Goykhman: After i did my botulinum presentation, the professor asked me to speculate about the function of the toxin. I had a light bulb go off in my head I think your right, its a total accident. Because....
1) evolution must favor survival of bacteria whose has a protein that just exogenously just sticks to a neuron. this wont favor survival and therefor cant be selected for
2) then favor endocytosis?....nope, it will not be selected for
3) Pore formation? dont think so this wont favor survival
4)translocation ...(see above)
5) Substrate cleavage....ok, this might help it kill an animal, but the first 4 steps confer no advantage for selection.....SOOOO...the only way to get the BoNT toxicity is by accident.Anyway, now that I know what you were trying to say. It kinda makes me less interested realizing BoNT is not some amazing nanomachine.., or the engima it was yesterday..., but a total fluke.
i'll to bromage so he gets it.....
Goykhman: i mean not only to validate your point..its dissappointing knowledge...and I gotta bring everyone down with me down with me
Alex: The biochemical function of BoNT (Botulinum NeuroToxin) is clear known and there is no need to speculate it. BoNT is an endopeptidase for sure, that is all. The problem is how does BoNT evolve the ultra high specificity (where the high toxicity comes from) to recognize the substrates and thus block the exocytosis. BoNT is not the only Zn-dependent protease in the world. Its action mechanism of endopeptidase is similar to most of known Zn-dependent protease in organic chemistry reaction. The original function of BoNT is simple and must be used for the digestion of food, just like other protease. The phenotype of BoNT in vertebrates becomes neurotoxic is completely an accident during the evolution. BoNT gene did not set up a goal for against vertebrates' nerve system in the very beginning. BoNT did not intend to evolve neurotoxicity to mankind either. Evolution does favor increasing survival of individuals (selectionism) in the cases of macroscopic level, but it is not necessary be the same in the cases of microscopic level (neutralism). Molecular evolution of BoNT genes is not necessary to be related to the question about "if the function of BoNT is critical to the survival of Clostridial bacteria".
Alex: The clostridial bacteria won't die even if they are lacking BoNT family genes in their genome. The DNA mutations happened inside BoNT loci are neither lethal nor hemi-lethal to the host bacteria, so it is very unlike the case of lacking endospore forming capability genes of bacteria (which is lethal or hemi-lethal). If you study the comparative genomics you will know the core genome (minimum essential or needed genes) are mainly related to either nucleic acid enzymes (ligase, recombinase...) or protein related enzymes (endo, exopeptidase...). The molecular evolution happened afterward of host genome must be based on the foundation of these earliest molecules. Most of mutations (large fragment duplication, deletion) happened in genome are neutral and no phenotypic effect to the host. So what are those mutation events for? Actually they are waiting for time, the occasion, and the proper accumulation of mutation events to finally pop out a change in host phenotype.
Goykhman: Alex, I was just saying that i finally understood it
Goykhman: And realistically it is debatable...it is possible that each of those mutations were favorable we just haven't figured out why...
Goykhman: Generation time is so short with that a small advantage could make a huge difference...but I agree it an incredibley interesting non-darwinian toxin
Alex: Yes! 90% of DNA sequences in genome belong to unknown function, not junk DNA. Even though some people regard them as junk right now.
Alex: Maybe say one more thing can help you or Dr. Bromage to better understand my viewpoint. (I knew You already did:)) The genome of clostridial bacteria belong to low GC content. This fact suggested that this kind of bacteria rely on heterotrophic life-cycle more than autotrophic life-cycle. Most of them live in dark soil (no UV-resistance, that is why low GC content) and are saprophytic. They just like other decomposers in the bottom of food chain. They will keep protease related genes as more as possible in their genome.
Goykhman: It's funny that when people have no way of understanding something they give it some dismissive label like junk DNA...This is of course a temporary safeguard to science's ego. Once it is understood it will be given a proper name, but for some reason if science does not have a functional explanation of its presence, it is labeled as having no function...(or junk.)
Alex: I thought you were a pragmatic student, now I gradually found you like to use your idleness for philosophical-like muse. You should quickly get to start your yeast 2 hybids system exps before you got yourself drunk again!!
