Thursday, February 3, 2011

Is A Cloned Mammoth Half a Decade Away?

ResearchBlogging.org
The concept of cloning an extinct animal is no longer considered science fiction in the scientific community, but the problems associated with accomplishing this task seem to only increase with our understanding of development. One of the real problems with cloning an extinct creature isn’t just getting the DNA, but having a proper surrogate for the embryos development. As recent advances in genomics have made clear, shoving DNA into a cell is unlikely to accomplish much of anything.  The genome has to interact with a number of maternal genes (genes released by the mother) as well as regulatory networks that are initiated during fertilization.  So even if you had the DNA of an extinct animal, you probably need a close relative to act a surrogate and provide the appropriate genetic regulation.

This bodes poorly for dinosaurs, which never had much of a chance to begin with since DNA doesn’t seem to survive past a few hundred thousand years, even in the best conditions.  DNA has been recovered from prehistoric animals like saber-toothed cats and giant sloths, as well as recently extinct animals such as the Tasmanian wolf, but these animals have no close relatives alive today.  Other prehistoric animals, such as extinct bison or horses, or the massive auroch cows, do have close relatives and may be feasible to clone (they may very well be the first extinct animals cloned), but aren’t quite as exciting as a dinosaur.  Neanderthals have a genome and a close relative, but that opens up a whole can of ethical issues…


This is why my money is on the wooly mammoth



The mammoth genome has already been sequenced, and it is clearly a very close relative to living elephants.  In fact, it appears more closely related to Asian elephants than living African elephants are.  In theory, one could synthetically reconstruct the entire genome of the mammoth, stick it into an egg, and place the egg into a female elephant.  Unfortunately, while last year did mark the creation of the first synthetic life-form (Gibson et al. 2010), that was a simplified bacteria with a little over 1 million DNA base pairs in its genome.  The mammoth, by contrast, has 3-4 billion base pairs, making a synthetic genome too costly, at least for now…

Instead of synthetically engineering a genome, the other possibility would be to get good eggs and/or sperm from a frozen mammoth.  Several research teams have been trying this for over a decade, but in news articles covered by CNN and the Japanese Daily Yomiuri, scientists collaborating from Japan, Russia, and the US report the collection of promising tissues last summer.  There are large numbers of them frozen across northern Europe, Asia, and North America, and with the warming trends in the arctic, more and more mammoths are being discovered every year.  They also have perfected a technique to extract nuclei from frozen eggs without damaging them.

According to these news articles, the team is hoping to have it done in five to six years. I have a $20 bet riding on the cloning of a mammoth within the next ten years.  Here’s hoping.


Works Cited:

Gibson DG, Glass JI, Lartigue C, Noskov VN, Chuang RY, Algire MA, Benders GA, Montague MG, Ma L, Moodie MM, Merryman C, Vashee S, Krishnakumar R, Assad-Garcia N, Andrews-Pfannkoch C, Denisova EA, Young L, Qi ZQ, Segall-Shapiro TH, Calvey CH, Parmar PP, Hutchison CA 3rd, Smith HO, & Venter JC (2010). Creation of a bacterial cell controlled by a chemically synthesized genome. Science (New York, N.Y.), 329 (5987), 52-6 PMID: 20488990

2 comments:

  1. Hello Dave,

    I must say that this blog post was quite a fascinating read for me! I love the prospect of reviving species ala Jurassic Park. I do have a few questions related to biological processes and science behind mammoth cloning, however:

    (1) What types of cells are required to be extracted from Mammoth remains to produce a viable mammoth zygote?
    (2) Does the potential cellular degradation present in 10,000-year-old mammoth DNA affect how well the mammoth embryo/organism might develop and grow? What are some of the ways scientists can distinguish between real mutations present in the organism at the time of expiration vs. cellular degradation?
    (3) Has the technique developed by researchers to extract nuclei from 16-year-old frozen mice been validated for any other species/length of time? Is there any reason to assume that the effort to co-opt this technique for use on mammoth DNA will be successful at all?

    Thanks for the article once again Dave! You keep on writing them and I’ll keep on reading.

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  2. Great Questions:

    (1) I know scientists have considered both using gametes (sperm/eggs) and somatic (body tissue) cells for cloning. The problem with somatic cells is that DNA in these cells are sometimes modified in a process called epigenetics (I hope to talk more about epigenetics in the future, but until then you can always Wikipedia it). These modification of the DNA might complicate the creation of a viable zygote. Of course, cloning from somatic tissue generally works with enough trial and error; that's how Dolly the Sheep was cloned.

    (2) Degradation of DNA could definitely be a problem, and I can't imagine a straightforward way of determining genuine mutations from degradation. Because their are a number of mammoth genomes, scientists have a growing idea of how much genetic variation exist between individuals (there was a paper a while back showing that some mammoths had the mutation for blonde fur!). So if their sample has an unusually high amount of genetic variation, that might help them determine that a specific sample is degraded.

    (3) I don't think the nuclei technique has been tried on anything but a mouse. To an extent, a mammal cell is a mammal cell, so it should be widely applicable, but the age difference may be a problem.

    Overall, I think the take home message of these answers is that there are a lot of possible pitfalls still, so we might not get our mammoth as soon as we hope. Thanks for the questions, and let's hope I win that bet...

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