Antibodies: Evolution in action II

Obviously, my first post on Antibodies: Evolution in action isnt the whole story, cause otherwise we would only have... like... eight different antibodies...


Thats obviously not the case.

Weve got lots and lots and lots of antibodies that recognize lots and lots and lots of different things!

Kevin has a post up at We Beasties on some of the initial stages of antibody development, V-(D)-J recombination!

Quick summary (GO READ HIS POST DONT READ JUST READ MY TWO SENTENCE SUMMARY!): A basic 'antibody' is composed of two heavy chains (blue) and two light chains (red) to make that 'Y' shape you think of when you think 'antibody'.
How those heavy chains and how those light chains are made requires the DNA of B-cells to be cut and pasted back together again. Im not going over that in much detail because Kevin did. But I will focus on one of Kevins figures.



There are lots of green squares and red squares and purple squares! WAT IZ DAT???

Why, its Evilutionists old friend, Gene Duplication!

There are a whole bunch of different 'V' portions of the heavy chain, a bunch of different 'D's and a bunch of different 'Js'. But the heavy chain of an antibody is only composed of one V and one D and one J! So you get lots of variations from all the combinations of V-(D)-J you can make! AND you have two of those V-D-J clusters-- One on the chromosome you got from Mom, and one on the chromosome you got from Dad, so theres even more diversity there!

The same happens with the 'V's and 'J's of the light chains, except you actually have two light chain loci in your chromosome to the heavy chains one, which means four different sets when you consider the chromosome you got from Mom + Dad.

If there was no way to 'add new information to the genome', as Creationists say, then you would really only have one antibody. But thanks to the new information added by gene duplication, you not only have antibodies with different butts (that would only get us up to eight antibodies), also thanks to gene duplication you have a GAZZILLION different antibodies because all those duplications can combine in different ways to make different antibodies!


See? Immunology doesnt have to be that scary! If you 'get' evilution, you 'get' more immunology than you might think!

More like this

That does it. The final disproof of Intelligent Design. For that matter, the final proof of Idiot Design: self-modifying code.

What this means is that on the elegant sophistication scale, animals are the biological peers of the PDP-8.

By D. C. Sessions (not verified) on 10 Aug 2011 #permalink

Damn. I'd hoped to avoid learning something today.

@4: Don't you love hyperbole?

Even granting the most ambitious claims, "nearly any" is "nearly any double-strand RNA virus." I can think of one or two exceptions.

By D. C. Sessions (not verified) on 11 Aug 2011 #permalink

Nasty science makes baby jesus cry!


Hyperbole? This drug has incredible potential. Being suspicious of a new magic bullet therapy will usually be the winning bet, but every once in a while something truly wonderful comes around. This may be one of those times you take your hat off, congratulate the inventors, and keep your fingers crossed. If in ten years this product revolutionizes human health you are going to wish you were more open to the possibility.

By Kevin Crawford (not verified) on 11 Aug 2011 #permalink

Hyperbole? This drug has incredible potential.

And indeed it may. But the press release "nearly any" claim is hyperbolic even if every actual result in the paper proves to be conservative.

Just to pick one, for instance, HIV is not a double-strand RNA virus. As Abbie might have point out if someone hadn't beat her to it.

By D. C. Sessions (not verified) on 11 Aug 2011 #permalink

D.C. Sessions,
I haven't gotten all the way through the paper yet, but they seem to be claiming effectiveness against so many viruses because, regardless of the structure of their genome, many viruses go through a dsRNA stage. The HIV protein TAT seems to be responsible for screwing with our dsRNA-detection system in order to protect HIV replication. So it seems HIV does have a dsRNA part to it's life cycle. Though I think there may be SOMEONE around here who knows a hell of a lot better.

Having said that, if I were you, and this turns out to be fairly damn wonderful in human clinical use 10 years from now, I would in no way feel silly for initial skepticism of a press release. In fact, I'm mostly in your corner with this, it seems to good to be true right now. I do hope it really is that good, but there may be all sorts of technical problems with actually implementing this, though the mouse studies they've done do make it more hopeful. Still this is one paper, from one lab.

Kevin Crawford: to put the "nearly any" in some perspective, here are a few viruses you may have heard of which aren't double-stranded RNA viruses:

Hepatitis B
Hepatitis C
Herpes viruses
West Nile virus
Dengue fever

Now I'm sure that there are quite a few double-stranded RNA viruses that I don't want to have partying in my bod, but most of the ones that scare me the worst are on that list above.

