Reproductive capabilites of genetically altered humans

Question

If I have a group of humans that were genetically altered in a similar way, but with different expression of effects in the individual (for example changed eyes, tail growth, wings, scaled skins, possibly other organs non-existent in regular humans...):

would that group be able to breed naturally amongst each other and have fertile children?
would they be able to breed with "regular" humans?
If the answer to (2.) is "yes", how likely is it that the offsprings would be fertile?
If the answer to (2.) is "no", what type of changes would be reasonable in the manipulated humans to result in fertile hybrid offsprings?

score 11 · Answer 1 · answered Jun 29 '20 at 07:48

The answer has to be "perhaps".

Some traits, like eye-colour, are the result of a single gene, there is one strand of DNA that controls eye colour. If you have a functioning copy of that gene you get brown eyes, if no you get blue eyes. (actually, this might not be literally true but it is a reasonable approximation)

Many other traits would be a combination of many genes. For example, a tail would not be a single piece of DNA, there would be multiple genes that could affect the length, shape, musculature and so on. If a tailed person had children with an untailed person, the child would get half of those genes, and the effects of only having half the genes to make a tail might be unpredictable. Probably you'd get a stumpy short tail, but in the worse case you get the tail genes doing something bad, like lengthening the spine or even something which seems utterly unrelated to tails. For example a gene might cause the vertebrae in the coccyx not to fuse, but it also causes the skull to thicken which compresses the brain and kills the fetus. So a second gene is used to turn off the "skull thickening effect. But that second gene, on its own also prevents the head from forming (and the embryo dies very early) You need to have both genes, or neither, and this is a simple "only two genes involved" In real life, even eye colour is controlled by 8 genes, many of which have side effects (or the eye colour is a side effect of the gene)

Wings, for example would require massive gene editing. I would not like to be the child of a winged and unwinged human.

Human eye color is polygenic. There is a complex of genes which determine the level of pigmentation (similar to skin pigmentation), from low pigmentation to high pigmentation. By itself, this factor would only account for light brown to dark almost black. There is a second complex of genes (including Eye Color 1 which determines the structural color due to light scattering; this accounts for the green / blue tint. — AlexP, Jun 29 '20 at 12:00

score 4 · Answer 2 · answered Jun 29 '20 at 11:17

Yeah, I'll go with "probably not".

Different eye, skin and hair color are no big deal, it already happens. The other traits however are a lot different. Let me explain you briefly about genetics and natural hybrids: the absolute majority of animals on earth works on a paired system, in which each animal has a number of chromosome pairs which make up their genome and allow them to function. Upon reproduction, it's gametes have these pairs separated, so that once it meets the other gamete, each half of a pair meets, allowing for a new animal of that species to be born. But if most animals work on paired chromosomes, why don't we see a dog and a chicken in the farm giving birth to a tiny griffin? Because a trait that defines a species is reproductive isolation, meaning that:if 2 species can naturally breed among them in the wild and generate viable offspring with no issues, they're likely not 2 different species.

Now why did I talk about that? Because we need that to talk about your humans: eye color is a relatively small thing that's controlled by a small number of genes. That is why people with different eye color can have kids with no problems. However, traits like scaly skin (a reptilian trait that'd also, most likely, involve the absence of glands in the skin), wings on the back (not only its an extra par of limbs [I'll not discuss the functionality of these limbs], it's a modified pair of limbs with adaptations vastly different from the body) tails (might be the least drastic here, since we did have tails at some point in evolution... Oh wait, it's a fox tail, isn't it?) and other organs normal humans would normally lack (in the best of cases would require special adaptations to be ribcage to be able to contain these organs) are all traits that require a series of genes, and the very existence of each of these traits would require the presence of secondary adaptations of the body to be able to function, from modification of the existent muscles and bones to the addition of new ones to other alterations that might not be noticeable at first. What I mean is that such complex traits, along with their secondary alterations regarding a common human, would most likely require new chromosome pairs altogether. These guys will most likely have more than 46 chromosomes, and the new ones will most likely express traits which negate the expression of normal human traits. But without the other half, these chromosomes won't be able to express properly, thus resulting in normal humans at best and result in several issues regarding malformation and sever health issues which make their survival essentially impossible at worse.

The only way I can see them reproducing with one another without major issues is: having additional chromosomes which completely control these new traits and which usually remain completely inactive without their pairs, while expressing themselves while inhibiting other normal traits in favor of their own when found in pairs (essentially entire chromosomes being recessively epistatic). Note that I'm not a biologist or a genetic specialist, so I can't say with absolute certainty that such a process could work, but to move it does seem in a way to partially solve your issue regarding reproduction (we're already using handwavium to have humans with reptile traits and new organs, so why not?).

So summing up: can these altered humans breed among themselves as well as with normal humans? Realistically no, but if you alter their genome so that all of the changes are causes by new chromosomes that remain inactive when not paired could somewhat circumvent unwanted side effects of such relations. Note however that, having an uneven pair of chromosomes, unless the new one somehow migrate on their own, during meiosis, to one of the resulting gametes, these hybrid children will be infertile (mules are also infertile due to having an uneven number of chromosomes) at best and, should the new single chromosomes try to express themselves, result in malformed fetuses which likely cannot survive more than a few hours after birth in a worst case scenario.

