Friday 24 April 2015

Mammoth de-exinction: not good for elephants, not good for science?

Two woolly mammoths (Mammuthus primigenius) have had their genomes sequenced by a team led by the Swedish Museum of Natural History: Complete Genomes Reveal Signatures of Demographic and Genetic Declines in the Woolly Mammoth. The BBC story included coverage of the Long Now Foundation and their plans for de-extinction via genetic-rescue; "to produce new mammoths... repopulate [] tundra and boreal forest in Eurasia and North America", but "not to make perfect copies of extinct woolly mammoths, but to focus on the mammoth adaptations needed for Asian elephants to live in the cold climate of the tundra".

The Mammoth genome story is likely to be big news and I think that is unfortunate, not just for the elephants that are going to get fur coats and be shipped off to cooler climes, but also for the perception of science and scientists. It perpetuates the mad-scientist image and people will inevitably think of films like Jurassic Park. I find it difficult to think of reasons why we would actually need/want to adapt Asian elephants (why not African elephants too) for modern Siberia. Is anyone honestly going to use genome editing on a large scale to make a hairy elephant so it can live in the cold? This kind of coverage is not especially good for science, but it is probably great for your rating on Google!

The mammoth genomes: The two genomes are separated by 40,000 years; the first was from a 44,800 year old (Late Pleistocene) juvenile found in Siberia, the second from a 4300 year old molar taken from a Mammoth that lived in probably the last extant population on Wrangel Island.

Pretty standard library construction with the addition of a UNG step to remove uracil bases (resulting from cytosine deamination) that reduced C>T artefact's. Genomes were aligned to an (unpublished) 7x Sanger-seq African elephant (Loxodonta africana) genome, LoxAfr4. Alignment to the reference showed differences in the average length of perfectly mapping reads, 55bp and 69bp for the Siberian and Wrangel Island individuals respectively. Population size was estimated by measuring the density of heterozygous sites in the genomes, the authors are explicit in stating that there analyses is probabilistic and they "always quote a range of uncertainty". This analysis suggested two population bottlenecks; the first 280,000 years ago, and the second more recently 12,500 years ago at the start of the Holocene. This second indicated a probable significant drop in mammoth diversity in the time just before extinction, possibly due to in-breeding. The Wrangel Island sample had large regions termed "runs of homozygosity", about   23%  of the genome.

There is a possibility that more genomes are coming as the group sequenced DNA from 10 individuals to find one good one, and are on the hunt for more to better understand mammoth diversity and the reasons behind extinction. 

De-extinction: Beth Shapiro at UCSC is author of the book How to Clone a Mammoth and she'll be doing a talk and book signing at Oxford University Museum of Natural History Tuesday, 19 May 2015 at 6PM, she previously published research on the museum’s Dodo.
In How to Clone a Mammoth she discusses the challenges both scientific and ethical that make de-extinction tough, "I question if it's something we should do at all"! Cloning is likely to be impossible so we'll have to result to genome editing or recombineering to get extinct species DNA into their closest modern relatives.

We need good science stories to hook news broadcasters in whichever media we can, but with impact being one of the metrics many PIs are judged on nowadays it might be too tempting to spin a story a little too hard. Chris Mason's recent Cell paper on New York's subway metagenome got some tough criticism for over-playing the levels of Anthrax and Plague. Although the paper itself is pretty clear about the realities of what the data show.

I don't imagine the headlines "Scientist discover people don't always wash their hands after going to the loo", or "Scientists confirm elephants are related to mammoths" would have elicited such high profile coverge!

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