Would a trait that's genetics have "circular dominance" be plausible?

Question

Okay, so based on some quick research, there don't appear to be any real-life cases in genetics of "circular dominance" where, for example, allele A is dominant to allele B, B is dominant to C and C is dominant to A, sort of like a genetic game of rock-paper-scissors. However, what I'm wondering is whether there's any reason such a system would be impractical/implausible. Can anyone share any insights on that?

As a side note, I'm also curious to whether the prevalence of the different versions of the trait controlled by such a gene could reasonably remain skewed in favor of one form. (Drawing from the previous example, say, the phenotype that results from an BB or BC genotype being considerably more common in the population of the species than the other two manifestations of the trait.)

Added Details:

The species in question is diploid, so at most a given individual will have two of the three alleles, so three-way interaction in a given individual isn't an issue.

In the particular case of the setting I'm working on the A-phenotype individuals are baseline 'normal' members of the species, B-phenotype individuals have a supernatural ability that causes them to be almost impossible to kill by violence (they die, but regenerate nearby good as new), but which makes them reckless and often outright adrenaline junkies, and C-phenotype individuals have a capabilities that make them superior combatants, but gives them a physical dependency on the flesh of other members of their species. Phenotype C is often discriminated against, but not outright killed on sight, because the B phenotype provides a source of flesh without anyone getting permanently hurt.

Answer 1

Gene regulating protein with differing binding site:

Your gene produces a protein that up-regulates the expression of other genes. Each allele has a slightly different binding site, and thus causes the other genes to be regulated differently.

The three versions of the protein compete for overlapping but slightly different binding sites on the regulated gene. Site (a) binds the A protein, is a weak binding site but highly up-regulates the gene. Site (c) binding up-regulates modestly, but is a tight binding site for C and the binding site overlaps with (a). Site (b) binds B and is also a strong binding site but only weakly upregulates the gene. The (b) site overlaps the (c) site, but not the (a) site.

• AA results in high protein production and the A phenotype
• AB results in high protein production from (a) binding, and the contribution of (b) is insignificant. This results in the A phenotype
• BB gives a low level of expression and the B phenotype.
• BC causes the (b) and (c) sites to competitively inhibit each other, so the net result is overall low expression and the B phenotype.
• CC causes intermediate expression of the gene and the C phenotype.
• AC causes competition for the (a) and (c) sites. Since the binding to the (a) site is weak, and any successful expression from (a) binding effectively reverses the effects of the competition, the overall expression level is intermediate and results in the C phenotype.

There are additional similar regulatory schemes that will have similar results. The addition of tissue or developmental cofactors would allow the genes to have significantly different effects so the phenotypes you want are at least plausible (if we handwave the whole "superpower" thing).

Answer 2

Plausibility: There is no reason why such a system couldn't work in principle. DWKraus's answer outlines one way, and I outline another way below.

So if it can work in principle, why couldn't you find any examples? One reason might be that there are simpler ways of getting three different phenotypes from a single locus, which might therefore be more likely to evolve in the first place. For example, the alternative mating strategies among male Uta stansburiana lizards—which themselves follow a rock-paper-scissors dynamic—are controlled by a single locus with alleles o, b, and y, where o is dominant to both b and y and y is dominant to b. Hence the orange phenotype is either oo, ob or oy, the yellow phenotype is either yy or yb and the blue phenotype is bb only. (Phenotypically, orange beats blue, blue beats yellow, and yellow beats orange, due to the alternative behaviours exhibited by males of each colour.)

So just to be clear, having three different phenotypes, even if they themselves exist in a rock-paper-scissors nontransitive relationship in terms of competitive fitness, does not require any nontransitive dominance relationship at the genetic level.

Skew: There is no reason why such a genetic architecture would necessarily prevent one phenotype from being more common than the others. Let's say the alleles are called R, P, and S. Suppose that both RR and RS individuals are phenotypically "Rock", PP and PR individuals are phenotypically "Paper" and SS and SP individuals are phenotypically "Scissors". Any combination of "Rock", "Paper", and "Scissors" individuals is possible with such a setup; this is trivial since we can just stipulate that, at a given time, X% of individuals are RR, Y% are PP, and Z% = 100% - X% - Y% are SS. But more generally, if we assume random mating between types, there are two degrees of freedom in the system (the proportion of alleles at the locus that are R and the proportion that are P, with the remaining proportion all being S) and these two degrees of freedom are sufficient to produce any combination of X%, Y%, and Z% = 100% - X% - Y% as outlined above.

The question then is whether any given proportion of the three phenotypes in the population can be maintained stably, particularly in the case where the different phenotypes mate with each other and hence heterozygotes are common. If the proportions are being maintained by negative frequency-dependent selection, such that, for example, the fitness of phenotype-"Rock" individuals is higher than average when there are fewer than some optimal proportion of "Rock" individuals (whether that be 33% or anything else), and the fitness of phenotype-"Rock" individuals is lower than average when there are more than the optimal proportion of "Rock" individuals, this leads to a stable maintenance of that optimum frequency. That's because, provided there is at least one homozygote in the population (in this case RR), the average "Rock" individual is more likely to pass on the R allele than any other allele (since they are either RR or RS), so if the frequency of "Rock"-phenotype individuals is below its optimum, the result is that the transmission of R alleles increases above the average transmission of other alleles. Similarly for P and S, therefore, a stable mix of phenotypes can be maintained.

Note that, in order for an intermediate mix of phenotypes to be stable, you still have to explain what leads to the negative frequency-dependent selection in your population. Or maybe the three types live somewhat separately, so they aren't competing fully for the same resources.

Biochemical rock-paper-scissors

There is a number of ways of getting nontransitive dominance among three possible alleles at a diploid locus, so as to resemble the rock-paper-scissors game. I think the most fun way is just to follow the logic of rock-paper-scissors itself!

