This is an oddity and
noteworthy. The malaria parasite is a
genetic outlier meaning that the layout of its DNA is so different that we
cannot use established methods to determine gene function. In this case they are forced to work with a
close relative to indirectly infer functionality and one wonders just how well
that might work.
We clearly need to develop more single
cell platforms to investigate the possible DNA variations available. This
is a little like discovering a library after working one’s way through a book
but also represents opportunity as it has shown the way to uncover information
already.
There is a grammar and even a
language here that should succumb to rational order eventually.
Researchers Discover Method to Unravel Malaria's Genetic Secrets
by Staff Writers
The parasite that causes malaria is a genetic outlier, which has
prevented scientists from discovering the functions of most of its genes.
Researchers at National Jewish Health and Yale University School of
Medicine have devised a technique to overcome the genetic oddity of Plasmodium
falciparum, the major cause of human malaria.
This new approach led them discover a new gene involved in lipid
synthesis, and opens the door to further genetic discovery for the entire
organism. This should foster a much greater understanding of the parasite, and
facilitate discovery of new medications for a disease that
infects more than 200 million people and kills nearly 700,000 every year.
"The malarial genome has been a black box. Our technique allows us
to open that box, so that we can learn what genes in the most lethal human
parasite actually do," said Dennis Voelker, PhD, Professor of Medicine at
National Jewish Health and senior author on the paper that appeared in the
January 2, 2012 , issue of the Journal of Biological Chemistry. "This
could prove tremendously valuable in the fight against a disease that has
become increasingly drug-resistant."
The genome of
P. falciparum was sequenced in 2002, but the actual functions of many of the
organism's genes have remained elusive. One of the primary methods for discovering
gene function is to copy a specific gene, insert it into a model organism that
is easy to grow, often the yeast Saccharomyces cerevisiae, then draw on the
incredible knowledge base about yeast and its abundant genetic variants to
discover how that inserted gene changes the organism's biology.
DNA is composed of building blocks with the shorthand designations
A,T,C and G. The genome of P. falciparum is odd because it is particularly
rich in A's and T's. Because of this A-T-rich nature, P. falciparum
genes generally do not function when they are inserted into other organisms.
As a result, scientists have been largely stymied when trying to understand the
functions of P. falciparum's genes.
It turns out, however, that P. falciparum has a close cousin, P.
knowlesi, which shares almost all its genes with P. falciparum, but with fewer
A's and T's. As a result, P. knowlesi genes function well
when inserted into yeast. Scientists can now insert P knowlesi genes into
yeast, discover their function, and then match them to corresponding genes in
P. falciparum, which reveals the function of the malarial parasite's genes.
"This technique could lead to an explosion in knowledge about
malaria and the parasite that causes it." said Dr. Voelker.
The researchers used the technique to discover a new gene involved in
the synthesis of lipids in cell membranes of P. falciparum. The gene,
phosphatidylserine decarboxylase, directs the formation of a protein unique to
malarial parasites and is a potential therapeutic target. For example,
selective disruption of lipid synthesis in P. falciparum, would prevent the
organism from making new cell membranes, growing and reproducing in human
hosts.
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