Variability in Prion Octapeptide Repeat Region

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).

repeat	variant	freq	example	repeat	variant	freq	example
r0	pqggggwgq	16	mandrill	r1	phgggwgq	28	kudu
r0	pqggg-wgq	6	sp. monkey
r0	sqggggwgq	1	kudu	r2	phgggwgq	26	sp. monkey
r0	pqsggtwgq	1	rat	r2	phggswgq	1	mouse
r0	pqsgg-wgq	1	night monkey	r2	phvggwgq	1	kudu
r0	pqgggtwgq	1	g.hamster
r0	pqgg-twgq	1	mouse	r3	phgggwgq	25	sp. monkey
r0	pqeggdwgq	1	greater kudu	r3	phggswgq	2	bc capuchin
				r3	phggg-gq	1	rat

r5	---	25	rabbit	r4	phggg-wgq	18	rabbit
r5	phggggwgq	2	bovine	r4	phggggwgq	7	pig
r5	phgggwgq	1	sq. monkey	r4	---	2	sp. monkey
				r4	phggg-wsq	1	rat

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.

Key	R0	R1	R2	R3	R4	R5	Species
PHGGGWGQ = 1	v9	1	v8	1	1g	-	greater kudu
PQGGGWGQ = 1q	1q	1	1	1	1	1	squirrel monkey
PHGGSWGQ = 1s	1q	1	1	1	1	-	marmoset
PHGGGGWGQ = 1g	v8	1	1s	1s	1	-	mouse
PQGGGGWGQ = 1qg	1q	1	1	1	1	-	rabbit
	1q	1	1	1	1	-	bs monkey
PQGGGTWGQ = v9	1q	1	1	1s	1	-	bc capuchin
PQEGGDWGQ= v9	1q	1	1	1	-	-	bh spider monkey
PQSGGTWGQ= v9	1qg	1	1	1	1	1g	bovine 1
SQGGGGWGQ= v9	1qg	1	1	1	1	-	mandrill
	1qg	1	1	1	1	-	colobus
PQGGTWGQ= v8	1qg	1	1	1	1	-	ce macaque
PQSGGWGQ= v8	1qg	1	1	1	1	-	presbytis
PHVGGWGQ= v8	1qg	1	1	1	1	-	gorilla
PHGGGWSQ= v8	1qg	1	1	1	1	-	human
	1qg	1	1	1	1	-	chimpanzee
PHGGGGQ = v7	1qg	1	1	1	1	-	orangutan
	1qg	1	1	1	1	-	pig
	1qg	1	1	1	1g	-	mule deer
	1qg	1	1	1	1g	-	sheep
	1qg	1	1	1	1g	-	bovine 2
	1qg	1	1	1	1g	-	polecat
	1qg	1	1	1	1g	-	mink
	1qg	1	1	1	-	-	green monkey
	v9	1	1	1	1	-	golden hamster
	v8	1	1	1	1	-	night monkey
	v9	1	1	v7	v8	-	rat
	v9	1	1	1	1	1g	greater 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.)
Nucleotide	Repeat	Sequence
160-186	R1	cctcagggagggggtggctggggtcag
187-210	R2	ccccatgga-----ggtggctggggccag
211-234	R3	cctcatgga-----ggtggctggggccag
235-258	R4	cctcaggga-----ggtggctggggtcag
259-282	R5	ccccagggt-----ggtggctggggtcag
283-309	R6	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