Latent evolutionary potential and quasispecies

Gawd I love doing HIV-1 research. Stuff that takes big-stuff-biologists millions of years to watch, we can figure out in a few weeks. Case in point: PZs post yesterday on 'latent evolutionary potential'.

Ah, the realization of latent evolutionary potential. Did you know that you have latent evolutionary potential? Sure. If we put you and your family and friends in a novel environment, and let the generations tick by, we'll discover that certain sets of traits will become more prominent as selection and drift take their toll. The phrase does not imply that there is a purposeful arrangement of genes in your body that are there with a preexisting intent to allow you to thrive in a particular situation. You are complex, you have many properties that may in your current situation be superfluous or useless, but could be utilized in different situations.

Heck yeah! We have to deal with 'latent evolutionary potential' all the time when we are dealing with HIV-1, because HIV-1 behaves as a quasispecies-- a HUGE, dynamic population of viruses, where each virus is totally unique, yet they are all still related to one another. Its just genetic drift to the extreme. hehe!

So you cant look at any one HIV-1 sequence and say "this sequence is the way it is because of some evolutionary advantage". It might just be the way it is because HIV-1 mutates a lot, but that particular sequence is still functionally viable. Individual sequences dont really mean anything. You have to look at the population as a whole. Because the way HIV-1 drifts... its going to screw us over, bad, if we dont figure out a vaccine soon:
Minority Quasispecies of Drug-Resistant HIV-1 That Lead to Early Therapy Failure in Treatment-Naive and -Adherent Patients

The invention of antiviral therapy for HIV-1 infection has led to an obvious clinical problem: drug resistance. When we only had one/a few anti-HIV drugs, this was a BIG deal, but now that we have a whole cadre of drugs, each a little bit different than the others, not only can we pound HIV-1 in patients with several drugs at once (HAART), but if the virus evolves resistance to one of the components of a patients cocktail, you can switch it out for a different one. We have options now. YAY! Keeps patients viral loads low, keeps transmission potential low, keeps people alive. Again, YAY!

An increasing problem is when newly infected HIV-1 patients already have viruses with major antiretroviral resistance mutations. So these patients get a usual cocktail... and shit... their viral load doesnt go down.

So recently, physicians started screening patients at the time of diagnosis for these resistance mutations, so they know not to even bother with Drug X/Y/Z.

Now weve got a new problem. Patients are getting screened for resistance mutations, coming up negative, and their cocktails still arent working. Double shit. Its not because they arent taking their drugs at the right time (sometimes non-compliance leads to no decrease in viral load), their bodies are processing the drugs properly (you can check blood levels for active concentrations), the drugs just arent working.

What the hell.

Well the test to look for drug resistant mutations can only find the resistant variants if they make up ~20% of the total HIV-1 quasispecies.

Metzner et al used a different test for resistant mutants-- a super, super, sensitive one, on the patients they had that were negative on the usual test, but didnt respond to drugs.

Turns out that the resistant mutants were only present in the patients quasispecies at ~0.07%-2.0% at the time of diagnosis. The second patients were given antiretrovirals, >98% of the viruses were killed, but that <2% of viruses that were resistant had the opportunity to thrive, to the point where at 5 weeks after one patient was given drugs, 99.3% of the viruses in his system had a particular resistance mutation (and remember, his viral load was still high).

Each resistance mutation (they looked at several) was present at different levels in the quasispecies post-drugs in each patient (four patients in this study), but they all followed the same pattern: Pre-drugs, just a few resistant viruses. Post-drugs, a huge viral load, and ~99% of them have a particular resistance mutation.

What happened in these patients is exactly what PZ was talking about yesterday. The HIV-1 quasispecies isnt 'front loaded' by an 'intelligent designer' to be resistant to drugs. HIV-1 isnt consciously anticipating needing to avoid antiretrovirals. There is just a lot of drift with HIV-1, so some sequences that pop up by chance just dont 'mean' anything. Its just drift. Until there is a change in the environment, like the presence of antiretrovirals, where those 'meh' mutations turn into 'the only genetic variants that can survive'.

So Ill repeat that quote from PZ again:

Ah, the realization of latent evolutionary potential. Did you know that you have latent evolutionary potential? Sure. If we put you and your family and friends in a novel environment, and let the generations tick by, we'll discover that certain sets of traits will become more prominent as selection and drift take their toll. The phrase does not imply that there is a purposeful arrangement of genes in your body that are there with a preexisting intent to allow you to thrive in a particular situation. You are complex, you have many properties that may in your current situation be superfluous or useless, but could be utilized in different situations.

No Jesus required.