What would determine the rate that a hereditary condition reveals itself after years of dormancy?

Question

Long ago, an Eldritch deity was summoned to the city of Innsmouth within a ritual circle, where it was killed and consumed by the population. Devouring the flesh of the deity increased the mana supply of the individuals to astronomical levels, strengthening their arcane abilities. As the population grew in power, the prestige of Inssmouth increased in the world. As all inhabitants benefited from their mana supply increase, the city became known as a center for magecraft where the most powerful mages were located. This lasted for a period of 500 years, as the population passed down their arcane power to their descendants.

However, over time, problems started developing in the city within the past 50 years. The current population began suffering from defects and mutations.It turns out that the increase in mana from the god began to mutate future generations. Individuals with heavy deformities became twisted and inhuman, as their mental faculties decreased while becoming animalistic. More defects in the gene pool began showing up as a significant portion of the population gave birth o monsters. Ultimately, this ended with the entire city becoming filled with debased creatures with no semblance to humanity.

Somehow killing and consuming the pieces from the god had an effect on the genes of the population. This hereditary illness was passed down to their descendants, but didn't reveal itself. The chaos of the mutations occurred suddenly and quickly after centuries of stability. What would cause this massively delayed reaction?

Answer 1

It looks like you are seeing for the transition from a genotype (where the changes in DNA are in the genes but don't necessarily express themselves) to a phenotype (where these same genes give rise to the monsters)

This is most easily explained through a new gene expression where the existing genes suddenly start producing certain proteins that lead to the mutations.

There are many ways to regulate gene expression and many of these are very subtle. For a gene to stay dormant for 450 years and then suddenly express itself through the entire population you'd expect that something in the environment is to blame, otherwise you'd see it after x generation instead of years, or only in a sub-population that mixes with another group.

As your world has magic this is probably the easiest explanation. Did someone else attempt to summon the god? Did someone do a ritual sacrificing members the race? Did a new kind of spell come into vogue? Did they find a certain crystal that ups your mana pool if snorted?

For a real-life example: in the 1950's a new medicine was marketed to help with a wide range of issues, including anxiety and morning sickness, and actually helped against those things! Amazing stuff. However this drug also interferes with a protein called SALL4 which, while not that important in adults, is vital in unborn babies for the proper growth of limbs and other structures. In the end over 10.000 children were born with deformities, a lot of them perishing shortly after birth from the effects.

Answer 2

Mana magnet.

God power is heritable, as you establish in OP. Mana can cause mutations; also in OP. The god power grants mana but also serves as a long term mana attractor or sink. Subsequent generations in this town have more power than their ancestors thanks to this god meat effect.

The increase gets to a point where it is too much for biology to handle and things start to break. That is where you are. Mostly this makes degenerate monsters.

0.1% of these mutants will not be monsters, but new gods. When the new god comes into its own, it will be hungry. The degenerate monsters will be happy to feed it with their own flesh, and that of any of their less willing mana-rich relatives they can catch and bring with to the coming of age ceremony.

This event is what the Foundation (working thru the federal government) was trying to avoid, to no avail. Fallback plan: the best way to fight a god is with another god. They have an Innsmouth child with potential whom they are trying to raise as fast as they can, on a diet of mana-rich god meat from various sources.

Answer 3

Natural Selection

The same genes that manage Mana capacity are the same genes that cause monster mutation. if enough genes are activated at the same time of course. The initial Devouring gave different mutations to all the families.

The increased mana combined with the new magecraft prestige caused mage families to arise and political marriages or marriages for power between mages ensued. Fast forward many generations and enough genes have been activated in any individual that almost any combination between members is resulting in monstrous creations.

450 years is about 10-15 generations. Assuming the most powerful mages married amongst themselves to produce the best possible offspring (and highest mana pools 100% precisely and unique gene combinations), for 10 generations you could assume 2^10 gene applications or 1024 unique genes that are a mana mutation (32,768 for 15 generations). Likely though, pairings would duplicate potential gene combinations meaning this is an upper bound.

So monsterification happens after a number of combined gene mutations occur. Let's say it only occurs after 666 god gene mutations which could easily occur within your 10-15 generational gap and once the genes are that widespread almost everyone should have a high combination of genes that could create monsters.

Answer 4

Tolerance, science, and rationality arose.

For most of human history, we knew how to handle witches. You get some wood, toss the witch on the wood, and burn them. This served as an effective way to handle people with mutations from the consumption of the god, and limited the prevalence of the mutations.

The magic relies on multiple homozygous dominant gene sequences being expressed together to power the magic, stabilize the magic, regulate the magic and do various things. Each of these mutations has various benefits for people like enhanced charisma or strength or resistance to aging which helped people if heterozygous, but side effects if homozygous.

However, in the modern era, the old ways fell out of favour. People felt it was 'immoral' to burn people because they violated the purity rules of a religion set up by a bronze age semitic deity and mystical appeals to non existent magic. Those with mutations were given medical care and mental health care, and those with minor physical mutations were tolerated for their small acceptable deviations.

This backfired, as horizontal gene transfer began.

The various gene lines of the people started to converge, and several more powerful individuals were born. These individuals had reasonably complete genetic sequences related to the elder gods, and with this they could do horizontal gene transfer. Most gene transmission in humans involves gametes combining, genetic twists in the womb, and similar things.

