Archive April 2010

Cloning extinct species #1: A how-to guide Hilary Miller Apr 30

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 Fancy seeing herds of mammoths running across the tundra, moa crashing through the undergrowth, or perhaps a tasmanian tiger lurking in the Aussie bush? Well in the near future these images might not just be the stuff of far-fetched Hollywood movie plots.  Advances in molecular biology and genomics mean that the ability to clone extinct species is getting closer. In theory, at least.  In this post I’m going to look at how one would go about bringing back to life their favourite extinct species, and in a later post I’ll discuss whether we should bother.

The technology required to clone extinct species is largely already here.  In fact, in November 2008 Japanese researchers reported cloning mice that had been frozen 16 years, and last year researchers in Spain reported cloning the bucardo (Pyrenean ibex), a subspecies of the Spanish ibex which went extinct in 2000, from a piece of frozen skin (although the animal died soon after birth).  Whole genome sequencing for extinct species is also becoming a reality – a partial genome sequence for the mammoth was published in Nature in 2008.   

The Woolly Mammoth may have had its genome sequenced, but cloning is still a long way off

While a genome sequence is a good start for resurrecting an extinct species, that alone is not enough.  In order to turn the DNA sequence of the genome into a living organism, the DNA has to be packaged into chromosomes and the information in the DNA expressed in living cells.  Conventional reproductive cloning (like that used to create Dolly the sheep) is performed using Somatic Cell Nuclear Transfer (SCNT), where the genetic material (ie the nucleus of a cell) from one organism is transferred into an egg from which the nucleus has been removed.  Because the nucleus that is transferred comes from a somatic cell, it already has a full diploid genome (ie 2 copies of each chromosome), and with a bit of kick-starting behaves like a freshly fertilized egg, developing into an organism identical to the one from which the nucleus came from.   

So to clone an extinct species using this method, you would need a closely related living species to provide an egg, and an intact nucleus containing a full set of chromosomes in good condition.  This is where things get tricky, as the DNA extracted from remains of extinct organisms is normally extremely degraded.  Even obtaining genome sequences from this material is only possible due to the advent of high throughput “next generation” sequencers, which can sequence billions of short fragments of DNA.  Heavy duty computer power is then required to stitch those sequences back together to decipher the genome sequence – a bit like a giant jigsaw puzzle.  Having a genome sequence for a closely related species for comparison helps enormously with this assembly, as it can be used as a sort of template on which to assemble the genome of the extinct species.   

Once you have the genome there are two ways in which (theoretically) you could rebuild the chromosomes of the extinct organism. Firstly, you could modify the DNA of a closely related species at each base that it differs from the extinct species.  For instance in the case of mammoths you could use African elephant DNA, which differs at about 400,000 sites.  Or alternatively, you could synthesize the whole genome from scratch.   However, so far only small bacterial genomes have been successfully synthesized, and then there is the problem of how to package the synthesized DNA into chromosomes and enclose the whole lot in a nuclear membrane.  These are not a trivial problems, as for many extinct species we don’t even know how many chromosomes there were, let alone which bits of DNA go where*.    

Of course these problems of rebuilding a genome can be circumvented if well-preserved tissue from the organism is available. If this is the case, an intact nucleus could be transferred directly a la Dolly the sheep.  This was the method used to clone the bucardo.  In 1999, researchers in Spain had the foresight to take skin samples from the last living bucardo, and froze them in liquid nitrogen.  The bucardo genetic material was then transferred into the eggs of a domestic goat, and the resulting embryo implanted into other species of spanish ibex or goat-ibex hybrids.  Researchers at the Audubon Centre for Research of Endangered Species (part of Audubon Nature Institute) are also using this method to clone critically endangered species such as the african wildcat.    

