How to make a Mammoth

By Peter Dearden 19/04/2015 2


Peter K Dearden.
You might have heard that Mammoths are pretty close to being de-extinctioned. Reports were all over the internet after a geneticist at Harvard University, Prof George Church, explained that they had inserted Mammoth DNA into elephant cells in culture. Soon, it was suggested, we would be riding mammoths to work, or using them as hairy guard dogs. But are we really that close?

MammothVsMastodon

A mammoth (left) and a mastodon (right). Hairy right? (By Dantheman9758 at the English language Wikipedia [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], from Wikimedia Commons)

Mammoths came as lots of species, most of which appear to have died out at the end of the last ice-age (about 10,000 years ago). They came in a range of sizes, from huge to extremely massive, and also a range of hairiness. They also lived, helpfully, in cold places, and their frozen bodies have been found melting out of the northern permafrost.

Lyuba
Luba, a defrosted baby Mammoth from the Chicago Field Museum. (By Matt Howry from Ardmore, OK, USA (IMG2718 Uploaded by FunkMonk) [CC BY 2.0 (http://creativecommons.org/licenses/by/2.0)], via Wikimedia Commons.)

These frozen corpses have given us the opportunity to extract mammoth DNA, and sequence it; indeed there is a mammoth genome project  that aims to sequence the whole genome of these extinct beasties.
So if we have the whole genome of an animal that can be reconstructed, surely we can make one. The genome of an organism contains, we think, all the information that is required to build and run that organism. If that is true, then we should be able to put those instructions into a cell and -et voila- mammoth.
Prof Church’s work doesn’t appear to be aiming in this direction. His work, which is as yet unpublished, seems to be about finding out how mammoth protein differ in their function from elephant ones, and how they make mammoths and elephants different. This is cool right? Its a nice idea to resurrect the function of a gene that died out 10,000 years ago. One might point out that studies of small (microevolutionary) changes between species indicates that many of these are due to changes in gene regulation rather than gene function (look up Prof Sean Carroll’s papers), so these experiments might not tell us much about what makes a mammoth.

Can we go from having a mammoth genome to having a living, trumpeting mammoth? There are two key problems:-
1) Animal genomes are structured in three dimensions. While we can make the sequence of a mammoth genome, we can’t structure the genome the way that a mammoth did. We don’t have tools to help us understand how it was structured in a mammoth, or to make any bit of DNA a structure we want. This structure is not trivial, as we are beginning to understand that the 3D structure of the genome affects which genes are turned on and which are turned off.
2) Eggs. Animal eggs are not just a random cell that divides to kick off embryogenesis. Eggs are structured, with information placed maternally into the egg that helps direct embryogenesis. Even the point that the sperm enters the egg is used by some animals to direct the early phases of development. All of that positional information from mammoth eggs is lost in the depths of time.
But perhaps we could use elephant eggs! Lets hoick out the genome from an elephant egg, and bung in a mammoth one, and -et voila- baby mammoth. Well o.k., might be worth a try, but my group, and others (including the awesome Dr Peter Pfeffer from AgResearch), have shown that the early events in embryogenesis evolve pretty rapidly. This means the structure and information encoded in mammoth eggs may not be the same as elephants. We might need a mammoth mum to make a mammoth egg, before we can resurrect the species.

The age old question of which came first, the mammoth or the egg, is going to be a problem for resurrecting extinct species. The question, is however, a neat one, if you are a developmental biologist*. Eggs are structures produced by genetics, development and ancestry. Eggs themselves have a evolutionary history, shaped by the evolution and development of the forebears of a particular animal. It may be that the tricky bit of resurrecting species is not getting the genome, but producing an egg.

 

 

* the correct evo devo answer to ‘which came first the chicken or the egg’ is theropod dinosaurs.


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