I’m not talking about million of years old dinosaurs re a “Jurrasic Park” type reconstruction, but rather nearer term things like mammoths, saber tooth tigers, giant sloths, moas etc. that are thousands of years old where DNA may still be readable. Legalities aside, is it even within the realm of possibility to do this with current or near term genetic bio-technology or is it still science fiction?
I suspect that one difficulty in actually doing this lies in mitochondrial DNA. Juassic Park did not, to my remembrance, address the issue of putting replicated mitochonrial DNA into the host egg cell. I don’t know how we’d be able to do that.
There’s more to this than just the DNA in the cell nucleus.
And that just pretty much exhausts what little I do think I understand about the process. Others will have to continue and/or shoot down what I just wrote.
DNA degrades pretty quickly. While we’ve found segments of DNA in fossils, I don’t believe that any full genomes exist from fossil evidence. Without that, there’s no hope.
The one possibility is from mammoths that were frozen and found more of less intact. Even there the DNA is in less good shape than many hoped.
Here’s a 2002 Salon.com interview with a science writer who wrote a book about it.
I can’t find any evidence that he’s gotten any farther since then.
And neither did Hwang Woo-Suk.
Here’s an article which discusses some of the obstacles to reconstructing a mammoth.
It would be possible in principle to use mammoth DNA to reconstruct the animal. The main problem is that available nuclear DNA is too broken to use as is. Even when tissue is frozen DNA begins to break down. If a specimen is found with exceptional preservation, that might make it somewhat easier.
It may be possible sometime in the future to sequence the full mammoth genome and “patch” the broken bits together, or even splice mammoth genes into the genome of a living elephant species. But AFAIK this kind of capability is still a fair bit away.
Probably not that much of a problem. The way it would probably be done, if nuclear mammoth DNA were available, would be to take the nucleus out of an elephant’s ovum and replace it with mammoth nuclear DNA. This is a standard technique used in cloning. The resulting animal would have mammoth nuclear DNA and elephant mitochondrial DNA, but the nuclear genome is far more important in generating the appearance of the animal.
Do we really know this? How far has anyone actually gone in allowing a chimeric (different species mitochondrial DNA) embryo to develop into a viable individual. I understood that there were some serious concerns regarding energy production and control being matched with the nuclear DNA?
Si
Never mind mammoths, how about something more recently extinct. What about dodos? Do the few fragments of dodo that were preserved contain enough usable DNA for cloning? Passenger pigeons? Tasmanian tigers?
By the way, I’m sure there must be a reason, but if you can recover a nucleus from a preserved specimen, and place it into a host cell, why can’t you do the same with mitochondria?
Is there any fundamental reason why it can’t be done? Or is it the fact that you’d have to replace several thousand of them?
Because intra-cellular nanosurgery isn’t that developed yet. Transplanting nucleus is recent and huge success - and still it fails in most of cases. Transplanting a lot of small organelles is impossible at present level of technology.
You are not going to recover an entire nucleus - you will need to recover enough DNA to reconstruct the chromosomes, then make a nucleus (which no-one has attempted yet), and then insert that into a currently working cell - and this is why you can’t replace the mitochondria as well. The internal cell mechanisms need to be running - you can’t shut down the cell, swap mitochondria and then restart it.
We are a long way off. Some current research into completely artificial bacteria will move this along, but it is in very early stages.
Si
It’s been done with the Banteng, and endangered species of wild cattle, using the ovum of a domestic cow. Of course, these animals are in the same genus, while mammoths and elephants are more distantly related.
One of the two banteng calves had to be euthanized because it was larger than normal (“large calf syndrome”), but this is a problem with cloned animals in general, and is not necessarily related to the interspecific nature of the clone. I am not sure what the status of the second calf is.
While there are certainly obstacles, the idea is possible in principle. Hpwever, IMHO actually doing it is probably more than a decade off, but less than a century.
In addition, because of their primary function (energy conversion via oxidative phosphorylation and production of enzyme ATP synthase to bind proteins to ADP to create ATP) they’re highly prone to oxidative damage, which is only countered by importing proteins produced by the cell nucleus. Without a constant stream of support and maintenance of a regulated electrochemical gradient that allows correct proton balance they tend to break down from oxidative stress–literally “burning up” or oxidizing via their own energy production mechanisms–and thus don’t survive outside of functional cell environments. The mitochondria (and chloroplasts in plants and some alge) should really be considered obligate endosymbiots (according to the now widely accepted endosymbiotic hypothesis) derived from prokaryotic proteobacteria and cyanobacteria which “gave up” certain protein produciton functions required for their own maintenance in favor of highly specialized energy production. It’s quite possible that some of the apparently non-functional (or at least, non-coding) nuclear DNA also plays some function in mitochondrial support.
