Tuesday, April 28, 2009

"Junk" Genes Fight HIV ?

It's a bit of a departure for this blog, but a fascinating bit of news has surfaced recently:
"Junk DNA" are inactive parts of your genome, switched off long ago in evolutionary history. Now scientists say there's a junk gene that fights HIV. And they've discovered how to turn it back on. [via io9.com]

All the gory details can be had in an article from PLoS Biology. Perhaps our beloved resident geek girl IT can comment...


IT said...

I shall read the paper on the train this evening and post my comments tonight. :-)

dr.primrose said...

OT (as usual). According to Episcopal News Service, the court in upper New York state has smacked down Matt Kennedy again for the screwing around with the property as he walked out the door -- Departing parishioners not entitled to bequest.

The story says in part:


In his earlier ruling, [Judge] Lebous had required the departing members to provide an accounting of the status of parish property. The diocese told the justice that some known property, including stock shares, was not produced. The justice found that no income had been flowing into the parish since April 2008.

Lebous found that "the parish was doing everything it could to spend down the assets, divert new income, and perhaps actively interfere with the diocese's right of ownership." He ruled that the diocese "has every right to conduct an investigation into the income and property of Good Shepherd."

The justice told the treasurer of the breakaway congregation and the Rev. Matthew Kennedy, the rector, that the investigation would begin with them being questioned within 45 days about what they had done with other church property.


Lebous had been asked to rule on the ownership of a gift that a former clerk of the Good Shepherd vestry, Robert Branan, made in his will. He left $1,500 "together with all my diamond, ruby and opal rings for the purpose of creating a chalice and paten." The jewels were to be set into the vessels.

In addition, 25% of Branan's remaining estate went to a parish memorial fund. Branan put the remaining 75 percent in a trust for two women and provided that the proceeds of the trust to go to the parish upon the death of both.

Branan also specified in his will that if Good Shepherd parish ceases to exist or merges with another parish the entire bequest would go to Christ Church, the oldest Episcopal Church in Binghamton.

Good Shepherd told Lebous that Good Shepherd still exists even though the majority of its members and leadership have disaffiliated with the Episcopal Church.

"While Good Shepherd may have abandoned the Episcopal faith, Mr. Branan never did, and his intent was clearly to benefit a local Episcopal church," the justice wrote. He added that there is "simply no basis on which to find that Mr. Branan would want his money to go to those former members of the Church of the Good Shepherd that abandoned the faith that he, apparently, held so dear."

IT said...

That is so sad.

IT said...

Back on topic, I read the paper. It's an interesting idea.

Basically, in a process called innate immunity, our bodies produce small proteins (peptides) that antagonize a variety of different infectious agents. This doesn't rely on our complex and elegant immune system but is a very primative mechanism of protection. Similar examples of innate immunity are seen all the way down the phyla to fruitflies and fishes.

One such molecule, the theta-defensin, is actively produced in old world monkeys and helps prevent HIV infection by blocking the virus from entering cells. But in humans, the cognate gene has a mistake in it, which prevents our cells from translating the genetic information into a protein. Basically there is an erroneous "STOP!" signal in the middle of the gene.

These authors have two major findings. First, they used molecular biology to fix the mistake in cells in culture, and asked whether human cells that were now able to express the theta-defensin peptide were more resistant to HIV. They were.

Second, they wondered if it would be possible to induce cells to ignore the STOP signal in the regular human theta-defensin, perhaps by making the translation machinery less efficient and more prone to ignore STOP signs. (Like a teenage driver doing a California roll at 20% of stop signs). This "read through" where the machinery ignores some stop signs would allow cells to make some theta-defensin. The did this using an amino-glycoside antibiotic, which effectively makes the cells less efficient at recognizing STOP signs. It worked. And, they had a small, but discernable effect on the resistance of cells to HIV.

Now, the BIG problem with this that I see is that if the aminoglycoside can induce readthrough of this gene, it can also cause genes with perfectly normal "STOP" codons to ignore the proper punctuation and keep reading, thus making aberrant products. There could be unanticipated and deleterious effects by preventing "good" genes from stopping translation when they should. A "good" STOP looks just like a "bad" STOP so there is no way of telling the system to distinguish one from the other. So it's cute, but maybe not so therapeutic. On the other hand, a microbicide with theta-defensin might be helpful.

(Aside: they coin the name retrocyclin for theta-defensin. This is a really REALLY bad name; there are already two other uses for the word "cyclin" , and the most accepted one has nothing to do with innate immunity. THese are WELL established in the literature and thus "retrocyclin" is really NOT appropriate. Retrocyclic maybe.... rant off.)

Our genomes are loaded with forgotten genes, the remnants of long-lost viruses that got "stuck" by mutation, or pseudogenes like these that once were expressed and then got turned off. With all the genomes that have been sequenced, we have a much better idea of the enormous amount of variation between people, and the fascinating archeology of lost genes in the species.

David |Dah • veed| said...

I think that we got AMBUSHed!

IT said...

Yeah, I think that we can eliminate that....I wonder where these trolls come from...notice they only come out in the dark....

NancyP said...

I agree, IT, I would favor something like "retrodonut", or "retrotorus" for the pompous-minded, since the name indicates a shape, not a role in the cell cycle.

P.S. Supposing the little circular peptide turns out to be glycosylated - would it be a "retroglazeddonut"?

(IT grabs hook, hauls NP off stage)

By the way, IT, you are right concerning aminoglycoside problems - we eukaryotes are relatively resistant, but still the aminoglycoside group of antibiotics gives us serious side effects, most prominently to hearing (kills cochlear cells) and kidney.

IT said...

Kills cochlears? How odd. Is it due to translational effects or something else?

IT said...

BTW NancyP, BP just read your comment about Retroglazeddonut and about fell off her chair. She appreciates good molecular biology humor.