Dear Kiki, Alan, Rich and Vincent,
Thank you very much for discussing our paper in the latest TWIV! It was great to hear your thoughts on the paper and the wider discussion of the quasispecies concept.
As we learned during the review process, there are a few issues that make the discussion of the concept so controversial.
From our viewpoint (and learning during the review process), the main bones of contention are:
1) “Traditionalists” in the evolution field have problems with one fundamental concept of the theory: that quasispecies theory predicts that the unit of selection is NOT the individual, but the entire population, the “ensemble” as Eigen calls it, that is the unit of selection.
2) The use of the term quasispecies by virologists is sometimes quite loose and it is, rightly so, criticized that it has been used synonymously with population diversity. A diverse population (of viruses) does not mean that they constitute a quasispecies.
3) The “killer” experiments are hard to do. In our view, one would need to start with a clonal (master sequence) virus, ideally with one virus genome that then diversifies and evolves. This is the exact problem because quasispecies, by definition and default, require large populations and because individual genomes, generally, have low fitness and require help from their colleagues. That is an experimental predicament that is hard to overcome.
4) Eigen, as you pointed out, developed the mathematical model (I like your bonmot on models, Rich!) originally for macromolecules, but subsequently extended it, mainly with Peter Schuster, to the situation in RNA viruses. While Esteban Domingo, Raul Andino, Marco Vignuzzi and others have accumulated abundant evidence in support of the theory, we come back to (3) and have to admit that definitive proof is hard to come by.
The good news is that it will keep the community busy for years to come 🙂
Jakob and Klaus
PS: maybe this is of interest: https://naturemicrobiologycommunity.nature.com/users/292496-nikolaus-osterrieder/posts/52973-varietas-delectat-how-teetering-on-the-verge-of-extinction-can-benefit-virus-evolution
Institut für Virologie
Robert von Ostertag-Haus –
Zentrum fuer Infektionsmedizin
Robert von Ostertag-Str. 7-13
Dear TWiV Team,
Here are my unsolicited off-the-cuff five cents on the term “quasispecies” in virology.
One can interpret the term in 4 different ways:
“Quasispecies” as a synonym for “virus population” or “population of virus clones”. If seen as a such a synonym, then the term “quasispecies” is basically useless as you will have to explain the term “quasispecies” to a larger audience than you would have to explain the term “virus population”. Since a big part of science is the communication of scientific results and their interpretations, novel or complicated terms should not be used when simpler and more broadly comprehensible terms are available that have the same meaning. Just like using “pyrexia” instead of “fever” or “epistaxis” instead of “nose bleeds” may be interpreted as elitism or even otherization (making an in-group special by keeping other people out of a conversation), “quasispecies” would fit that bill.
“Quasispecies” as a literal connection of the words “quasi” and “[biological] species”. Since there is no consensus among biologists what a “species” is and since “quasi” means “apparently but not really or almost”, the term would then amount to “apparently but not really being something that we haven’t defined”. In short, the term “quasispecies” would be utterly useless scientifically.
“Quasispecies” as a literal connection of the words “quasi” and “virus species”. As discussed in previous TWiV episodes, in virology, a virus species is interpreted as a category or human concept, i.e. not a tangible thing that one can touch or study. Species are established, and viruses, which are things, are assigned to species. A “quasispecies” would therefore “apparently but not really be a category”, and that doesn’t make much sense except if there “is” something between things and not-things that I am not aware of. Aristotle could help, probably
“Quasispecies” the way Manfred Eigen, the Nobel Laureate who coined the term, defined it. You repeated that definition a few times on the show, but I think you focused on the wrong thing and left out the important part. It is true that Eigen coined the term for macromolecules and not specifically for viruses. However, the point he made was that a quasispecies is a group of related but not identical molecules that together behave as one, rather than as individuals. This concept can very easily be applied to virology: imagine a population of 5 infectious (+-sense RNA) virus genomes that are 99.9% identical in sequence. Assume 4 of the 5 have distinct lethal mutations somewhere.