Thank you. I think you brought up some valid points here. That would mean I'd need two types of hybrids - one that is based on humans, and doesn't add too much strange stuff to them, and one that is based on the "supplying species", which would then have some human traits but mostly the FX? — BeeMKay, Jun 29 '20 at 18:36
@BeeMKay pretty much. Whether these new traits can be passed up with more or less ease will be basically related to whether they're linked to new chromosomes other than the ones common in humans or whether they'll just have a completely different genetic makeover and only look somewhat human. The more genetic differences between them, the harder successful reproduction will be. The presence of a somewhat similar species which can still reproduce sounds reasonable, as seen in ligers — ProjectApex, Jun 29 '20 at 19:30
@BeeMKay the key here to get your fertile hybrids is to have a successful child between a human and a "Numan" (new human). Ligers and mules are 2 examples, they're not always viable, but there are instances of successful ligers and mules which were fertile, so all you need is for the Numans and humans to have enough similarities (which is why I suggested new chromosomes being responsible for the new traits) and you'll eventually have what you need to get a group (you will want to make them as similar as possible though, or inbreeding issues might appear if fertile hybrids are too rare). — ProjectApex, Jun 29 '20 at 19:50
Thank you, your answers helped making a choice and had good information. While of course the Hybrid-human offsprings would be cool, I think that actually not allowing it would be more 'realistic'. — BeeMKay, Jun 30 '20 at 00:58

score 3 · Accepted Answer · answered Jun 29 '20 at 14:32

3

If you want it to, then yes. Otherwise, probably not

If you're genetically engineering people to be radically different than humans, you probably aren't trying to create things what will spread through your general population. If I were making monsters (and I have, in stories) I would either design them so they specifically could or specifically couldn't interbreed, depending on my desires. If you left it up to chance, you'd either get non-viable offspring or sterile mules who may or may not have functional parts.

Trying to create super-soldiers? Maybe a master race? You don't want those genes running rampant. Make your alterations to rearrange the genes on the chromosomes, so your resulting gene combinations look more like humans trying to interbreed with goats - not going to happen.
Trying to hybridize humanity with your alien species? Well, then, make a CRISPR-like system where extra DNA is made for this scenario. Have gene sequences tha overwrite human ones, so the key genes are passed on. Have an extra chromosome with sequences that specifically cause it to make an extra copy in any cell with only one. If either parent has the extra DNA, it's passed on to the descendants.

answered Jun 29 '20 at 14:32

DWKraus

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The goal was to have a group of hybrids that can have children amongst themselves (creating a new subspecies of humans, basically. I really like the extra chromosome thing, though I'm not sure if I understand it correctly. If I have one parent that has the DNA overwrite and one who hasn't, would the extra gene then also "correct" the missing pair to match the overwritten segment? – BeeMKay Jun 29 '20 at 18:33
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CRISPR-like tech/genes would allow you to overwrite existing DNA in the resulting children. An extra self-replicating chromosome wouldn't replace any human genes, only add a whole bunch of new ones (that would assumedly be designed to work with each other and with existing human ones). If you want different strains of hybrids, each could have a different extra chromosome. The resulting children from interbreeding would have more and more chromosomes, with possible multimers of genes (side effects?) on all of the chromosomes. – DWKraus Jun 29 '20 at 18:52
Ah, okay, thank you for the clarification. I think that would rule out crossbreeding with regular humans, and just leave the offspring-creation within the new subspecies for the purpose of the story. So that extra chromosome would be without a partner and subesquently leave the offspring not able to survive if crossbreeding happened, because of incompatibility. Exept perhaps in some veeery rare cases, which then would suffer all the usual issues mentioned earlier here. – BeeMKay Jun 30 '20 at 00:49
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Although chromosomes don't usually replicate themselves to become pairs to fill in after meiosis, it would be possible to design a regulatory system to cause the DNA in these special chromosomes to replicate themselves after meiosis to become a pair. Thus, you could mate with normal humans if you wanted (and it was specifically designed to work that way). If there were multiple extra chromosomes, I can only guess about if there might be problems(theoretically no) since this isn't normally how chromosomes behave. The offspring would always be hybrid. – DWKraus Jun 30 '20 at 01:24
What would be the consequence (in real life) if one half of the chromose pair is missing? I mean, we do have this "naturally" and partially in the XY pair, resulting in all sorts of gender related shenannigans, but if you have the "extra info" on it and no magic copy writing systen existed? I'd assume some serious issues? – BeeMKay Jun 30 '20 at 06:31
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Most chromosomal abnormalities result in spontaneous abortions and are non-viable. You can look to Down's syndrome, Turner's syndrome, and Klinefelter's syndrome as examples of viable chromosome abnormalities. Your regular chromosomes have everthing you need to be viable, so if you are short an "extra" chromosome, you'd be free to make up whatever problems you want, from being slightly less alien to children that are completely crippled, assuming they don't die outright. – DWKraus Jun 30 '20 at 20:06

score 1 · Answer 4 · answered Jun 29 '20 at 21:29

Its carries risks

To quickly answer your questions before going into the details:

would that group be able to breed naturally amongst each other and have fertile children?

