Monday, September 3, 2007

Wolbachia cronenbergium


My, the folks over at the Venter Institute have been busy lately. First they changed one microbe species into another by physically replacing its entire genome. They did this in their quest to create a synthetic organism, basically a chassis with the absolute minimum number of genes necessary for life, which could then be loaded up with other customized genes designed to act for the betterment of humanity and the environment the good of Venter stockholders. Now they've discovered that Nature herself has done them one better, by incorporating the complete genome of a parasitic bacterium called Wolbachia into the code of fruit flies: two complete genotypes for the price of one (original article here: much more accessible press release over here).

Some of you may remember ßehemoth, from the rifters books: it was basically mitochondrion's nasty cousin, and like mitochondria it brought its own genome into the host cell. This is a big step further: Wolbachia's code isn't just hanging out in the cell, it's been incorporated into the nuclear DNA of the host itself. The host is not infected with Wolbachia; there are no bacteria cruising the cytoplasm. Rather, the complete recipe for building the bug has been spliced into the host's code— and since the odds of such a big chunk of data (over a megabyte) getting thus incorporated without playing any functional role are pretty small, chances are that this embedded genotype is doing something for the host organism. This is assimilation: the dicks of Borg drones everywhere should be shriveling with collective performance anxiety.

Two major implications come immediately to mind. The first is that conventionally-derived genotypes sequenced to date might be all washed up, since bacterial DNA is routinely scrubbed from such results as "contamination"; but if this new phenomenon is widespread (and Wolbachia is one of the world's most abundant parasites of invertebrates), a lot of the bathwater we've been throwing out might actually be the baby. And the second implication, well —

Anyone remember David Cronenberg's remake of "The Fly"...?

(Illo credit, as far as I can tell, goes to the University of Rochester.)

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16 Comments:

Anonymous Anonymous said...

This comment has been removed by the author.

September 4, 2007 at 11:15 PM  
Anonymous Anonymous said...

A History of Violence was several orders of magnitude better than 'Dead Ringers'. That movie was so bad I almost wept.

He is permanently forgiven for eXistenZ though.

I wonder how Naked Lunch was. I can't believe someone tried to make a movie out of it. Any chapter would pretty much make the most bizarre movie ever needing to be made.

PS I know nothing about biology. I did play WoW for a while though.. ;)

September 5, 2007 at 1:05 AM  
Blogger tobias said...

having seen these reports in the press reccently (but having been too lazy to read the appropriate articles) i have to say as a virologist, big deal!!!!
retro and lentiviruses genome intergration has long been know off. Though their genomes are significantly smaller so i presume they wont have such a significant effect on the host cell.
whats the percentage of the human genome thats being alledged to be historically intergrated viral genomes?

September 5, 2007 at 8:52 AM  
Blogger Legba said...

It probably does mean that they will get to resequence a lot of organisms to check for inclusions of this kind if they weren't careful and kept their raw data after publishing. My biology isn't that hot but does this mean that fruit flies use Wolbachia enzymes for their own use? Shamelessly ripping the intellectual property the Wolbachia worked so hard to make :P

And when the first synthetic organism is unveiled it will be so much fun to see the bible guys saying it is unnatural and hellspawn and the media spelling doom with predictions of synthetic diseases. I believe it will be far from easy to make something that is even slightly resistant to predation and infection, let alone something that can beat bacteria that have evolved for thousands of years to infect humans.

September 5, 2007 at 8:54 AM  
Blogger HannuB said...

Well, I might be just another fanboy who hasn't got a clue, But I don't think I've ever seen a bad Cronenberg movie. I've seen them all and liked them all, even the supposedly bad ones. Videodrome's still my absolute favorite. "Long live the new flesh!" Oh, it was sublime...

I've always wondered what kinda movie Cronenberg would make out of Starfish. With Jennifer Jason Leigh as Lenie Clarke and Rutger Hauer as Ken Lubin, maybe? Just a thought...

Oh, and I know nothing about biology either. But it's all WoW's fault...

-Hannu

September 5, 2007 at 9:16 AM  
Blogger Peter Watts said...

Scott C. said...

You see what happened here, right? You went and dumbed up the joint with the "World of Warcraft" references and slumming with the Xfire crowd. Now nobody knows what to say when you start smartificating.

'Twas ever thus, I think. I post some piece on self-replicating carbon helices and nary a twitter. I weigh in with another installment of All Humans Are Assholes and the comments fly like shit in the Senate.

If I wanted this blog to really take off I should just make it All Misanthropy All the Time. Although I might have to wait until Harlan Ellison died, to avoid being sued for trademark infringement...


robf wondered...

...how Naked Lunch was. I can't believe someone tried to make a movie out of it. Any chapter would pretty much make the most bizarre movie ever needing to be made.

Personally, I though Naked Lunch was great. Cronenberg didn't film the book so much as he filmed Burroughs's headspace while he was writing the book — which, given the synapse-fried state of that brain, was every bit as weird, right down to the mugwumps.

Be warned, though: I didn't think Dead Ringers was half-bad either.


tobias grumbled...

... i have to say as a virologist, big deal!!!! retro and lentiviruses genome intergration has long been know off.


Well, sure, LGT is old news. But a whole genome nested inside another? Doesn't that take things to a new level?

Granted, if you read the actual paper they didn't test exhaustively for the whole genome, just for representative genes sprinkled along its length. But whole-genome incorporation is way more likely than all those separate fragments just happening to get incorporated independently. And they don't seem to know what adaptive function, if any, this new bolus of code actually confers to the host. They just consider it unlikely that such a big add-on would be neutrally adaptive, and if it were deleterious it would've been weeded out already, which leaves...


Legba said...