Now imagine injecting all five virus genomes together into a susceptible animal. You just worked with a “virus population”. If it is just a “virus population”, but not a quasispecies in the Eigen sense, then you get an infection because the 1 genome without a lethal mutation will for sure replicate and outcompete the 4 other ones that either do not replicate at all or only replicate with the “help” of the functional virus (one-sided dependency “exploiting” a functional protein of the complete virus). The result of replication is a new virus population either only derived from the functional virus or derived from the functional virus and the dysfunctional viruses that were replicated by the functional virus
Now imagine injecting each virus individually into susceptible animals. If there is no quasispecies in the Eigen sense, then 4 viruses would not lead to infections because they cannot replicate by themselves and 1 virus would replicate because only that one is functional. This 1 virus would create a new “virus population” in the non-Eigen sense. However, if the 5 viruses are a quasispecies in the Eigen sense, then none of the 5 viruses would create an infection individually, because they all need each other, and you would have to inject all 5 viruses together. In this case, the defective genomes would be able to replicate because the one functional virus would function as a helper, but in return the functional virus would gain a crucial survival benefit through the replication of the defective viruses. In this scenario, the 1 virus would not “take over” and outcompete the other 4 viruses, but instead the 5 viruses would evolve with each other (“as one”) and compete against other groups of interdependent viruses. Any detrimental event on any one of the five would kill all remaining four viruses.
While such Eigen scenarios are difficult to prove in virology, I feel the interesting and completely understudied dynamics of defective-interfering (DI) genomes and DI particles point towards the likely existence of Eigen’s quasispecies in virology (and the equally interesting dynamics of satellite viruses and satellite RNA represent similar systems of evolutionary interdependence although here the underlying genomes are highly distinct rather than highly similar).
An example: one can imagine that a virus has evolved to produce certain DI particles (particles containing mutated genomes that are almost identical to the parent virus genome) that, say, have a different tissue tropism than the main particle (through, say, a single point mutation in the envelope protein). These DI particles could take out key immune cells by entering them even though those DI particles do not multiply in them; whereas the main particle could not enter these cells. This would then allow the main particle to go unhindered into its target cell, which the DI particles cannot enter. If the main genome mutated and therefore does not make these particular DIs anymore, then it would go extinct because the immune system would not be suppressed by the DI particles. Voila: interdependence of highly related virus genomes and an Eigen quasispecies [quite a bit oversimplified, but I think it’s clear enough].
In short: until it is proven that in virology Eigen quasispecies do NOT exist, one shouldn’t appropriate the term for something else. And if it is proven that Eigen quasispecies do NOT exist in virology, then there is no need anymore for the term “quasispecies” as “virus population” is so much clearer
Jens H. Kuhn, MD, PhD, PhD, MS
Battelle Memorial Institute – Contractor supporting:
National Institute of Allergy and Infectious Diseases (NIH/NIAID)
Division of Clinical Research (DCR)
Integrated Research Facility at Fort Detrick (IRF-Frederick)
Weather report: Pretty nice here in northern NJ, except for some humidity and scattered cases of a virus that the media is working hard to sensationalize. Any chance you guys can cover eastern equine encephalitis virus in an upcoming episode?
Many thanks from a recovering neuroscientist (crossed over to the dark side, pharma consulting, after getting my PhD)
While I am not in the habit of recommending my own papers for discussion on TWIV – there is a first time for everything! When you were at Einstein recently to speak to our Graduate Viruses class, I had a chance to give you an elevator pitch of our manuscript that was in review. That manuscript is now a published report in eLIFE. The reasons why I think it would be worth discussing on TWIV are the following.
- There are no known extrinsic factors that modulate cellular ESCRT or associated factors in a way that controls the budding/release/replication efficiency of any virus.
- Beta chemokines like CCL2, are considered inflammatory chemokines, secreted upon the infection of macrophages in order to deal with the infection – but we show that HIV utilizes CCL2 for enhancing its replication further.
- We show a curious finding that while most HIV isolates have two different late domains – subtype C HIV-1 which dominates half of the world, entirely lacks the second late domain possibly as a means to keep its replication to a minimum. By being a less fit virus, it seems to be able to spread more efficiently and get it to more people. We also show that, subtype C HIV-1 reacquires a different type of second late domain in some patients, where it replicates better.
- Lots of RNA and DNA viruses possess the same exact late domain and also induce CCL2 upon infection of cells – thus the same exact mechanism is likely to be operating in a much wider group of viruses.
Here is the link to the paper!
P.S.: Just to restate: I am known as Prasad among friends and close colleagues – not Vinny or Vinayaka.
Vinayaka R. Prasad, Ph. D.
Professor, Department of Microbiology and Immunology
Albert Einstein College of Medicine
Today’s TWIV (566) was on point to my TWIP note this afternoon about excessive air travel.
