Quasispecies: A Wrinkle in Time

Super awesome review of viral quasispecies and what they mean, historically and currently:

Unfinished stories on viral quasispecies and Darwinian views of evolution.

They touch on so many good points, I could write about this review for a week! But just read it, cause I think you all can access it for free :P

One point I love: Quasispecies are like A Wrinkle in Time, connecting the origin of life to modern day viruses:

(on the origin of the quasispecies concept) First, there was the interaction between ideas from different fields of science such as physical chemistry and biological evolution. Second, there was the discovery that the concept of organizing genetic information in the form of quasispecies had relevance far beyond the idea of the origin of life. It was as though a time loop had joined microscopic and macroscopic knowledge together in our view of the world and established a link between the remote-in-time origin of life and current concepts about the genetic organization of RNA viruses.

Also, quasispecies give us a real-world framework by which we can test evolutionary/information theory concepts that were previously theoretical:

The addition of aspects arising from information theory complemented the theoretical framework. A multidimensional hypercube (cubes within cubes, as in a Russian nesting doll) served as a “space” for the theoretical representation of all the possible variants in a viral sequence. An important property of the space, referred to as a sequence space, is that all the variant sequences of a virus can be theoretically represented according to their kinship relation to the remaining variants. This framework served as a support for representing the fitness of each variant sequence in the sequence space (the fitness space) and for visualizing the correlation between fitness space and the distribution of the variants.

… Thus, several classic genetic principles applied to the evolution of the biological species, such as the Red Queen hypothesis, Muller Ratchet theory, and competitive exclusion, held up to experimentation and proved useful in viral quasispecies analysis. In contrast, experimental findings showed that the classic genetic concepts of wild type and mutant may not be applicable to molecular viral elements and that the idea of individuality does not relate to single, replicative RNA molecules but instead must be viewed in terms of a “clan” or quasispecies.

Theyve got a huge section on random mutation, fitness, and antiviral resistance, which several Creationists need to read.

And, a pretty funny commentary on the development of antivirals:

A drug reaches the last phases of development because it is predicted to have a reasonably good chance of being effective. Nonetheless, these predictions can fail when unexpected viral mutations that confer on the virus the ability to evade treatment develop. This outcome is so frequent that it raises the question of why scientists have been surprised again and again for decades by this “strange” phenomenon, instead of being surprised by the lack of flexibility of our concepts.

…There is enough experimental work to propose that at the RNA self-replication level, the “resistant” mutation is no more accidental than the “norm”.

…Despite the fact that the concept of quasispecies was initially developed as a deterministic theory, chance is an essential element in all of these theories, conferring plasticity on the systems described.

EXACTLY! This is a point I have really tried to drive home on ERV:

The moral of this story, children, is that HIV-1 does NOT need to ‘evolve’ resistance to all the drugs in HAART therapy. The drug resistance mutations are already there, in every patient, for no reason at all. Just chance. Its just a matter of how fit those resistant viruses are, and they do regain fitness over time. In some unfortunate patients, their quasispecies contains viruses that are resistant and very fit– you must change their drug regime immediately.

Random mutations, chance, are what a quasispecies is all about. The fact there are variants within a quasispecies that are resistant to any drug you happen to think up is 100% totally normal. Its not ‘miraculous’ or ‘proof of a Designer’ any more than water freezing at 32 F.

Thats just what quasispecies do. Thats just what water does. Its chemistry, not magic.

Fantastic review of quasispecies– You all should read it :)

Comments

  1. #1 Optimus Primate
    April 6, 2010

    Looks like it costs $31.50 to download and read. Unless I’m just missing something (which, on second thought, is entirely likely).

    Your summary is great, though. Thanks!

  2. #2 ERV
    April 6, 2010

    DANG IT!

    The PubMed page has a ‘Elsevier full text’ icon on it, so I thought everyone would be able to read it.

    DANG IT!

  3. #3 Michael Mathison
    April 6, 2010

    Since you’re a researcher studying evolution of HIV, I wonder if I could ask you about a study I read some years back. The NYT Science section carried an article on FIV in wild African cats. The key finding was that nearly the entire wild population of lions, cheetahs etc. carries FIV. The FIV virus rapidly kills T cells just as HIV does. However, the wild cats created new T cells just as fast as the virus destroyed them. As a result, the cats stayed healthy despite FIV infection. Are you familiar with this research? Doesn’t it suggest that the immunodeficiency viruses may have evolved first in cats, given that these cat species have evolved a defense mechanism for coping with the virus?

  4. #4 RIchard Jefferys
    April 6, 2010

    @Optimus Primate
    There’s an email address for the author, emailing and asking nicely for a PDF reprint often works.

    @Michael Mathison
    CD4 depletion has been documented in infected animals in the wild:
    http://www.jwildlifedis.org/cgi/content/full/42/2/234

  5. #5 Optimus Primate
    April 6, 2010

    Thanks for the tip, Richard! I’ll try that.

  6. #6 eddie
    April 7, 2010

    I thought we were all quasispecies. I mean, humans are not all clones. Nor are other animals, plants of bacteria. Something this obvious shouldn’t have such a wow factor.
    Having said that, the information theory modelling and hypothesis testing is great.

    Biodiversity seems to me to extend the concept to whole ecosystems.

  7. #7 nejishiki
    April 8, 2010

    #6
    Quasispecies theory, as first formulated by Eigen, assumes that there is a set of sequences with a positive rate of reproduction, among which there is a master sequence, which has the highest rate. The master sequence will remain as such as long as the error rate of reproduction stays below the Error Threshold. There are a few assumptions involved that don’t necessarily apply to larger organisms:
    -Comparatively few neutral mutations.
    -Several reasonably fit mutants around the master sequence.
    -The model is deterministic, holding for large populations.

  8. #8 eddie
    April 8, 2010

    Thanks for that, nejishiki. Although I’m not too happy with Eigen’s idea of a ‘master sequence’. Of the bullet points;
    - I think that’s why it’s better to think in terms of genes rather than organisms.
    - Isn’t the best sequence that which is most successful given the circumstances? Both are subject to unpredictable change.
    - Large populations are diverse and, even with the same diversity of aleles, may have different best sequences’ in different environments.
    Again, I’m not critiquing you but Eigen (as reported). Thanks for taking the time to respond. I’m off to read more on the guy.

  9. #9 eddie
    April 8, 2010

    Yeah. Who am I to critique Eigen. I’m merely an interested amateur who’s read others more qualified to do so. I had read of the ideas of Eigen, both the quasispecies on and his ideas on abiogenesis, but didn’t know the name until now.

  10. #10 Laura
    April 9, 2010

    I was going to be all, “heck, HIV relies on random replication errors to get from gag to pol!” Then I looked it up and discovered (contrary to what I was taught in 2nd-year microbiology) that there’d actually been an element directly facilitating this all along.

  11. #11 Antonio Mas
    July 20, 2011

    Thank you very much for your comments about our review!

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