGGGWGQ = 1gv811s1s1-mouse
PQGGGGWGQ = 1qg1q1111-rabbit
1q1111-bs monkey
PQGGGTWGQ = v91q111s1-bc capuchin
PQEGGDWGQ= v91q111--bh spider monkey
PQSGGTWGQ= v91qg11111gbovine 1
SQGGGGWGQ= v91qg1111-mandrill
1qg1111-colobus
PQGGTWGQ= v81qg1111-ce macaque
PQSGGWGQ= v81qg1111-presbytis
PHVGGWGQ= v81qg1111-gorilla
PHGGGWSQ= v81qg1111-human
1qg1111-chimpanzee
PHGGGGQ = v71qg1111-orangutan
1qg1111-pig
1qg1111g-mule deer
1qg1111g-sheep
1qg1111g-bovine 2
1qg1111g-polecat
1qg1111g-mink
1qg111--green monkey
v91111-golden hamster
v81111-night monkey
v911v7v8-rat
v911111ggreater kudu 2

Bovine Prion octapeptide polymorphism shows a 24 bp insertion of nucleotides 211 to 234.

Cow Prion Variant
(Normal cow is missing R3.
The other known polymorphism in cows is at nucleotide 576 .. C to T transition, creating a HindII polymorphism), gtcaac to gtcaat (silent at amino acid level position191, 3rd position in asn.)
NucleotideRepeatSequence
160-186R1
cctcagggagggggtggctggggtcag
187-210R2
ccccatgga-----ggtggctggggccag
211-234R3
cctcatgga-----ggtggctggggccag
235-258R4
cctcaggga-----ggtggctggggtcag
259-282R5
ccccagggt-----ggtggctggggtcag
283-309R6
ccacagggaggtggaggctggggtcaa


New Primate sequences reported

Listserve 11.14.96

We still wait for Goldmann et al to post the cat prion sequence into Genbank (or publication) -- reported in 4 July 1996 Nature and used there to critique Southward's group.

A better practise is to post newly sequenced species, as completed, into Genbank as this Dutch group has done. Then scientists who have subscribed to SwissProt automatic alerting services, get the news in a timely fashion. The PNAS article has not come out, but the title suggests that prion evolutionary analysis supports the theory of punctuated equilibrium of Gould et al., that is, genes change most rapidly during times of rapid speciation and not during long lulls. Whatever, it is good to have these new sequences...

--------

Increased substitution rate in hominoid prion during period of brain expansion

Proc. Natl. Acad. Sci. U.S.A. (1996) In press
van der Kuyl, A.C., Dekker, J.T. and Goudsmit, J.
Alignment of the octapeptide repeat regions shows Cercocebus aterrimus has a very unusual 9 residue deletion that by rights should not function properly, , Colobus guereza has an asparagine to serine change in the post-repeat region. Otherwise, the octapeptide repeat regions are identical.

All five species use Met at "codon 129."

PQGGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGWGQ GGGTHSQW Theropithecus gelad gelada baboon U75383
PQGGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGWG -------- GGGTHNQW Cercocebus aterrimus . U75384
PQGGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGWGQ GGGTHNQW Cercocebus torquatus atys sooty mangabey U75385
PQGGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGWGQ GGGTHNQW Cercopithecus patas . U75388
PQGGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGWGQ GGGTHNQW Cercopithecus mona . U75386

 U75389 Colobus guereza

MLVLFVATWSDLGLCKKRPKPGGWNTGGSRYPGQGSPGGNRYPP
                     QGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQGGGTHSQWNKPSKPKTSM
                     KHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVD
                     QYSNQNNFVHDCVNITIKQHTVTTTTKGENFTETDVKMMERVVEQMCITQYEKESQAY
                     YQRGSSMVLFSSPPVILLISFLIFLIVG
------------
U75383 gelada baboon. Theropithecus gelada
           MLVLFVATWSDLGLCKKRPKPGGWNTGGSRYPGQGSPGGNRYPP
                     QGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQGGGTHNQWHKPSKPKTSMKHMAGAAA
                     AGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNF
                     VHDCVNITIKQHTVTTTTKGENFTETDVKMMERVVEQMCITQYQKESQAYYQRGSSIV
                     LFSSPPVILLISFLIFLIVG
-----------
 U75384  Cercocebus aterrimus.

MLVLFVATWSDLGLCKKRPKPGGWNTGGSRYPGQGSPGGNRYPP
                     QGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQGGGTHNQWHKPSKPKTSMKHMAGAAA
                     AGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNF
                     VHDCVNITIKQHTVTTTTKGENFTETDVKMMERVVEQMCITQYEKESQAYYQRGSSMV
                     LFSSPPVILLISFLIFLIVG
----------
U75385  sooty mangabey.  Cercocebus torquatus atys

  MLVLFVATWSDLGLCKKRPKPGGWNTGGSRYPGQGSPGGNRYPP
                     QGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQGGGTHNQWHKPSKPKTSM
                     KHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNEYEDRYYRENMYRYPNQVYYRPVD
                     QYSNQNNFVHDCVNITIKQHTVTTTTKGENFTETDVKMMERVVEQMCITQYEKESQAY
                     YQRGSSMVLFSSPPVILLISFLIFLIVG
------------
U75388  Cercopithecus patas. Cercopithecus patas

MLVVFVATWSDLGLCKKRPKPGGWNTGGSRYPGQGSPGGNRYPP
                 QGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQGGGTHNQWHKPSKPKTSM
                     KHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVD
                     QYSNQNNFVHDCVNITIKQHTVTTTTKGENFTETDVKMMERVVEQMCITQYEKESQAY
                     YQRGSSMVLFSSPPVILLISFLIFLIVG
------------
U75386  Cercopithecus mona

MLVLFVATWSDLGLCKKRPKPGGWNTGGSRYPGQGSPGGNRYPP
                 QGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQGGGTHNQWHKPSKPKTSM
                     KHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVD
                     QYSNQNNFVHDCVNITIKQHTVTTTTKGENFTETDVKMMERVVEQMCITQYEKESQAY
                     YQRGSSMVLFSSPPVILLISFLIFLIVG