Peripatetic’s Greek root is “walking up and down”. I’d be cool with more journeys by foot, EV or train.
Bill Spindler writes:
The one in Ithaca, the Sagan Planet Walk, is downtown, with the Sun on the Commons and the various planets strung out northward. I’ve seen it more than once, most recently in 2011 when there for my 40th reunion, but from the current website it’s been revised significantly since then, with different planet models. The main link is here http://www.sciencenter.org/sagan-walk.html but also of interest is the Wikipedia article which describes its history https://en.wikipedia.org/wiki/Sagan_Planet_Walk …note that it was first built in 1997, and that it was significantly expanded in 2012 with an obelisk at the University of Hawaii at Hilo, thus making it the world’s largest exhibit.
Two others I’ve seen more recently are in Anchorage, where the Sun is in the middle of downtown with the planets laid out to the west through downtown and along the Tony Knowles Coastal Trail, and a much smaller scale at the center of the University of Colorado Boulder (about a mile SW of me).
BTW, Kathy I got caught up on TWIV today!
Bill Spindler’s Antarctica
TWiV 562 – on the failure to see the big picture
“Over the years, I have lamented the disappearance of both thought and experiment from biology and the rise of ‘e-biology’. “
# # #
In TWiV 562, I believe you mentioned the problem of researchers failing to see the big picture. I won’t claim to see the picture myself, but I will mention that I’ve wondered about a lack of perspective. And what’s worse is that the vast technological resources now available can be mistakenly relied on as a replacement for critical thinking.
Darwin’s first reflection on the age of the Earth and the accumulation of effects through time wasn’t from Geology as high school Biology texts teach. Darwin noted that we know that the Romance languages came from Latin over the course of 2000 years or so. He then reasonably assumed that Hebrew and Greek both came from some common source. His conclusion was that this could not have taken place over just 3000 years. Darwin’s grounding in the Liberal Arts trained him in the critical thinking that enabled him to formulate the Theory of Evolution.
Hi Vincent & TWiV crew,
Interesting story on different tactics to fight anti-vaxx. Maybe you could get one or both of the two vaccine activists featured here on TWiV sometime? You’d also get to practice your Italian 😉
This comes as vaccine laws escalate all over the united states in various political debates in various states over how to reduce vaccine exemptions. As a resident of California I am seeing Richard Pan get politically attacked over Vaccine laws in California and other states are debating to see if they should use SB276 and SB277 for their vaccine laws.
Do our current elected officials understand that the United States will Lose their measles eradication status soon?
This comes as various states are fighting to debate over having vaccine laws similar to California and Richard Pan (Member of the state Senate in California) is getting national attention for being politically attacked by Anti-Vaxx Members.
Dear Queens and Kings of the Virology Kingdom,
Greetings from Toronto (where it is +16 C late night, but was 19 C during the day, ideal for playing tennis outdoors)!
This year is the 150th anniversary of the Periodic Table, so all the links below are related to the periodic table:
1) The Royal Society of Chemistry (RSC) has a series of podcasts on chemical elements. Here is the link to their audio podcasts: https://www.rsc.org/periodic-table/podcast
2) Here is the link to RSC-based video podcasts on chemical elements, some compounds and other chemistry-related videos. These video podcasts have been created by Prof. Martyn Poliakoff and his colleagues from the University of Nottingham (UK): http://www.periodicvideos.com/
3) I have selected a few episodes to give some exciting examples. This episode is about Vanadium, and it contains a very cool demonstration: http://www.periodicvideos.com/videos/023.htm
4) Having recently visited Sweden, Vincent may enjoy this Sweden-related episode about Ytterbium: http://www.periodicvideos.com/videos/070.htm
5) Since Alan has a special interest in aviation, he may enjoy this episode about Rhenium: http://www.periodicvideos.com/videos/075.htm
6) If someone (for example, grant reviewers) starts questioning your proposal because they think it has no practical use, you can show them this episode about synthesizing “superheavy” elements, which will highly unlikely have any practical applications, except being very useful for understanding fundamental principles of atomic structure and comparative chemical properties of various elements. This episode is on the YouTube channel of the Periodic Videos project: https://www.youtube.com/watch?v=z3oY-XHwss8
7) Another very interesting episode about a nuclear reactor used for producing rare isotopes used for the synthesis of “superheavy” elements: https://www.youtube.com/watch?v=P99C051arMo&t=636s
Keep up your great work on virology education!
All the best,