Gene Swapping via Sperm Absorption of DNA

On one hand, this is an important step forward in genetic engineering that will make it easier to develop farmed organs for transplant.

On the other hand, it’s fairly creepy as a technology and making genetic hybrids with farm animals is likely to ‘have issues’ such as moving animal diseases into human hosts.

On the third hand (hey, it could happen, and sooner than you think…) it shows a potential way for mammalian cells to do what bacterial cells do: swap DNA around.

Perhaps even ‘by accident’ in nature. In short, not all interspecies ‘hybrids’ need to be 50-50 mixes from two parents. Unlikely? Certainly. Impossible? Well… that remains to be seen.

Human genes in pig sperm for organ donors
Oct. 21, 2002 at 5:30 PM

MILAN, Italy, Oct. 21 (UPI) — Italian scientists said Monday by piggybacking human genes in pig sperm they have created swine that someday might help serve as life-saving donors for organ transplants to humans.
These new pigs have tissues better able to resist the human body’s immune rejection system. The research team hopes this will help improve “xenotransplantation,” or organ transfer across species.

Not a new release as it is dated 2002, but this is the first I’ve seen of it.

For the most part, scientists genetically modify animals by injecting DNA into eggs right after they are fertilized, a tricky and expensive operation. While this “microinjection” technique is fairly successful for mice, “it’s about 10 times less effective for livestock than mice,” Wall said. He suspects one reason is because scientists have bred lab mice to produce hardier eggs on average than livestock.

Since sperm are designed to deliver their DNA into eggs, Lavitrano and colleagues tried using sperm as gene carriers. In 1989, they reported sperm could absorb foreign DNA into specific places in their chromosomes.

I note that there is significant differences in how a given technique works between species, such as those mice being easier for the microinjection standard technique. This implies that any given species might have an easier time with any particular form of gene mixing.

But some other folks had trouble with reproducing their work, so they continued to work on the technique.

After much tinkering, Lavitrano said her team has now optimized the technique. “We’ve discovered what to do — how much DNA to use, when to give it, for how long, and in what condition,” she explained. “We do not need any of the expensive equipment, microscopes or anything, that you need with microinjection.”

Instead of extracting sperm cells from pigs or using frozen sperm, Lavitrano’s team coaxed two male pigs with healthy sperm to ejaculate. Such sperm are more mature, she said, and frozen sperm cell membranes are damaged. Unlike sperm extraction techniques, where pigs are then killed, Lavitrano added “we can use ejaculate for a long time.”

The semen fluid was washed off the sperm, since it protects them from absorbing DNA. The bottles of cleaned sperm then simply had DNA mixed with them for two hours, with scientists flipping the flasks upside-down every 20 minutes to keep the sperm from settling.

So the seminal fluid is the ‘barrier’ between a sperm cell and DNA absorption. Are all animal seminal fluids equally effective? Do all sperm react the same, even to other species seminal mix? Where I’m going with this is pretty simple. In many cases ‘in the wild’ there are cross species matings. Now mostly those do not produce viable offspring, some often they do. A genetic 50:50 mix of the nuclear DNA of the two species. But this method raises another potential pathway. DNA absorption.

So lets say a hypothetical rabbit hops onto an interested cat ( happens rather often… and perhaps occasionally with some result… look up cabbits ) and goes for it. Now even if nothing happens, lets say the sperm hang around for ‘a while’ and during that time a tomcat mates as well. Now there is the potential for some of the DNA from the rabbit to be absorbed into the cat sperm. Likely? Absolutely not or we would be up to our eyes in a variety of bizarre critters. But not impossible either. And that which is very unlikely but not impossible will happen with enough trials…

Perhaps this is how some of the unexpected bits of one type of DNA end up in seemingly too distant other species. As I’ve pointed out many times, the “species barrier” is more of a “species strong suggestion”; and this shows that DNA absorption can happen at different points in the process. Not just via a virus picking up some environmental DNA and hauling it along ( known to happen ) but also potentially via other cells ‘sharing’ more than we expect from a perfect world ( as the world is not perfect ).

The scientists used the gene for human decay accelerating factor, or hDAF, a protein found on cell surfaces that protects cells from their body’s at-times misguided immune system. When eggs were fertilized with these modified sperm in vitro and implanted into mothers, 57 percent of the 93 piglets born had hDAF in their hearts, lungs, kidneys, ears and tails. DNA injection would have only led to a 0.5 to 4 percent success rate, Lavitrano said.

So with a wash, the rate of absorption is 57/93 or 61%. That’s impressively high. So if things are not ideal, does that drop to 1/1000 or 1/10000 or 1/1,000,000?

I strongly doubt it is perfect at 0/100,ooo,ooo …

In related news, we have somatic cells swapping DNA around.

Pig-human chimeras contain cell surprise

13:42 13 January 2004 by Gaia Vince

Pigs grown from fetuses into which human stem cells were injected have surprised scientists by having cells in which the DNA from the two species is mixed at the most intimate level.

