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Context

I plan on creating a world with two human populations, one that would have their respiratory and blood systems genetically modified (suited to be more resillient against oxygen poisoning caused by higher oxygen concentration in the atmosphere), to make them better suited for their new world, and the other being unmodified - a human as regular as you or me. The difference itself would arise from the fact of the gene modding ones children would be of personal, free choice, so some may choose to have "pure" children, while others may choose to have engineered ones.

Question

Could a population of genetically modified humans still crossbreed with unmodified humans, since those are still same species, or not, due to difference in the genetic material? If yes, would there be any potential health issues present in children, like higher cancer risk or decreased fertility?

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    $\begingroup$ Question: "The gene modding would be of personal, free choice" implies that it occurs to adults. Is that the case? If so, you're deep into magic territory, and whether or not the populations can interbreed is entirely your choice as the author. $\endgroup$
    – jdunlop
    Commented Mar 8, 2023 at 21:18
  • $\begingroup$ @jdunlop Oh no no no, I meant that it's someone's responsibility, and since parents are responsible for children, they'd also choose whether they want their direct offspring to have that or not, let me clarify that quickly in the post $\endgroup$
    – Yulian
    Commented Mar 8, 2023 at 21:22
  • $\begingroup$ Genetic engineering isn't really a matter of choice - you either have modified genes and pass them on, or you don't. There is no mechanism to consciously select to pass on a gene or not, other than to genetically engineer your gametes to reverse the modification. $\endgroup$
    – Monty Wild ♦
    Commented Mar 8, 2023 at 22:45
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    $\begingroup$ In other words, it becomes up to the writer to decide if there are problems associated with it or not. Take a look at the genetic differences in the oxygen tolerance of those living on the Tibetan Plateau with "normals". There aren't problems interbreeding in that case, but if you want there to be issues in your story, then it shouldn't be hard to justify. $\endgroup$
    – Escaped dental patient.
    Commented Mar 8, 2023 at 22:50
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    $\begingroup$ I think he means that the parents will decide if they want their children modded, like in GATTACA. $\endgroup$
    – Robert Rapplean
    Commented Mar 9, 2023 at 0:06

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It would depend on what sort of gene modding you intend the modified humans to have.

If it is introducing multiple new genes, say from other species or the like, then interbreeding would likely be much less common, as you would essentially be creating a new species. Interbreeding would perhaps still be possible depending on the exact changes, such as we see between similar but not identical species such as horses and donkeys, or tigers and lions, but with much lower success rates than normal, and any children would probably be sterile and potentially have many developmental problems.

If however it is similar to how we do genetic modification today, that is we don't introduce new genes altogether, but instead replace existing genes with genetically modified versions with a specific version of a genetic allele that is more functional in some specific way, say it is better at processing oxygen, or better at processing or breaking down any toxic metabolites etc, then interbreeding would be perfectly possible at the same rate as normal couples. However the resilience that the genetically modified parent was modified for would become diluted out over several generations.

This genetic modification could potentially lead to other problems though. As we know, inbreeding within families is generally frowned upon as it increases the likelihood of genetic disorders. If we have a large genetically modified population, then they will have been modified to have the exact same versions of many genes, thus increasing their "relatedness", and potentially increasing the chances of genetic diseases in their offspring should genetically modified humans interbreed with each other. The rates of genetic disease would likely higher than in the general population, and this would even provide an incentive for the genetically modified population to not interbreed with each other, and actually encourage crossbreeding with "normal" humans. This would be less of an issue if the genetically modified humans are homozygous for the mutations (i.e. they have 2 identical copies of the modified gene), as it would mean that having 2 identical mutations is not a problem. However it would be a serious issue if they were heterozygous (i.e. they only have 1 copy of the modified gene), as this would mean that having 2 copies is "too powerful" and causes serious problems, this is a serious issue in many human diseases, the most famous being sickle-cell-anaemia, where having 1 copy of the sickle cell allele makes the person more resistant to malaria, but having 2 copies can cause serious circulation problems.

Another factor encouraging the "crossbreeding" of the genetically modified humans with normal humans, if we are assuming that all the genetically modified population have the exact same modified genes, this is essentially playing with evolution. Any change in environment could seriously inhibit the genetically modified population who are specifically designed to thrive in one specific environment much more than the "normal" population which would have the normal mix of genes and thus are more adaptable and "generalist", and would likely be much more flexible in genetic terms.

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  • $\begingroup$ Regarding your last paragraph - the modded humans are supposed to be the generalists of that planet, the same way we, unmodded ones, are of Earth. The "vanilla" population will probably have to stick to highlands (at 2km above sea level the pressure would equal that of the Earth, though the concentration of oxygen will still be higher) or risk getting oxygen poisoning, which spins your point around and would probably create an incentive for "normal" humans to cross with the modded ones $\endgroup$
    – Yulian
    Commented Mar 11, 2023 at 13:58
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The answer to this question is:

It depends.

If the genetic engineering is performed as modifications in place to the existing genome, in such a way that genes are added and certain genes that all normal humans have must be modified or inactivated in both copies, then it is likely that a cross between an engineered and un-engineered human would be non-viable or in some way disadvantaged. This represents the simplest way of performing genetic modifications, basically by creating a new species.

However, there is another way...

An entire artificial chromosome may be added, with all the necessary genes to block expression of unneeded genes on the pre-existing chromosomes and to produce new proteins for the new functionality. This chromosome would need to exist in duplicate, the same as every other chromosome, so how could a cross between an engineered subject and an un-engineered subject be viable?