Using an intact nucleus from frozen tissue is obviously a much easier approach than rebuilding a whole genome from scratch, but for the majority of extinct species we don’t have a good enough tissue source.  Even exceptionally well preserved remains, such as those frozen in permafrost, show significant amounts of degradation, and the chances of finding an intact nucleus with undegraded DNA in a specimen that is several thousand years old are virtually nil.  Organisations around the world are now beginning to realise the importance of frozen tissue resources, and are creating frozen zoos, where archives of tissue from endangered species are cryopreserved for future use.  These resources won’t help resurrect the mammoth, but might facilitate future cloning endeavours on critically endangered species.  

Its also unlikely we’ll be seeing cloned moa, huia or giant eagles any time soon, as somatic cell nuclear transfer currently only works in mammals.  No one has yet successfully cloned a bird, reptile, amphibian or fish using these methods, because differences in the structure of the eggs in these species provide added complications.  Oh and you can forget about cloning dinosaurs too.  Although researchers at North Carolina State University have claimed to have extracted protein from dinosaur bones, no DNA has been found and it seems extremely unlikely that DNA could survive intact for more than a few hundred thousand years.  Virtually all reports of DNA extracted from samples that are many millions of years old have failed closer inspection, so it seems that the idea of extracting DNA from dinosaur blood found in mosquitos fossilized in amber belongs firmly in the realm of fantasy.  

* This news feature in Nature provides more detail and a really nice explanation of the methodological difficulties that have yet to be overcome with this type of cloning

Rare giant gecko turns up (dead) in mainland sanctuary Hilary Miller Apr 22


Here’s one from the good news but bad news file:  The good news is that a Duvaucel’s gecko (Hoplodactylus duvaucelii) has been found on the New Zealand mainland for the first time in nearly 100 years.  The bad news is that it was found dead in a mouse trap.

Duvaucels geckos are the largest of our native geckos, and one of the biggest geckos in the world, growing to up to 30cm in total length.  They are found on a number of offshore islands off the north-east of the North Island and in Cook Strait, and were thought to be extinct on mainland New Zealand.  The last recorded sighting of this species on the mainland was near Thames in the 1920s, but subfossil remains have been found on both the North and South Islands, suggesting it was once widespread across the country. 

The dead gecko was found at Maungatautari, in the Waikato.  Maungatautari is a 3400 ha nature reserve ringed with a predator-proof fence, making it the largest pest-free area on the mainland.  Many rare species have been released into the sanctuary, including kiwi, kaka, takahe and hihi, and reintroductions of many more species are planned.  The Duvaucel’s gecko find suggests that there is a remnant nautral population of the species in the sanctuary, which somehow survived the years when the area was overrun with introduced predators. The hunt is now underway for more of the geckos (which will hopefully be found alive).

This discovery shows that you never know what you might find when you protect an area instead of mining it.

More on the discovery on Stuff.

Freaky bioluminescent creatures from the deep on Hilary Miller Apr 20

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A great new video out on today has Edith Widder describing some clever applications of bioluminescence in deep sea organisms.

Some 80 to 90 percent of undersea creatures make light — and we know very little about how or why. Bioluminescence expert Edith Widder explores this glowing, sparkling, luminous world, sharing glorious images and insight into the unseen depths (and brights) of the ocean.

Play your genes Hilary Miller Apr 14

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Ever wondered what your favourite gene would sound like if it was a melody? Well here’s a website where you can find out. 

Basically what it does is take the DNA sequence, convert it to amino acids, and assign each amino acid to a musical note (with some modifications to make it more musical, described here).  There is also a complicated way of assigning rhythm. 

Gene2music is the brainchild of Rie Takahashi, Jeffrey Miller, and Frank Pettit at UCLA.

Tasmanian devil facial tumour disease: too good a match for the immune system Hilary Miller Apr 13

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A central premise in conservation genetics is that high genetic diversity is good for a species’ continued survival, and low genetic diversity is bad. This seems intuitively obvious (after all, we all know that you shouldn’t marry your cousin) but actually finding examples in nature where we can say for sure that low genetic diversity has contributed to a population’s demise is difficult.   

