simple polymeric repeats

Caroline A Breitenberger cbreiten at
Tue Feb 9 16:54:14 EST 1993

I was pleasantly surprised to see Cassandra's post, as she
introduced a topic that is very timely for me.  A student in my lab
is working on a Neurospora crassa gene that is most likely involved
in mitochondrial gene expression, and which has 20 glutamines
interrupted by one glutamic acid.  When we send his sequence to
Genbank, we pick up lots of different genes containing poly(gln),
many of which are developmental regulators and/or transcription

Here are some, along with their GenBank ID:
Drosophila virilis "mastermind" (what a great name!)
       DROMASTM (GenBank Protein: DROMASTM_1)
Yeast glucose repression mediator protein
       SwissProt:  CYC8_YEAST
Drosophila virilis C/EBP protein
Drosophila melanogaster Prospero
       DROPROSPER (GP: DROPROSPER_1)  [See Vaessin et al., Cell 67,
941-954 (1991) - this gene has many different polymeric repeats.]

I am not sure whether any of the genes listed above use a single
codon to encode the repeated amino acid.  (I gather that is what
Cassandra is interested in.)  Our gene uses both gln codons in the
gln repeat, *suggesting* that it is the amino acid sequence that
matters, rather than the nucleotide sequence, and consistent with
the possibility that it is some sort of hydrophilic, hydrogen-bond-
forming linker or structural element.  We have not looked (yet) for
instability of the gln repeat in our gene.

In response to Steve Modena's gracious post, these are not Q-
linkers as described in Wootton and Drummond, Prot. Eng. 2, 535
(1989).  For one thing, we're not talking about "relatively rich in
glutamine, etc.", we're talking *exclusively* gln (or very nearly
so).  In addition, these authors point out regularly spaced
hydrophobic residues (4-5 amino acid periodicity) near the C-
terminus of the so-called Q-linker, which is clearly not the case

There are cases of repeated trinucleotides that are involved in
polymorphisms resulting in disease phenotypes, with myotonic
dystrophy (MD) being a well-known example.  [See Fu et al., Science
255, 1256 (1992).]  Fragile X syndrome and spinal and bulbar
muscular atrophy (SBMA) also involve trinucleotide repeat
polymorphisms.  In the case of SBMA, the polymorphic repeat is in
the androgen receptor mentioned in Cassandra's post and involves
amplification of a stretch of glutamines.  In both MD and fragile
X, the repeats are close to, but not in protein coding sequences. 
[See Caskey et al., Science 256, 784 (1992).]  So what does it all

Caroline Breitenberger, Assistant Professor
Departments of Biochemistry and Molecular Genetics
Ohio State University
Columbus, OH 43210-1292
Phone: 614-292-9473
FAX:   614-292-6773
email: caroline+ at

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