The answer to that is basically to engineer that in. There are several possible mechanisms, but they all amount to checking for the presence of two of the new chromosomes in a fertilised ovum, and either getting rid of any excess, or duplicating a single new chromosome.

Effectively, during meiosis, the new chromosome could be replicated twice by means of a new start-sequence and a modified initiator protein, and then if extra copies are present in the single-cell zygote, the extras could be destroyed by a targeted DNAse.

Alternatively, if the single-cell zygote had only one copy of the new chromosome, the new start sequence and modified initiator protein could start a round of DNA replication that would affect only the new chromosome.

Effectively, with this engineered new chromosome, even if only one parent possessed it, it would still be passed in duplicate to every child, with both copies coming from one parent. This would result in the new chromosome spreading rapidly through the population from generation to generation, as long as the modified and unmodified subjects are still willing and able to reproduce together.

Additionally, it could also be possible to engineer a mechanism by which engineered drugs could toggle the presence or absence of the new chromosome in gametes, so it could become a matter of choice - at least for males, since females produce all of their eggs prior to birth, at least in unmodified humans.

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    $\begingroup$ "It Depends" is an indication of the right answer. 🙂 $\endgroup$
    – PipperChip
    Commented Mar 8, 2023 at 23:26
  • $\begingroup$ "It depends" is right, but there's no reason to believe that in-place modification would be fine. $\endgroup$
    – Jack Aidley
    Commented Mar 9, 2023 at 9:55
  • $\begingroup$ Rather than adding a new chromosome, what about adding the new genes to the end of one arm of an existing chromosome? They'd have to be engineered to be insensitive to gene dosage, since homozygotes (people that inherited the mods from both parents) will have two copies of the new genes, and heterozygotes (people who inherited them from just one parent) will only have one copy, but other than that it shouldn't take anything fancy. $\endgroup$
    – Gordon Davisson
    Commented Mar 10, 2023 at 1:52
  • $\begingroup$ @GordonDavisson What you're suggesting is trickier. Having genes that are insensitive to ploidy is all very well in the early days, but your modification is going to be inheritable, and mutation will occur. You need a new chromosome so as to be able to create 2 duplicates in case the other parent doesn't have the new chromosome. $\endgroup$
    – Monty Wild ♦
    Commented Mar 10, 2023 at 2:01
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This is up to the author. I believe that genetic modifications in this form CAN be made, and still have the children be inter-breedable.

The problem comes in if you have multiple gene sequences that work together. If you have a single gene that controls how much oxygen your blood cells can carry, then that's an all-or-nothing kind of thing. If that gene is only useful if you also have the "more aveolas" gene, then offspring could have one or the other, but the BbAa combinations don't sound like they would be fatal.

However, let's say that your "more oxygen in the blood" gene also depends on a special uptake protein at the cellular level for receiving oxygen from those new, better blood cells. If you have either of those, but not the other, then the fetus would suffocate before it was born.

There are worse consequences. Let's say you have a "stronger muscles" gene and a "stronger tendons" gene. The first without the second would result in kids that, when they learned to walk, would be prone to rip their tendons. The reverse condition might result in kids that suffer pain any time they move, due to brittle tendons or some such technobabble.

Thus, I would say that there are some mods that can safely interbreed, mod packs where you're rolling the dice if you have kids, and mod packs where you lose all ability to interbreed (super-soldiers or aquatics, for instance).

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  • $\begingroup$ Yep, one in ten "crossbred" children makes it and is healthy, but the other 90% suffocate quickly upon birth (or in the womb) due to non-matching oxygen infrastructure in the body. $\endgroup$
    – Hobbamok
    Commented Mar 9, 2023 at 9:41
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Not what you asked, but I'll give the answer anyway...

Legal "side effects"

The modified genome might be patented. Now, with our current bio-patent laws, things are a bit...fuzzy here. The human body or human genes may be except from patents, but there's still room for interpretation out there. OTOH, the modded genes are not originally human genes, and might enjoy protection. Now, patent protection usually applies to commercial use of the patented "method or apparatus". Mom and dad having a bit of adult fun is usually not a commercial activity. However, a clever lawyer might construct a case where a person, when produced with the patented genes, could be legally barred from any commercial activity (with the argument being that the improved patented genetic material allows for better work, causing the offspring to be more profitable).

Now, this is all speculation, both today and the future you are going to depict. Laws often change quite a bit over time.

But there could also be another issue. Modified persons might require special food or some special treatment or medicine to stay healthy. Or it might be the other way around, that vanilla people require such things. It might be that hybrid offspring will require such things as well.

Now, if the company which provides that special food/treatment/medicine also holds the bio-patent, they might refuse to sell to hybrid ("unlicensed") persons. Basically, letting "unlicensed" (though maybe totally legal under the law) offspring die in order to discourage hybrid breeding.

Reading though my writings above, I guess I spent too much in the presence of evil overlords.

In any case, regard this less of an answer to your question but more as a possible source of inspiration.

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    $\begingroup$ Sounds like a good idea for some sci-fi setting where humanity keeps developing here on Earth, but it won't fit in the setting here $\endgroup$
    – Yulian
    Commented Mar 11, 2023 at 13:52
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Most likely not

And that by definition makes them a different species! The issue is that having greater resilience against oxygen poisoning would require changing quite a few genes, as the issue is not only in body's respiratory and cardiovascular systems but deeper into cell metabolism. You would have to modify some genes and then add some new ones. And as soon as you touch on that you will get issues with cross-breeding.

Rule of thumb is that greater the change, less likely it is to have viable cross-breeding. On small changes there is no issue, on bigger ones you can have offsprings, but they are infertile, and on bigger yet even that is impossible. And your suggested change is not all that minor.

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