In other words, let's call the three alleles R, P, and S. They are translated into proteins Rock, Paper, and Scissors, respectively. Each of these proteins has an active site, which does the actual work of producing the alternative phenotype. Hence, homozygous individuals (RR, PP, or SS) have the phenotype corresponding to the allele they are homozygous for. Each protein also has a secondary site, which plays some role in interaction with other proteins.

In PR heterozygotes, Paper's secondary site binds to Rock's active site. This blocks Rock's active site from doing any work, while leaving Paper's active site exposed on the outside of the Paper-Rock dimer. Paper covers Rock. (If Paper is at least as highly expressed as Rock in heterozygotes, then all Rocks could be covered by a Paper.)

In RS heterozygotes, Rock's secondary site allows it to act as a kind of chaperone causing Scissors to fold up into an inactive, mangled mess that can't unfold itself. Rock is unchanged by this interaction and remains free to do other work via its active site. Rock breaks Scissors.

In SP heterozygotes, Scissors' secondary site cleaves Paper into an inactive form. Scissors is unchanged by this interaction, and remains free to do its own thing. Scissors cuts Paper.

Paper cannot cover Scissors because it only binds to Rock's active site, not Scissors'; and Rock can't break Paper, nor can Scissors cut Rock, because these interactions are specific to the very different shapes of the three proteins.

Answer 3

I up voted L.Dutch's answer and you should too, but let's look at this in a different way

Let's assume alleles A, B, and C lead to traits that are valuable for survival for different reasons.¹ In other words, your rock-paper-scissors genetics game becomes unusually environmentally biased.

I wholly agree with L.Dutch's assessment of the problem should A, B, and C appear together, meaning the body becomes susceptible to a tragic weakness because the recessiveness of the alleles are constantly exerting themselves. Or, on the flip-side, none appear at all in which case the poor soul is dead and the condition never passed on.

But in the case where the environment favors A, B, or C, that resolves the rock-paper-scissors problem² while allowing the other two alleles to remain subdued or dormant.

But this means there is an impracticality... and it's not a bad one IMO

It means that migration is minimized because there are environments where, for example, C can't be. Your circular dependency would result in three very separate races of people.

Which also suggests that A and B folks can't easily breed because each generation spent apart reinforces the dependency on the associated allele, right?

It's almost like blood types where (for example and not necessarily a specific issue) allele A people can't give blood to B people because it would kill them. And so on.

---

_{¹ Reasons that I'm not going to hazard here. That's your job.}

_{² Call it JBH's "magnet under the roulette wheel" method of genetic selection.}

Answer 4

It seems reasonable to suggest this could exist, even if we know of no real life examples.

Within an organism there are long chains of chemical reactions which more or less terminate with the final chemical affecting the reactions of the first chemicals. They are self regulating. Systems in biochemistry already do this in principle.

Cycling Phenotypes

Outside of the organism you must consider the species. Perhaps a generations long cycle of sorts could utilize such a genetic scheme. As suggested elsewhere, any cycle in the species must be in response to the cycles in its environment, so this cannot exist alone. My first thought is that competing species both use the scheme. A prey evolves, the predator evolves in response. This action could lead to more environmental stability if your genetic scheme evolved in somehow. Predator phenotype A is well suited to hunt prey phenotype A, but not so well prey phenotype B. Predator phenotype B hunts prey phenotype B well, but not prey phenotype C. And so on down however many links you want. The effect would be a species that cycles through phenotypes. Honestly, I could see this totally existing in real life life, especially among insects, and the only reason we haven't noticed is that it would take a decades long study to show it exists.

Phenotypes for the Super-organism

Between species and organism is what some have called a super-organism. The typical beehive is a great example. Rather than depending on haploid and diploid schemes to produce drones and workers, your proposed genetic scheme produces the phenotypes the super-organism needs. I envision that this would not be a queen-type super-organism, but that most individuals within the super-organism reproduce regularly. Just like the biochemical chains that we know exist, the presence of the final link in the "phenotypes chain" is recessive to the first. The needed phenotypes are self-regulated.

Opinion on using these in story

The first solution has the problem of being a very long lived cycle. There wouldn't be many phenotypes sharing their existence with others. I have a hard time seeing how that might create an interesting story. The only thing that would make sense is some kind of commentary about how sons are and should be different from their fathers, yet, ironically nothing is new and old things that used to work can still work today.

The second solution allows you to have all the phenotypes coexisting. That kind of stuff certainly makes for exciting scifi. However, from a realistic perspective, the chain nature of the scheme makes every single phenotype a well tuned vital necessity to the super-organism's survival. One blip in any phenotype affects the whole chain for many cycles. We see this same problem in biochemistry, and it can take years to reset those systems and bring people back into health. Compared to the haploid/diploid scheme that honeybees use, this phenotype chain seems a good deal more delicate. There's also a fundamental difference that might stand out to your readers. In biochemistry these chains are a function of consumption. They are all metabolism; the processes by which healthy tissue is maintained so as to consume more energy. The final products do affect the first products, but there are waste products all along the way. In genetics, replication is the only function of consequence. It's not a metabolism.

Answer 5

for example, allele A is dominant to allele B, B is dominant to C and C is dominant to A, sort of like a genetic game of rock-paper-scissors. However, what I'm wondering is whether there's any reason such a system would be impractical/implausible.

Let's say that an individual has A, B and C together. None of them would be expressed, due to it being recessive to another. The individual would therefore lack a gene.

We are then left with two options:

• If the gene is not needed for the survival of the individual, it will be removed because keeping it it's a waste of resources.

• If the gene is needed for the survival of the individual, then they will be dead and unable to transmit the feature to their posterity.