-Jumps in late- Some thoughts:
Insane wanderer said:
If the FEV virus "repairs" its host's gametes by restoring their chromosome complement, would sterility necessarily befall the parental generation? Wouldn't the F1-generation simply become tetraploid? In fact, autopolyploidy would probably naturally enhance the FEV effect by making the offspring larger due to the increase in cell size (caused by the repression of certain proteins which facilitate the cell's movement through the G1 phase of mitosis, when growth occurs) and also more fit due to the increased expression of all the host's genes.
My understanding of FEV is thet is doubles all the DNA it finds, including the haploid ones in the reproductive system. This in and of itself would disable the recombination machinery and make a zygote unable to divide even if fertilization were successful.
Kharn had a thread on this subject back in Nov 2003 in in Gen Fallout Dis, look it up. Increasing the cell size wouldn't occur in my understanding; the DNA makes up a relatively small part of a cell, and the increased size would increase an average cell's mass by...2 percent? Increased expression of host genes is also the hallmark of cancer, keep that in mind. Just because genes are expressed more doesn't by any means indicate that the organism is better off.
Sure, the four homologous quadrivalent chromosomes forming during prophase in meiotic cells of F1-generation individuals would be less stable than bivalent ones and thus more prone to fertility-reducing segregation errors. It's a short-term process so the mutants are destined to die out anyway but perhaps not after just one generation, as the game tells you.
Fertility reducing segregation errors would only occur in sex cells that could recombine properly, which wouldn't happen due to the extra set of DNA. Define short-term process for me, I don't follow.
Occasionally accidents happen and the bivalent's separation doesn't go through, creating a gamete with one chromosome more or less than it should have, resulting in various genetic disorders. If this were to happen to all chromosomes, a whole new set would be created. A normal, haploid germ cell fertilized by one of these would yield a triploid organism, assuming that the individual survives. If both gametes were diploid, the offspring would be tetraploid. The condition is called polyploidy and is infrequent in many animal species but quite common in plants.
Also creates Donw-syndrome conditions (XXY iirc) and fragile X syndrome, among many others. But none of this has to do with FEV. I've thought of the whole plant thing too, I wonder is FEV would sterilize them?
Just to clear it up, someone exposed to FEV would belong to the parental(P) generation, while its potential offspring would be F1.
P is also called F0 (at least here). Keep in mind that many genetic abnormalities do not show up until F2 either.
Sander said:
Now, I'm not a biologist, so this may be incorrect or sound a little fuzzy, but I recall that FEV had been mutated due to radiation. Would this not effect the sterility of mutants? As in: the sterility isn't necessarily caused by the way in which FEV operates, but because of what it does.
This is also true, and I do not remember if a Bible or something in game explained this. Also, radiation is just one mutagenic method. In that sense we are all mutated everyday when we go under sunlight. Radiation is also a very inexact mutagen, and it is possible that the FEV creators were unable to determine exactly what the radiation did to the virus.
insane wanderer said:
Based on what the Glow computer says, they're not damaged per se but replicated, resulting in aneuploidy: wrong amount of chromosomes.
Okay, noted.
The concept of a virus "healing" its host is clever, since it ensures its own survival in the process. It kind of makes sense if FEV happens to be a provirus, meaning that it integrates itself into the host genome, instead of taking over a cell's replication machinery outright and eventually causing it to burst, prompting the immune defense to react.
This is a very simple interpretation of a very complicated concept, but a good synopsis nonetheless. Fact is it has been hypothesized that viruses are to blame for much genetic transfer between species, families and orders. These transfers are bad for the individual, good for the species because they introduce variation. Also, FEV is probably a DNA virus, because RNA virions are often too small to encode the immense amount of information that FEV would need to include in order to do its job. I would guess it is of the...(checks Fields Virology)...
Herpervirus family, because of the and function of these viruses.
As for increasing mutant fertility, I guess the most straightforward approach for giving them the chance to procreate would be to isolate two germ cells, extract one set of chromosomes from each and then do an in vitro fertilization, i.e. in a test tube.
True, but how would you remove one of the chromasomes? They are identical afterall, sort of.
This is pure conjecture but another way to go about it could be to utilize something called restriction enzymes. R-enzymes are a bacterial defense mechanism against viruses. They degrade viral DNA by recognizing specific sequences and cutting it there. I'm not sure, but it could be conceivable that strains of bacteria have developed in the Fallout world with the right type of r-enzyme against FEV. If the proper gene were identified, isolated and inserted into the appropiate stem cell in a foetus, maybe the virus could be neutralized.
Restriction endonucleases (/show off) wouldn't know if it was cutting the original or FEV induced strand. However, secondary and tertiary modifications to the histones of the original and induced strand may very well be different; if you could find or engineer an enyme that would preferentially cut one variety of modification over the other, your theory holds water.
I know this is just circumventing the problem and hell knows what the effects would be.
Again true. Messing with developing embryos is inherently risky and complicated work. Adding enymes, and such may alter other factors in unknown and important ways.
What led you to this line of inquiry insane wanderer?
