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Resheph is also somewhat hinted to be probably at least somewhat a machine. He lived long, tended to the sick without getting infected, the dialog with Yla Haj hints that "healing" should not be seen only for flesh and Rebecca probably had some tinkering relation (also some hints to her connection with Barathrum by the Dialog with one of the Yd denizens.. forgot which one). I would not take the sultan statues too literal, since even the history on them seems to be written from the eyes of the at least somewhat current inhabitants of Qud. A lot of them had accidents with chariots in the world history, but in the Tomb history they are often riding space glider spheres or stuff like that
Stuff like the Gamma World RPG was probably a big inspiration (both seem with the mutation + dark age + Knights of Genetic Purity), but I am not aware of any ingame reason that is *recent* to explain this. What happened is probably so long ago that nobody can remember it anymore (or wants to? Phytas seem really proud), but they might just have atomic bombed the planet a bit after the injunction. What happened directly after and until Sultans is not directly described.
The world has more than just mutations though. Stuff like the Moonstair or many of the normality affected phenomena are also a bit heavy in influence. There is also stuff like holographic bleeding and holographic templars. Both with can kill you and do actual damage.
I am not sure if the mutations players can choose are actual "choices" or just already in the DNA and come up when you "grow older". Since there are a lot of clear mutation strains (like Dromads) it seems those are not still rapid (except for chimeras and maybe Cultists), but maybe the remains from some bigger old event. Could also just be experiments from the eaters having reproduced, but you would probably find a lot more True Kin around if that was the case. Across Moghra'yi, Vol. III: Oth, the Free City might hints that those were maybe not seen eye to eye with some powerful forces though or might simply not have reach Qud much.
His clones are also not True Kin, making it seem like this unaltred DNA is the thing that makes him "True" and not so much how he seems like. The clones have the exact same description. That said, mutated True Kin are still True kin.
I can actually see this being the case with Qud's rampant mutations. Something happened to mutate wide swaths of the world's population, everyone at the time knew about the mutations to the point where it became too redundant and boring to even write about, and now here we are milliennia later with mutants everywhere and no one, not even that ridiculous ancient tree mayor of Ezra, can explain why.
It could very much be that defects were not the minority, but those put you at a disadvantage and a lot of heavily mutated strains that were not able to compete simply didn't make it up to the current time. The event was not like 5 years ago.
These are difficult questions to answer, in good part because afaik we do not have a clear idea of the timeline of Qud before we come along, and in equally good part because, by design, a lot of the history of the world is meant to have been lost to time and therefore difficult to piece together.
From the cherubim in the Tomb of the Eaters being mechanical from the 4th sultan's tomb on, we could infer that the 4th sultan period corresponds to a time where technology (specifically, the "coupling of machine and folk") became a dominant social concern in Eater society. We aren't clearly told so though, so it could very well be that technology was already extremely advanced before mechanical cherubim came into fashion, but if nothing else, it is a hint that cybernetics & technology in general had become a prominent (if not outright religious) symbol of status in Eater society by the time of the 4th sultan.
On a side note, since cherubim come in both biological and mechanical flavors, it is likely that the Tomb of the Eaters had already been there for a while before tech-implanting came into fashion, otherwise I feel it's more than likely that a culture that placed such a big emphasis on mixing biology with technology would have made *all* cherubim mechanical. This doesn't help us much to pinpoint when mutations started to appear, but it does help in pinpointing the relationship of quddians to technology somewhat - as glass zebra pointed out, despite what statues suggest, Resheph himself might have been entirely mechanical : the earliest element of his biography was that he was found as an infant with "circuits in his mouth", and if years in Qud are similar to our real-life years, he's also lived a suspiciously long life.
Mutations are imho tougher to pin down in the chronology. We do know that there were both settlements and Eaters before the time of the sultanate (cf. "In Maqqom Yd"), and there are mentions in "Across Moghra'Yi, vol.I : the Sunderlies" (which, on a side note, is written by a sentient plant, Baccata Yewtarch, and already looks somewhat ancient by the time we get the chance to stumble upon it, which says something of the chronology of sentient mutants in Qud) of a time where a group of people who sound like they're the ancestors of modern-day True Kin (because they're named "true folk", "remained stalwart to their holds" (holds = early freehold/arcology cultures maybe?), and considered other groups and their "cursed offspring" (mutants ?) as inferior and developed a master/slave or master/servant relationship with them (which is where the term "aristocrat" used by becoming nooks might come from ?)).
But that is about all we know. The sultanate seems *relatively* recent in the grander scheme of things ; whatever the sins committed by ancient sultans or ancient Eaters that warranted the wrath of the Coven, I'm inclined to believe rampant mutation was not the punishment - I believe the crime had something to do with Ptoh, and the punishment was the Gyre and the Girsh Nephilim.
I imagine there are many points where other viewpoints would disagree with mine - again, I think the honest short answer is that nobody really knows for sure. For what it's worth, if the lore we find in the various literary classics of the land is anything to go by, I think it's fair to say that mutants have been around for longer than True Kin have : "Across Moghra'Yi" mentions "Ophaedians" (=snake folk) and manscorpions predating what it calls "true folk".
Speaking of which, also from reading "Across Moghra'yi", a possible theory is that modern-day True Kin are heirs to a culture that arised around (or shortly before) the time of the 4th sultan (when technology became prevalent in social life) from a subgroup of humanoids who were genetically somewhat close to real-life humans, were originally related to Eaters (who did not seem like they would shy away from remolding their bodies entirely once they got past the point of replacing their skin or organs with more efficent, synthetic substitutes, to loop back to your original question - because have you even experienced life if you haven't once been a cupboard (Eater statues can spawn as furniture), after all), and had somehow remained isolated from the rest of Qud since then. Coming from a troglodyte and probably very tribal lifestyle, they experienced the sort of brutal first contact with high-end technology from which religious beliefs are born. They took it in stride, came into power, and retained the isolationist and suspicious-of-strangers mindset that they came into the wider world of Qud with - and that isolationist mindset might have been the reason why modern-day arcologies are so different culturally and genetically from the rest of Qud's humanoid population.
If you subscribe to this theory, it's also quite likely that both the Mechanimist church and the Putus Templar appeared at around the same time (4th sultan) the ancestors of True Kin did, give or take a few decades or centuries.