The advantage of this (from a gene-centric point of view) is that they and the genes contained within get a free ride from the host cell, so that instead of directly competing with other organisms they are the underlying energy production of all. However, it isn’t clear how such a cooperative system came to occur; there are many secondary obligate endosymbiots which feed from waste products of their hosts, but few if any that are literally tied into the genome of the host cell and co-evolve directly with it. The steps necessary for such a joining seem so almost infinitely unlikely that some argue it as a case for the low probability of eukaryotic type life (and thus multi-cellular, specialized organisms) to emerge anywhere else, and others claim it as evidence of a divine architect. However, we know that this type of endosymbiosis has occurred at least twice (once in plants, one in animals) and possibly more times. Although we don’t and probably will never know the mechanism by which the necessary genes came to be transferred from independent proto-mitochondria to eukaryotic nuclear genomes per se, further research in proviral- and prophage-facilitated horizontal gene transfer may offer a viable hypothesis into the particulars of such a conversion.
Meanwhile, mithchondria are directly tied into the operation of the host cell, and indeed, mitochondria could be said to regulate and control the host survival to their own “interests”. (There is much speculation that cell division, growth, and aging are all strongly influenced or directly controlled by operations within cellular mitochondria.) Because mitochondrial mtDNA mutate pretty quickly (compared to most nuclear DNA) a mismatch between mtDNA and host DNA may cause a number of development and functional problems. This may even be a problem within allopatric and peripatric distinctions within species (as well as undesirable mutations in mtDNA and chromosomal DNA) that lead to chronic mitochondrial dysfunctions, many of which are latent (and therefore can be widely dispersed within a viable population) until mature or advanced age. Many of the chronic disorders of aging are probably at least partially the result of mitochondrial dysfunction or decline of efficiency of the Krebs cycle within mitochondria.
As Colibri notes, attempts at chimeral transfer of genomes into even an ovum from closely related species or animals within species often results in developmental problems that are still not well understood but widely thought to be related to mitochondrial function. Our understanding of mitochondrial function is still quite limited–indeed, until the late 'Thirties the understanding of energy production in cells was not well understood, and it wasn’t until the mid-'Seventies (I think) before the role of mitochondria in energy production and regulation per chemoiosmotic theory was even accepted to be central. The real functions of mitochondria are still being argued among molecular biologists, and because it is very difficult to observe them “in action” (having to function within a living cell, and on a scale below optical observation) it is a matter of proposing unlikely hypotheses based upon a still fairly crude ability model protein interactions and throwing them against the wall until something sticks.
So taking nuclear genes from a long-extinct species (even assuming you can sequence them back together in some semblance of correct order) is not likely to give you a viable animal. And collecting useful fossil mtDNA is like trying to solve a 1000 piece jigsaw puzzle with only fifty pieces at a time. I suspect it’ll be well over a decade–probably more like three or four at a minimum–before we can “manufacture” co-functional mitochondria to work with even a complete nuclear genome, much less a fragmentary fossil one. This will require significant advances in the technology of gene transfer, gene sequencing, and regulation of embriotic development.
Stranger
There is a Texan oil man who’s hoping to open a prehistoric park, filled with cloned animals like mammoths. He’s not had much luck in getting any DNA, however, as the academics find the best specimens and won’t share. :mad:
I remember reading in a science magazine back in the 1980s of someone doing some experiments with animal hides that had been preserved in the 1800s and being able to induce cell division in the skin cells. Haven’t heard any more about it, so that might mean research was dropped because cloning (at that time) was impossible, or it might mean that there was problems with the research.
Quasi-related technique: take mammoth sperm and use it to knock up an African elephant.
Didn’t work, unsurprisingly.
Thanks Colibri. I sort of agree with the timescales.
While I have doubts about whether useful stem cell therapies can come from human/animal chimeric clones, I do believe that the research now is useful for developing the techniques to manipulate stem cells and create therapies, without relying on human eggs. Couple that with other research into forcing donor cells back into stem cells and 3-D cell printers, and we may have some exciting new options in 10 years time.
Si