Cloning Mammoths

Anonym Feigling writes "For your consideration... An article over at the New Zealand Herald discusses some of the challenges a japanes team faces as it attemps to develop a system to create a clone from 20,000 year-old mammoth tissue samples discovered in Siberia. It seems to me that shortly after death, any animal's/plant's "cellular repair mechanisms" (for the lack of a better...) will fail, and thus the probability of finding a single cell with perfectly intact DNA from which to create a clone is pretty well zero. Interesting stuff, but it seems that practical considerations (think code rot) would make it difficult."

Comments

Code rot probably not the best analogy

[Quixotic Raindrop]

I get what you're saying, but code doesn't really "rot" in the same way that living cells do. I believe that if there are any intact cells they'd be lucky, but you don't need an intact cell to extract a DNA sample.

Re:Code rot probably not the best analogy

[bcrowell]

They had a pretty hard time with the neanderthal femur they found a while back.
AFAIK, they only analyzed the mitochondrial DNA (mtDNA) from the neanderthal sample, not the nuclear DNA that codes for proteins. They also did Oetzi, the 5000-year-old man they found in an alpine glacier.

mtDNA is only inherited from your mother, and is useful as a clock because it's not strongly selected for. There's also a lot more mtDNA in a cell than nuclear DNA, which makes it easier to recover mtDNA from an old sample than it is to recover nuclear DNA. Even though mtDNA is easier than nuclear DNA, they didn't even try to recover the complete mtDNA genome on these samples -- they just used them statistically, as clocks.

The neanderthal DNA showed that our last common ancestor with the neanderthals was 500,000 years ago, which implies that we're separate species, i.e., it supports the total replacement model (we lived alongside neanderthals and Homo erectuses for a long time, and then they went extinct) rather than the multiregional model (where H sapiens arose through worldwide interbreeding with other archaic hominids).

Oetzi's mtDNA was virtually indistinguishable from the mtDNA of the people who currently inhabit the region.

Re:Code rot probably not the best analogy

[Sgt York]

Getting intact full DNA from a living cell, prepared freshly is a challenge. And it does "rot", just like living cells. It's a molecule, and anything that will decay a cell will take the DNA in that cell along with it.

There is also molecular decay, independent of decomposition from microorganisms. DNA is subject to autocatalytic acidic hydrolysis; that is, in any solution with a pH lower that about 6 or 7, it will break itself up into little chunks. Most tissues become quite acidic after death. The DNA is still there, kinda, but it's broken up into little bits.

You don't need intact cells to get DNA, that is true. But to clone, you need a full genome, intact. Each chromosome needs to be a full sequence. For other applications, busted up DNA is fine. You can sequence, look for similarities, etc. But to clone, you need the whole thing, all in it's correct pieces.

Would you want to?

[Creepy Crawler]

Knowing how much just plain elephants eat and destroy, would we want double-sized hairy elephant?

Scitentifically, that's cool. But ask yourself: Why did they die out?

fp

Re:Would you want to?

[mess31173]

But ask yourself: Why did they die out?

Odds are, the reason that they died out, along with around 70 other species of giant mammals around that time is us. Although some claim it could be weather. The article addresses both possiabilities.

Because... Re:Would you want to?

[WolfWithoutAClause]

Because, they reproduce slowly, and they're finger-lickin good ;-)

(Mammoths died out only 5000-10000 years ago- they definitely would have had run ins with our ancestors.)

Don't always need an intact DNA

[WolfWithoutAClause]

You can probably take two different, damaged copies of the DNA and PCR amplify them up, and generate a protein to stick them back together in the right way. It would be fiddly as hell, but in principle you can do it perfectly.

Once you have an intact copy of the DNA you can clone with it.

Alternatively, take the fragments of mammoth DNA and sequence them, then run the sequenced DNA through a DNA 'printer'. These machines exist- you feed in the DNA sequence on CD rom and out pops the actual DNA you want. It might take years or even decades(!) but it would certainly be possible in principle.

Re:Don't always need an intact DNA

[TCQuad]

Three considerations:

1) In order to PCR amplify something, you need primers which bind to the target areas and begin the replication. The primers need to have a known sequence, and we don't really know the mammoth genome, so we don't know what we're looking to amplify.

2) Mammoths have multiple chromosomes, so this isn't a one-step process. You'd need to repeatedly amplify section after section on each chromosome. Not impossible (per se), but not really feasible with todays technology due to:

3) Good day, high wind, Herculase (a PCR enzyme for long targets) can get 48,000 base pairs in one cycle with reasonable accuracy. The E. coli genome is 5.4 million base pairs. To PCR the entire E. coli genome you'd need to repeat the process 113 times to get the entire genome; if you're lucky enough to get the max every time, it'd take a lot of complex stitching to get it done. Of course, a mammoth is a lot bigger and more complex than a bacterium. The Fugu (pufferfish) genome is ~100 times bigger than E. coli (300 million), humans ~1000 times (3-4 billion). You can see the difficulty in using PCR for this type of application.

You are right, in principle, that you should be able to do all of these (eventually) but you also have to remember that each of these processes (not to mention troubleshooting!) takes materials (original DNA) in significant quantities. If we don't have a herd of mammoths, we probably don't have enough for what you suggest.

Not can do, but should do?

[jpsst34]

Here comes the barrage of "proving they can do it without considering if they should do it" posts. Well, here's a good reason why I'd want to clone mammoths: They'd make great pets. Kind of like Porno for Pyros would. Except that their prohibitive size would mean you'd probably have to hire a poopsmith just to clean up after the fucker!