By D. C. Sessions (not verified) on 11 Aug 2011 #permalink

HIV-1 has no dsRNA stage in its life-cycle (I dont just mean structured ssRNA, I mean dsRNA).

RNA viruses must have a dsRNA step in their life-cycles-- its not technically 'dsRNA' the way we think of 'dsDNA', but RNA viruses must use a virally supplied RNA-RNA polymerase to make copies of their genome, and messenger RNA from their genomes for translation.

Thus this could work on any RNA virus, but not retroviruses.


Those viruses arenât defined as double-stranded RNA viruses because the infectious virion doesnât contain dsRNA. However, as Erk LR has noted, that doesnât mean dsRNA isnât generated during an infection.

The MIT researchers state DRACO is expected to work against HIV.

"But DRACO, they said, is also expected to zap measles and German measles, cold sores, rabies and even HIV -- and could be on pharmacy shelves in a decade, the Daily Mail reported. Lead researcher Mike Rider said: "It's certainly possible that there's some virus that we aren't able to treat but we havenât found it yet."

Iâm not sure the distinction erv is making between structured ssRNA (stem-loop HIV TAR sequence) and technical dsRNA is important.

By Kevin Crawford (not verified) on 11 Aug 2011 #permalink

Broad-Spectrum Antiviral Therapeutics

Todd H. Rider, Christina E. Zook, Tara L. Boettcher, Scott T. Wick, Jennifer S. Pancoast, Benjamin D. Zusman

Our DRACO approach combines two natural cellular processes. The first process involves dsRNA detection in the interferon pathway. Most viruses have double- or single-stranded RNA (ssRNA) genomes and produce long dsRNA helices during transcription and replication; the remainder of viruses have DNA genomes and typically produce long dsRNA via symmetrical transcription [4]â[5]. In contrast, uninfected mammalian cells generally do not produce long dsRNA (greater than ~21â23 base pairs) [4]â[5]. Natural cellular defenses exploit this difference in order to detect and to attempt to counter viral infections [6]â[7]. For example, protein kinase R (PKR) contains an N-terminal domain with two dsRNA binding motifs (dsRBM 1 and 2) and a C-terminal kinase domain [8]â[9]. Binding of multiple PKR proteins to dsRNA with a length of at least 30â50 base pairs [5] activates the PKRs via trans-autophosphorylation; activated PKR then phosphorylates eIF-2α, thereby inhibiting translation of viral (and cellular) proteins. Other examples of proteins that detect viral dsRNA include 2â²,5â²-oligoadenylate (2â5A) synthetases [10], RNase L (activated via dimerization by 2â5A produced by 2â5A synthetases in response to dsRNA [11]), TLR 3 [12], interferon-inducible ADAR1 [13], and RIG-I and Mda-5 [6]â[7].

By Kevin Crawford (not verified) on 11 Aug 2011 #permalink…

"Competing interests: THR is the inventor on patents and patent applications covering DRACOs: Rider TH (issued October 24, 2006) Anti-pathogen treatments. U.S. Patent 7,125,839; Rider TH (issued July 28, 2009) Anti-pathogen treatments. U.S. Patent 7,566,694; Rider TH (filed June 18, 2009) Anti-Pathogen Treatments. U.S. Patent Application 20100098680; Rider TH (filed February 7, 2003) Anti-Pathogen Treatments. European Patent Application 03716001.7; Rider TH (filed February 7, 2003) Anti-Pathogen Treatments. Canadian Patent Application 2,475,247; Rider TH (filed February 7, 2003) Anti-Pathogen Treatments. Patent Cooperation Treaty Serial No. US03/03978; Rider TH (filed February 7, 2003) Anti-Pathogen Treatments. Japanese Patent Application 2003565429; Rider TH (filed November 19, 2009) Anti-Pathogen Treatments. Japanese Patent Application 2009262426. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials."

By Richard Jefferys (not verified) on 11 Aug 2011 #permalink

Yes Richard, the author of that paper holds patents based off the work. What are you getting at?

Hey ERV,

Thanks for the post.

By any chance, could you write a post on RAG1/RAG2 and VDJ recombination and perhaps add some rants on the evolutionary roots of the immune system?



Kewl. Thanks for sharing. Again. :-)

Gonna take a lot of pot to understand all that.

Hey this, and it changes all of human history...

You read that, and you'll see you have a mathematical proof to gods existence, icbet my wife, my dick,and my house, read it:
it has some spelling errors but apparently the genius who wrote that wrote it on an iPad notepad.

By Sam flynn (not verified) on 29 Aug 2011 #permalink