And when the first synthetic organism is unveiled it will be so much fun to see the bible guys saying it is unnatural and hellspawn...

Oh, I don't know. If the first synthetic organism was intelligently designed to provoke episodes of religious mania, accompanied by instinctive largesse to honey-tongued orators with smarmy smiles and helmet-hair, the biblethumpers might decide it wasn't half-bad...

September 5, 2007 at 9:31 AM  
Blogger TheBrummell said...

Dr. Watts, In the post: ...and since the odds of such a big chunk of data (over a megabyte) getting thus incorporated without playing any functional role are pretty small, chances are that this embedded genotype is doing something for the host organism.

Dr. Watts, In a comment: And they don't seem to know what adaptive function, if any, this new bolus of code actually confers to the host. They just consider it unlikely that such a big add-on would be neutrally adaptive, and if it were deleterious it would've been weeded out already, which leaves...

I haven't yet read that paper - I'll put it on my list for this week. BUT, "selective advantage" should NEVER be the default explanation, the null hypothesis. 1 MB of some compact bacterial genome plugged into Drosophila's 180 MB doesn't automatically scream "advantage" to me. Is it being transcribed? Translated? Is the difference in codon bias (among other things) screwing with expression profiles?

Neutrality is the prefered null hypothesis, in this as in so many cases. Raw genome size varies over five orders of magnitude in animals, more across all eukartyotes, but the total number of coding genes probably only varies by a factor of 10 or so. Are you going to try to convince me that every last MB of every genome is adaptative?

Tobias: whats the percentage of the human genome thats being alledged to be historically intergrated viral genomes?

I seem to remember estimates around 40% SINEs and LINEs, both of which are thought to be ancient viral genomes that proliferated post-insertion. For comparison, current estimates for coding DNA (i.e. "genes" plus regulatory sequences like promoters) run around 2 - 5%. Yes, you're just a big bag of virus, like that hypochondriac/obsessive-compulsive down the street always said.

September 5, 2007 at 2:09 PM  
Blogger AR said...

I believe it will be far from easy to make something that is even slightly resistant to predation and infection, let alone something that can beat bacteria that have evolved for thousands of years to infect humans.

That depends on how far off the standards the designers go. If what they create is sufficiently alien, parasites and predators might not know what to do with it. Just look at how harmful species from other continents can be to local ecosystems.

On the other hand, the human immune system is designed to handle so many different sorts of invaders on the fly that any synthetic invader will probably still get caught by a few of the several systems we have for dealing with that sort of thing, unless a plague was the design goal to begin with.

At the same time, the evolutionary history of most infectious agents is to our advantage. Many of the things that kill humans did not evolve with "parasite of humans" as their niche, like Clostridium botulinum. Good parasites don't kill their hosts. For every organism that kills people, there are hundreds of organisms that cause a cold, spread, and get exorcised from our systems without too much trouble. It's a compromise. In fact, HIV is observed evolving into less lethal strains as we speak. The longer you live asymptomatically, the more you will spread the virus, thus slower acting strains have an advantage. The problem with a synthetic organism could be that it would not have nearly so much concern for out well-being and end up lethal.

On the other hand, such an organism is also very unlikely to be able to spread easily for the exact same reasons and may well just burn out after killing its initial hosts too quickly.

September 5, 2007 at 4:20 PM  
Blogger Peter Watts said...

TheBrumster, wisely cautioned...

"selective advantage" should NEVER be the default explanation, the null hypothesis. 1 MB of some compact bacterial genome plugged into Drosophila's 180 MB doesn't automatically scream "advantage" to me. Is it being transcribed? Translated? Is the difference in codon bias (among other things) screwing with expression profiles?

Neutrality is the prefered null hypothesis, in this as in so many cases. Raw genome size varies over five orders of magnitude in animals, more across all eukartyotes, but the total number of coding genes probably only varies by a factor of 10 or so. Are you going to try to convince me that every last MB of every genome is adaptative?


I have to admit I kind of blinked at the "not-likely-to-be-neutral" bit myself, given that so much of everything's DNA is noncoding (even after taking into account all those subversive late-breaking little RNAs). But given how little I know about this stuff, I just assumed I'd missed another paradigm shift. I mean, the paper's peer-reviewed and everything...

September 6, 2007 at 1:42 PM  
Blogger TheBrummell said...

...the paper's peer-reviewed and everything...

Yup, and we both know approximately how much that counts for in the grand scheme of things.

This paper also won an award!

http://phylogenomics.blogspot.com/2007/08/adaptationomics-award-1-wolbachia-dna.html

Still, the rest of the science in that paper is really cool and looks solid to me. I guess I shouldn't be surprised that a discussion section contains some wild speculation, lots of other papers I read do that, too.

September 6, 2007 at 3:06 PM  
Blogger tobias said...

most of my scientific career to date could be filed under "wild speculation"

September 7, 2007 at 4:52 AM  
Anonymous Anonymous said...

Well, I have one of those Blockbuster "send me movies while I sit on my ever-fattening ass" things, so I will try Naked Lunch.

However I am suspicious, Dead Ringers was sobad. It was like.. a racy 80s soap opera or something. Jeremy Irons is a good actor too.

September 8, 2007 at 2:11 AM  
Anonymous Anonymous said...

Merely inserting its own genome into another organism is nothing. According to Patrick Forterre's theory, the 3 domains of life (Bacteria, Archaea, and Eukarya) each formed from RNA-only ancestor cells when 3 (lucky?) viruses inserted the entire machinery for handling DNA and then failed to kill their hosts. Now that is evolutionary success.

January 15, 2008 at 10:46 AM  
Blogger Lorenzo Pacheco said...

Some of your nomenclature is a bit off.

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