The mutant monsters also had viruses that could transmit altered genetics. By biting people, sex, blood transfer, and other methods they converted the remaining people. The tolerant, rational, and scientific people were the first to die, and soon the city died under mutating virus of the old ones.

Answer 5

All the Eldritch genes become transposons in testes and ovaries (as detected by transcription factors). This means that anyone with Eldritch heritage passes all of it into all of their gametes and therefore children. The first generation mages only had a few relevant proteins each, but each successive generation comes closer to the full set. And when they get close enough, the Old One's non-material aspects (of course it's not completely dead) get to start shaping their morphogens.

This means that if someone left the city before things fell apart, their children would be as powerful mages as they are and not at risk of further degradation provided they married people who were untouched by this.

The setup is complex enough that it was probably a deliberate plot by the Old One. Who, unlike those who ate it, understood genetics.

Answer 6

Environmental factors have changed.

Many genetic disorders only cause problems when paired with the wrong environmental factors. Take Celiac Disease for example. It is a genetic autoimmune disorder that causes your immune system to attack your own Gastrointestinal System... that said, it only does this in response to the presence of gluten; so, you could have an entire civilization full of people with Celiac Disease and not know just because they don't grow or eat wheat.

Likewise, when your people consumed the dead god, they changed their DNA to include a disorder that causes monsterism... only the thing that triggers monsterism was not present in their society. Without more information about what your time period is, it's hard to say what your trigger should be, but pretty much every generation of people likes to expose themselves to stuff that older generations didn't have much contact with. Our generation has Wifi everywhere, the previous generation had leaded gasoline, before that there was the introduction of incandescent lighting, before that it was mercury based medicines, so on and so forth... You just need to take your targeted time period, find whatever defining inventions happened at that time in history, and the find a logical correlation between that invention and the autoimmune response or what not that turns you into a monster.

Answer 7

Mitochondrial DNA is the key

Mitochondrial DNA is a subset of cellular DNA that is (in almost all cases) passed from the mother to her offspring, differently from nuclear DNA, which is a recombination of father and mother's DNA.

Citing from the wikipedia article (the mitochondrial bottleneck, emphasis mine)

Entities subject to uniparental inheritance and with little to no recombination may be expected to be subject to Muller's ratchet, the accumulation of deleterious mutations until functionality is lost. Animal populations of mitochondria avoid this through a developmental process known as the mtDNA bottleneck. The bottleneck exploits random processes in the cell to increase the cell-to-cell variability in mutant load as an organism develops: a single egg cell with some proportion of mutant mtDNA thus produces an embryo in which different cells have different mutant loads. Cell-level selection may then act to remove those cells with more mutant mtDNA, leading to a stabilisation or reduction in mutant load between generations. The mechanism underlying the bottleneck is debated,[40][41][42][43] with a recent mathematical and experimental metastudy providing evidence for a combination of random partitioning of mtDNAs at cell divisions and random turnover of mtDNA molecules within the cell.[27]

The mana is passed through mitochondrial DNA, which means, only women can pass it: the children of a man from Innsmouth who marries a stranger woman would be normal people, without any magic enhancement.

But this strong presence of mana somehow inhibits the mtDNA bottleneck. For instance, it could be a kind of revenge from the eldritch entity (or maybe its way to reproduce), whose mana "timed" the subsequent mutations of DNA so that they could create, after exactly N generations, the monstruos creatures.

Answer 8

Trinucleotide Repeats:

The Eldritch god generated new genes and proteins, and altered existing genes, such that the mana manipulation and generation of the people who consumed it was vastly increased in a heritable way. Perhaps this worked like CRISPR, transforming the adult cells and the first generation, but creeping into the germ line of the succeeding generations.

However, these genes contain trinucleotide repeats, and these repeats expand in a fairly predictable way. This means that the trinucleotide repeats alter the effects of these genes over time, either disabling them or magnifying the effects (depending on how you want to handle it). I can imagine a number of ways this could play out.

• The trinucleotide repeats change the genes so they reactivate the CRISPR-like functions from the god, lying dormant in the people. These activate like viruses, spilling into the environment and infecting animals. They then begin incorporating the animal genes, reinfecting humans, and replacing the homologous human genes with animal ones. Lethal alterations die, while viable ones copy the genes and the CRISPR-viruses spread them throughout the populous.
• The trinucleotide repeats expand the mana power until the individuals begin uncontrollably opening micro-portals to the non-physical true manifestation of the god. The god then begins directly altering the DNA of the people around it. The next generation is massively mutated.
• A lot more of the god came along than the few genes expressed. Hundreds of silent unexpressed genes are inserted, but until the trinucleotide repeats convert one of these genes into a regulatory protein, these additional genes went unexpressed. Since trinucleotide repeats end up with many slightly different trinucleotide counts, each level of expression results in different "mutations."
• One school of thought is that introns may contain vestigial DNA from ancestors (not generally assumed anymore, but it works for this question). Like the last point, at a certain threshold "new" ancient genes are turned on. As the trinucleotide repeats activate these genes, ancestral bestial traits emerge, differing by which versions of these genes are present in each person.