HYB: Gene Change Possibility

below is an abstract of an article appearing in this month's Science
magazine (http://www.sciencemag.org). If you are interested in the full
article, I'd suggest going to the library or to the newsstand that may
carry Science, rather than looking for it online. If you do so online,
you'd need to be a subscriber to the site or pay $10 for the article.

The article talks about, I think, a change in a gene in mammals in that
the protein is not modified, but the action of the cellular mechanism
changes, while the mechanism itself appears to be unchanged.

I do not know how well this would translate to plants, if it does at
all, but it may help describe some of the things that you hybridizers
see when you make your crosses. I came across this in a short piece in
Science News magazine which, unfortunately, requires a subscription to
access the article, though there are some available for free each week
on their site (http://www.sciencenews.org).


A "Silent" Polymorphism in the MDR1 Gene Changes Substrate Specificity

Chava Kimchi-Sarfaty 1*, Jung Mi Oh 2*, In-Wha Kim 3, Zuben E. Sauna 3,
Anna Maria Calcagno 3, Suresh V. Ambudkar 3, Michael M. Gottesman 3*

1 Laboratory of Cell Biology, Center for Cancer Research, National
Cancer Institute, Bethesda, MD 20892, USA; Present address: Center for
Biologics Evaluation and Research, Food and Drug Administration, 29
Lincoln Drive, Room 316, Bethesda, MD 20892, USA.
2 Laboratory of Cell Biology, Center for Cancer Research, National
Cancer Institute, Bethesda, MD 20892, USA; College of Pharmacy, Seoul
National University, Seoul 140-742, South Korea.
3 Laboratory of Cell Biology, Center for Cancer Research, National
Cancer Institute, Bethesda, MD 20892, USA.


* To whom correspondence should be addressed.
Chava Kimchi-Sarfaty , E-mail: kimchi{at}cber.fda.gov
Jung Mi Oh , E-mail: jmoh{at}snu.ac.kr
Michael M. Gottesman , E-mail: mgottesman{at}nih.gov


Synonymous Single Nucleotide Polymorphisms (SNPs) do not change the
coding sequences, and, therefore, are not expected to change the
function of the protein in which they occur. Here, we report that a
synonymous SNP in the Multidrug Resistance 1 (MDR1) gene, part of a
haplotype previously linked to altered function of the MDR1 gene
product, P-glycoprotein (P-gp), nonetheless results in P-gp with altered
drug and inhibitor interactions. Similar mRNA levels and protein, but
altered conformations were found for wild-type and polymorphic P-gp. We
hypothesize that the presence of a rare codon, marked by the synonymous
polymorphism, affects the timing of co-translational folding and
insertion of P-gp into the membrane, thereby altering the structure of
substrate and inhibitor interaction sites.

\\Steve//

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