Only for if each form of genetic engineering is on a different chromosome.

would they be able to breed with "regular" humans?

Only if the genetic engineering is isolate to a single chromosome

If the answer to (2.) is "yes", how likely is it that the offsprings would be fertile?

In a perfect world, 50% chance of genetically altered and 50% chance of normal per trait

For the purposes of this I am going to keep this focused on one example: a genetic alteration giving wings. I will refer to it as the wings gene and have the wings gene traits all be dominant by default. As for whether or not they will be capable of generating enough lift is a totally separate question which I will not cover.

Chromosomes

Humans genes are organized into 23 chromosomes that come in pairs. When breeding one of each pair is randomly selected to be passed on to the child from each parent. As such for this wings gene it needs to not only add wings to the human, it needs to modify the existing bone structure on the back of the human for the wings to lock in, greatly increase the human pectoral muscles (and modify them so they can be linked to the wings), and modify the human to be as light as possible. That is a lot of modifications, and if they are spread out and directly integrated into the respective chromosomes that govern those aspects of the body then it will not be as complex and thus reduce the chance of the alteration indirectly harming the individual.

However if that person was to breed with a normal human the resulting hybrid child might end up with oversized pectoral muscles and no wings, be normal weight and not able to generate enough lift, or could be missing part of the bone modification to the back resulting in the shoulder sockets becoming mutilated. None of these are desirable.

As such all these modifications would need to be on a single chromosome so that it will be all or nothing. Since you cannot directly tweak the existing dna on the other chromosomes, you will be having to add additional DNA that suppresses the normal behavior and development of the body that is present on the other chromosomes, much like how the Y chromosome suppresses the development of mammary glands in males (most of the time, and it does not stop the formation of the nipples). That is a lot of extra DNA and the problem is fitting it all on one gene. There are two options for this:

Option 1

Have one copy have a normal chromosome paired with a wing gene chromosome (similar to how the X and Y chromosome work). This has the benefit of keeping the total amount of dna in the cell roughly the same. The problem is that it would behave like the Y and X chromosomes do without the safe guard that they have (two males cannot breed together and thus cannot result in a YY pair). This is bad since a genetically altered person could only safely breed with a normal person to ensure that they get the normal gene that can be paired with the winged gene. If two people with the wings gene were to try and have a kid there would be a 25% chance of the fetus having two wings gene which would be fatal or carry severe disorders.

Option 2

Keep the normal DNA and add all the wings gene DNA to it. Thus if they have two copies of the normal + wing DNA they are still good. So anyone with the alteration can safely breed with anyone who has it or anyone who does not have it. If a hybrid was to breed they would have a 50% chance of passing the wings gene along (and two hybrids would have a 75%). Sadly though, this carries its own problems.

The size of the nuclei in the cell is not changing, but now there is more DNA in it. This will increase the chance of something going wrong during cell division. This can possibly lead to health issues, with the worst cases being cancerous cell growths. If this happens early on in a pregnancy or with the sperm or egg then it will likely result in a miscarriage or severe birth defect. There are lists of various genetic disorders that can be found so I will not go into what they are. These lists do help with world building too, if the wings gene happens to be on chromosome 5 then does it increase or decrease the chance of Cri du chat syndrome? How much of a chance these problems have of going up I cannot say, but since this is your world you can decide how much of a factor you want it to be.

Conclusion

As such I recommend for it to be believable and get what you want, each alteration is coded onto a different chromosome and preserves all the normal DNA on said chromosome. Any genetically modified human might have these cool amazing traits, but they also are more prone to cancerous growths, miscarriages, birth defects, and genetic disorders.

Thank you. If I'd reduce the tinkering to 'just' reactivating/deactivating sequences that already exist in the human genome but are switched off, would that reduce the risk for hybrids breeding amongst themselves? Also, why would hybrids just have 75% chance of passing off a trait if they both carry the changed gene? — BeeMKay, Jun 30 '20 at 01:08
If two hybrids have one gene with the modification and one gene with out the modification, then there is a 50% for each to pass the modification along to the next generation. So there is a 25% of two modified genes, 50% of one modified gene, and 25% chance of no modified gene. Since you only need one modified gene 75% chance. — Anketam, Jun 30 '20 at 02:11
@BeeMKay if it is reactivating and deactivating sequences, note that genes are a scattered and jumbled mess. So the sequences that would need to be activated would likely be scattered across many chromosomes. So your hybrids can run into issues if they only inherit some of the activated sequences. — Anketam, Jun 30 '20 at 02:16
Ah, I see. Though you're describing dominant genes (if I recall my school biology correctly); the traits could also need to be expressed in both copies of the chromosome pair to work.Though that would then probably also lead to all sorts of genetic malefunction issues... — BeeMKay, Jun 30 '20 at 06:36