Jul 4, 2010

SCIENCE NEWS - Pseudogenes are no more vestigial.

Pseudogenes, are defective copies of protein-encoding genes. Many pseudogenes can make RNA copies of the instructions contained within their DNA, but have flaws that prevent the next step in the process, making proteins. Because pseudogenes don’t make proteins, most biologists have thought of these genes as vestigial copies of functioning genes. But a new study, published in the June 24 Nature, shows that pseudogenes aren't dead yet, and may in fact be important regulators of their protein-producing twins. This discovery that pseudogenes may indeed have a function could transform biology, says Pier Paolo Pandolfi, a cancer geneticist and biologist at Beth Israel Deaconess Medical Center in Boston and Harvard Medical School who led the study.

In particular, Pandolfi’s group found that RNA from a pseudogene called PTENP1 acts as a decoy by drawing tiny regulatory molecules called microRNAs away from the pseudogene’s protein-producing counterpart, a powerful anticancer gene called PTEN. MicroRNAs are small pieces of RNA that bind messenger RNAs, also known as mRNAs. MicroRNA binding either causes the mRNA to be degraded or blocks protein production, effectively quashing activity of the gene. Many kinds of microRNAs can bind to the PTEN mRNA and reduce its ability to make protein. That could be disastrous, because cells are very sensitive to levels of PTEN protein. Lowering levels of the protein just 20 percent from normal is enough to cause precancerous changes in mice, the researchers previously discovered.

That’s where PTENP1 comes in. The pseudogene looks just like PTEN, except for a mutation that prevents it from making protein. Pandolfi reasoned that the microRNAs attracted to PTEN wouldn’t be able to tell the twin genes apart and that some microRNAs might go after the pseudogene, thereby protecting PTEN from too much attention. When researchers tested that idea by making more PTENP1 mRNA in cells, levels of PTEN protein increased, indicating that the pseudogene was acting as a sponge to mop up microRNAs that would otherwise reduce PTEN production. Removing PTENP1 from cells had the opposite effect — with nothing to distract the microRNAs, the regulatory molecules latched on to PTEN and squelched protein production.

The researchers also found that tumors from colon cancer patients were sometimes missing PTENP1, indicating that the pseudogene could help protect against tumors. A cancer-causing gene called KRAS also has a pseudogene, KRAS1P, that may be involved in stimulating tumor growth.

SCIENCE NEWS- How the leopard got its spots and the zebra its stripes!!!

British mathematician Alan Turing was one of the first scientists to explain how color patterns might form. Biologists are beginning to pinpoint the molecular mechanisms animals use to deck themselves out with colorful swirls, stripes, spots and dots.

A team led by Sean B. Carroll, a developmental and evolutionary biologist at the University of Wisconsin–Madison, recently found molecular evidence that preexisting patterns are important in directing color patterns to form. The researchers studied a species of fruit fly called Drosophila guttifera, which sports 16 black spots and four gray shadows on each wing. The black spots develop where wing veins cross, while the shadows form in the spaces between veins. Molecular detective work revealed that a protein called Wingless helps draw the spots. Wingless has many different jobs during fruit fly development, including properly orienting the fly’s body segments, directing where legs and wings will grow, and helping set up part of the digestive system. At some point in evolution, Carroll says, an ancestor of D. guttifera and some related fly species co-opted the Wingless system to create color patterns.

Still, the mechanism might also occur in other insects. Nijhout says that butter­flies, for instance, might use Wingless to create stripes on their wings, since the protein is made in the same places where bands of color later appear. A similar mechanism may paint the eyelike spots on some butterfly wings, using proteins called Distal-less and Notch instead of Wingless.

Animals such as fish, tigers and zebras don’t seem to position their spots and stripes over any particular body structures. And the pattern can be slightly different from one side of the animal to the other. Such clues suggest that pigment cells, which are born in one part of the body and migrate to their eventual location on the skin, assemble themselves into patterns according to a Turing-like mechanism.

David Parichy, a developmental and evolutionary biologist at the University of Washington in Seattle,
worked in zebrafish and supports the idea that multiple mechanisms are in play. He studies the way zebrafish form multicolored stripes along their bodies and on their fins. Along with colleague Jessica Turner, Parichy found that delaying the development of yellow pigment cells as fish transitioned from larvae to adults could cause their tail stripes to switch from horizontal to vertical. Some unknown factor, which the researchers are investigating now, must orient pigment cells in the right direction. And once pigment cells begin migrating, something has to tell them where to settle down. One protein Parichy’s group knows to be involved in making fish patterns is called basonuclin-2, which helps keep pigment cells healthy and allows the stripes to form. Fish that lack baso­nuclin-2 in their skin also lack stripes, the researchers reported last year in PLoS Genetics. “If the pigment cells are paints, the basonuclin-2 is essentially priming the canvas to receive these paints,” Parichy says. Until his team discovered basonuclin-2’s role in the skin, all of the other proteins known to affect stripe development were found in the pigment cells themselves. So fish may deploy a combination of pre­patterning along with a Turing-like mechanism to create their stripes, Parichy says.

Insects and fish are easier to work with in the lab than large cats like tigers or leopards, so scientists know much more about smaller creatures. For now, no genetic evidence indicates mammals might make patterns differently, or that leopard spots are fundamentally different from butterfly dots.

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