Ratty said:
Methinks we are delving way too deep into genetics here. Keep in mind that Fallout was designed by game developers, not by people with PhD in biology. From what's said in the game we can draw that FEV is a retrovirus that upgrades infected cells to quad-helix structure and possibly repairs inherent genetic flaws (otherwise the tetraploidy would likely lead to accumulation of negative or even lethal mutations). I believe it is also said that FEV is capable of fixing only cells that have exactly 46 chromosomes, so gametes (and possibly aneuploid somatic cells) are destroyed rather than evolved. Insane Wanderer stated that the Glow computer says reproductive cells aren't destroyed but replicated, but I don't recall reading that anywhere - can someone with a savegame near Glow check that? If my memory is correct, then it would explain a lot of things, including why the parental generation is rendered sterile. If not, it creates a whole load of new questions. If a) FEV doesn't destroy gametes but makes them diploid, and b) infected organism gains improved regenerational abilities (thus becoming virtually immune to genetic degradation) - then wouldn't the fertilized egg retain the same qualities and be capable of repairing errors that were inflicted during meiosis I? I speculate that perhaps the parent's antibodies - being apparently powerful enough to repell virtually any "foreign" cell, from infectious bacteria to organism's own cells that became altered beyond repair (ever heard of a supermutant with cancer?) - indiscriminantly destroy the parent's own gametes, since they are likely full of errors due to unstable, error-prone tetrades formed in meiosis I. But this is all pure speculation and game developers themselves would probably wonder what the fuck we are talking about if they saw this debate.
True and true. Abs have been known to attack fetuses (or rather embryos). Of course this whole FEV virus is pretty pointless without examining the effects of the immune system on the new 'quadraploidy' organism, but that's for another pointless discussion.
Also, nothing in the game really indicates that radiation caused multiple FEV strains to be created (though it's very likely to happen, as FEV is an RNA virus and thus more prone to mutations).
RNA virus you say? okay, but my previous points about DNA vs RNA still stands.
If anything, I'm pretty confident that supermutants were created using the original strain of FEV, since Mariposa vats likely weren't overly exposed to radiation.
Hold on a sec. I admit my understanding of FEV in teh Fallout universe is limited, but are you saying that radiation was never a part of the original FEV? This would answer alot of things.
Large quantities of the virus that leaked out of the facility were much more likely to mutate into new strains, however, and I imagine that's why so many diverse mutations occured throughout the wasteland. Damaged and potentially defective strain of FEV, combined with host cells that were badly damaged by excessive amounts of radiation, are what probably led to inception of ghouls, radscorpions, brahmin, giant rats and other creatures.
Sure, why not? In the context of ghouls et al existing this is as plausible as anything.
What I'm wondering about is to what extent all these creatures were affected by FEV, and how come they weren't rendered sterile?
I would assume that the mutant FEV lost it ability to double host DNA, but reatined its ability to grant strength, intelligence and spotaneous mutation. Often viruses lose particular traits over time, and if the DNA doubling effect was not able to be passed on it would be evolutionarily disfavored, leading to the DNA doubling deficient strains overtaking it as the dominant strain in the wastes.
It seems reasonable to assume that all these species have become tetraploid, which gave them hardiness and resistance needed to survive in the wasteland.
Tetraploidy in and of itself would only give advantage if the orrganism could reproduce and the benefits were not derived form another aspect of FEV. Since original FEV causes sterility, I propose that the DNA doubling is a side effect, unecessary and indeed counterproductive in a 'free-living' organism, and was thus selected against.
Brahmin's two-heads are another curious twist - my guess is that normal, domesticated cows already posses a recessive gene for two heads
Just because pictures of two-headed cows exist doesn't mean it is a recessive trait. Those animals are the result of incomplete and/or incorrect division of a zygote, nothing more. Funny though!.
and evolution to quad-helix structure allowed this gene to become dominant. It is definitely a useful trait, since it allows the cow to take in twice as much food and water, which is crucial for survival in the wasteland.
If anything another set of chromasomes would further 'recessify' a gene, since two copies of the dominant gene are now present. Besides, FEV is designed to make things hardier in the short term, so recessive genes would presumably be something they would try to further reduce. Note though that as a population recessive genes are an advantage, but for sterile creatures, who cares?
As for restoring mutant fertility, I doubt anything can be done in that respect. Insane Wanderer offered an interesting idea that might still allow them to reproduce, so I will expand on it with my above speculation. My theory assumes that supermutants are still capable of producing gametes at some point, so why not try and extract them before they are destroyed by the parent's metabolism, and then fertilize the egg artificially? The fertilized egg should be capable of self-repair. If not, we can always extract appropriate proteins (or whatever is responsible for DNA repair) from a parent's body and inject it into the fertilized cell.
Or better yet, just extract sperm or egg cells prior to dipping and doing IVF on them?
When the fetus grows, it can be implanted into the mother's uterus. Keep this up for a few thousand years, and maybe a random mutation might lead to birth of a species of fertile supermutants, which would undoubtedly quickly replace the "original" supermutants through the process of natural selection.
But as I said before the mothers immune system may react especially badly. And if left to nature it would take much less time for this to occur, since you are overcoming the biggest obstavle to its occurance artificially.
Longest Post EVAR!