It is the first time such fused cells have been seen in living creatures. The discovery could have serious implications for xenotransplantation – the use of animal tissue and organs in humans – and even the origin of diseases such as HIV.

The adult pigs that had received human stem cells as fetuses were found to have pig cells, human cells and the hybrid cells in their blood and organs.

“What we found was completely unexpected. We found that the human and pig cells had totally fused in the animals’ bodies,” said Jeffrey Platt, director of the Mayo Clinic Transplantation Biology Program.

A bit vague on some points, then again they likely don’t know what all happened. What was the chromosome number of the mixed cells? Was it a 50:50 mix, or just a few genes jumped over the fence?

The hybrid cells had both human and pig surface markers. But, most surprisingly, the hybrid cell nuclei were found to have chromosomal DNA that contained both human and pig genes. The researchers found that about 60 per cent of the animals’ non-pig cells were hybrids, with the remainder being fully human.

Importantly, the team also found that porcine endogenous retrovirus (PERV), which is present in almost all pigs, was also present in the hybrid cells. Previous laboratory work has shown that while PERVs in pig cells cannot infect human cells, those in hybrid cells can. The discovery therefore suggests a serious potential problem for xenotransplantation.

So in over 1/2 the cases of non-pig cells, the human line had fully blended with the pig line and made hybrid cells. (At least for the particular genetic marker they measured.) That’s a rather high rate. Also consider that many twins are from one fertilized egg splitting into two at an early stage of division. It is quite possible for one of those ‘hybrid cell’ clusters to be split off into a distinct embryo and not just a minor part of a chimera blend of cells. Can you say “That’s gonna be a problem”?

There is also that ‘issue’ with a pig-only virus making the leap to the hybrid cells (and then to human cells after a bit of mutation?)

This sort of thing is also why I’m against broad introduction of GMO foods. The GMO is typically made using techniques that can cause a variety of unexpected genetic changes, then ‘survivors’ are propagated (baggage and all). They use a virus genome to drag the DNA into the cells, so that package is floating around in the mix. Then there’s a ‘locked on’ codon to make sure the trait is expressed no matter what. My question has just been “What happens when digestion breaks down parts of those cells, and all those bits of GMO Machinery are sloshing around in the gut?” What bacteria or other cells does it start changing and inserting things into? No, not 100% of the time. Maybe only 1 in 100,000. But if 1,000,000,000 people are eating that stuff, you have 10,000 ‘with issues’… We simply do not know what will happen. (There have been some changes shown in bacteria and in some gut linings some times, so something happens.) Personally, I’d rather not have bits of ‘BTtoxin making genes’ floating around in my gut for bacteria or my gut lining cells to pick up, since it is shown to be an allergen.

In Conclusion

Nature is not very ‘tidy’ about genetic material. At the bacterial level, it’s a flat out free for all with plasmids moving chunks of DNA around between all sorts of species. Now we’re seeing that even at the level of mammal cells some amount of DNA swapping happens, and in a variety of contexts.

In some ways we really “are what we eat” and it really is true that all life is connected. I’d just rather not be too connected to things without my approval.

Nature. 2014 Oct 9;514(7521):181-6. doi: 10.1038/nature13793. Epub 2014 Sep 17.

Artificial sweeteners induce glucose intolerance by altering the gut microbiota.

Suez J1, Korem T2, Zeevi D2, Zilberman-Schapira G3, Thaiss CA1, Maza O1, Israeli D4, Zmora N5, Gilad S6, Weinberger A7, Kuperman Y8, Harmelin A8, Kolodkin-Gal I9, Shapiro H1, Halpern Z10, Segal E7, Elinav E1.
Author information

Non-caloric artificial sweeteners (NAS) are among the most widely used food additives worldwide, regularly consumed by lean and obese individuals alike. NAS consumption is considered safe and beneficial owing to their low caloric content, yet supporting scientific data remain sparse and controversial. Here we demonstrate that consumption of commonly used NAS formulations drives the development of glucose intolerance through induction of compositional and functional alterations to the intestinal microbiota. These NAS-mediated deleterious metabolic effects are abrogated by antibiotic treatment, and are fully transferrable to germ-free mice upon faecal transplantation of microbiota configurations from NAS-consuming mice, or of microbiota anaerobically incubated in the presence of NAS. We identify NAS-altered microbial metabolic pathways that are linked to host susceptibility to metabolic disease, and demonstrate similar NAS-induced dysbiosis and glucose intolerance in healthy human subjects. Collectively, our results link NAS consumption, dysbiosis and metabolic abnormalities, thereby calling for a reassessment of massive NAS usage.

So here we have artificial sweeteners changing our gut bacteria in such a way that they induce us to become fatter (and drink more artificial sweetener soda…); and transferring those bacteria to a new host makes it fatter too.

So why the “obesity epidemic” and the “diabetes epidemic”? Perhaps the millions of tons of artificial sweetener used in this country and the way it changes our metabolism and that of our bacterial content. (Burger and fries not so much the problem.)

Is this via a genetic mechanism? Well, likely not via any direct DNA change, but epigenetics might well enter into it. At some point all life chemical actions are genetic driven via protein & RNA synthesis, so it will be turning on some genes or turning off others. Then that pattern can be transplanted with the bacterial population.

The point of all this isn’t just that you ought to drop the artificial sweeteners from your diet. It is to point out that life adapts. In many ways, and often. Any change you make has a large potential impact, so watch such changes closely and do not accept them lightly. Also realize that in the wild, all sorts of changes are going on all the time, and life adapts. Not just by point mutations in a DNA strand (that are actually one of the slower ways to adapt) but via many kinds of DNA swapping ( the fastest being that every species with two sexes swaps DNA at every new individual. We are all a ‘new mix’ so that diseases have trouble ‘locking on’ to how to make us sick.) In that context, the idea that some DNA might move between species via sperm picking it up after a cross species dalliance, or via interspecies hybrids, is not “alien” or “against nature”. It is right in line with the desire of cells to ‘mix up the genes’ and see what happens or see if they can find a ‘new mix’ that stops some infections or parasites.

So be careful what you eat and who you hang around with… ( Gee, I think my Mom said that…) there’s a whole lot of ‘sharing’ going on.

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About E.M.Smith

A technical managerial sort interested in things from Stonehenge to computer science. My present "hot buttons' are the mythology of Climate Change and ancient metrology; but things change...
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6 Responses to Gene Swapping via Sperm Absorption of DNA

  1. p.g.sharrow says:

    @EMSmith;”In some ways we really “are what we eat” and it really is true that all life is connected. I’d just rather not be too connected to things without my approval.”

    ;-) At times you can learn too much for comfort. To get more connected than necessary is not a good idea.

    It has been pointed out many times that those that consume diets low in sweets and high in protein and fats have little trouble with obesity and diabetes. The taste of sweet in your mouth sets off a cascade of hormonal changes from your brain to direct metabolism changes in your body. NAS consumption causes the bad effects of sugar without the benefits of increased nutrients. Your body is flooded with insulin that is not needed and over time detrimental and makes fat out of proteins to save the calories from the “sugar” that it thinks it is consuming. With the lack of real calories you are in starvation mode that demands more food, save fat and be less active. You just get more fat and lazy. It says on the NAS packaging, Use ONLY if you must limit your consumption of sugar. Humans were not made to exist on sweets. Sweets were a very rare treat before the 1800s and the creation of the sugar industry. NAS is even worse then sugar for extended consumption. pg

  2. DonM says:

    I like the Cabbit link … would not have guessed that it could happen or that anyone would seriously advocate its possibility.

    My great grandmother had a litter of cats living under her house at one point. They appeared (to me as a 5 year old) to have their back legs on backward … they hopped. I had always assumed that the cats were just malformed (and maybe that’s all that is was). Over the years when I have told others about them I would say that they were genetic misfits … “poor little kittens that made strained little hops to get around kind like a mix between a cat and a rabbit”. Now that I think about it again, it seems very odd that the entire litter would have the exact same malformation caused by a genetic problem.

    But all in all, until I see the DNA test confirmation, I can’t buy into it (although I would hope for confirmation).

  3. Power Grab says:

    I can’t find it now, but I found an article that said that the most common NAS are antibiotic. So it’s not surprising that they alter the gut flora. I remember seeing an article that had a quote from a dentist, encouraging people to eat plenty of NAS because they would kill germs in the mouth.

    So now that they’re finding out which flora are plentiful in lean people (vs in obese people), it’s starting to fit together.

  4. p.g.sharrow says:

    Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion
    Some new information on Human genenetics;
    “Still, this genetic change is unlikely to fully explain human smarts, Huttner said. Both humans and Neanderthals had large brains, but human’s unique intelligence may have more to do with how brain cells form and prune neural networks over time, he said.

    Though the gene creates many more neurons to work with, “how those neurons wire up to allow us to fly to the moon, but not the Neanderthal, that is more likely to be a function of genes expressed in neurons,” as opposed to genes expressed in progenitor cells, Huttner told Live Science.”
    “Evolutionary expansion of the human neocortex reflects increased amplification of basal progenitors in the subventricular zone, producing more neurons during fetal corticogenesis. Here, we analyze the transcriptomes of distinct progenitor subpopulations isolated by a cell polarity-based approach from developing mouse and human neocortex. We identify 56 genes preferentially expressed in human apical and basal radial glia that lack mouse orthologs. Among these, ARHGAP11B has the highest degree of radial glia-specific expression. ARHGAP11B arose from partial duplication of the Rho GTPase-activating-protein–encoding ARHGAP11A on the human lineage after separation from the chimpanzee lineage. Expression of ARHGAP11B in embryonic mouse neocortex promotes basal progenitor generation and self-renewal, and can increase cortical plate area and induce gyrification. Hence, ARHGAP11B may have contributed to evolutionary expansion of human neocortex.”

    It would appear that humanity may be due to a genetic copying mistake or maybe a bit of GMO fiddling ;-) pg

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