However, the recent decline of tasmanian devil populations due to disease provides an excellent example of the perils of low genetic diversity.  Wild devil populations in eastern Tasmania have been decimated in recent years by devil facial tumour disease (DFTD).  This nasty disease is a transmissible cancer spread by biting, and causes large tumours to form around the mouth, interferring with feeding and eventually causing death.  Kathy Belov’s group at the University of Sydney has been studying the genetic basis of DFTD susceptibility in devils and has found that a lack of variation in immune system genes is responsible for the spread of the cancer in some populations.    

Tasmanian devil with facial tumour disease (photo: Menna Jones)

Belov’s group has been studying the genes of the Major Histocompatibility Complex, or MHC.  MHC molecules are a crucial part of the immune system in vertebrates, as they are responsible for recognising foreign invaders and mounting an immune response.  MHC molecules are also an important part of the process of self/non-self recognition that prevents the immune system attacking the body’s own cells.  MHC genes are normally highly variable in populations, with a large number of different alleles (or variants) for each gene.  This variability allows for a wide array of foreign pathogens to be resisted and accounts for differences in disease resistance among individuals.  Thus, populations with low or no variation at MHC genes are potentially susceptible to disease epidemics, as all individuals in the population will be equally susceptible to novel diseases.   

Devil populations in eastern Tasmania have low levels of genetic diversity due to reductions in population size over the last 150 years.  DFTD is so virulent in these populations because the tumours have the same MHC type as healthy devil cells.  Being an infectious cancer, transmission of DFTD between individuals is a bit like a skin graft or organ transplant. If the tissue’s MHC type matches, the transplant is accepted, if not it is rejected.  Because the MHC types of the tumour and the devil match, DFTD cells are not recognised as foreign so no immune response is mounted.  And because of the low genetic diversity, all devils in the population have similar MHC types meaning the disease can easily spread from one individual to another. 

DFTD has spread rapidly throughout eastern Tasmanian populations, causing a 90% decline in total devil numbers.  However, a population at West Pencil Pine in northwestern Tasmania has much lower prevalence of DFTD, suggesting this population harbours animals that are resistant to the disease.  New research by Belov’s lab published in Proceedings of the Royal Society of London last month shows that these populations have differences in their MHC makeup that appear to allow them to resist the disease. 

Here the story gets a little (more) complicated: Tasmanian devils have multiple MHC genes (up to 7 genes each), which fall into two groups on the basis of their DNA sequence.  The tumour cells have both group 1 and group 2 variants, as do the individuals from the susceptible eastern populations.  However the northwestern populations harbour a greater diversity of MHC types, and many individuals from these populations have MHC types which have only either group 1 or group 2 sequences.  None of these individuals have succumbed to DFTD, suggesting they are resistant to the disease.  Belov’s group proposes that in individuals with only group 1 sequences, the immune system will recognise the group 2 sequences on the tumour as foreign and resist it (and vice versa for individuals with only group 2 sequences).   This has yet to be tested in practice, as it is obviously difficult to get permission to infect an endangered species with a deadly disease.  However, these findings are promising for the continued survival of the species and may have a significant impact on their conservation management.

Siddle HV, Kreiss A, Eldridge MD, Noonan E, Clarke CJ, Pyecroft S, Woods GM, & Belov K (2007). Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial. Proceedings of the National Academy of Sciences of the United States of America, 104 (41), 16221-6 PMID: 17911263

Siddle, H., Marzec, J., Cheng, Y., Jones, M., & Belov, K. (2010). MHC gene copy number variation in Tasmanian devils: implications for the spread of a contagious cancer Proceedings of the Royal Society B: Biological Sciences DOI: 10.1098/rspb.2009.2362

New species of giant lizard ’discovered’ in the Phillipines Hilary Miller Apr 08


In Biology Letters this week is the report of a new giant monitor lizard discovered in the Phillipines.  Varanus bitatawa is 2m long, brightly coloured and has a double penis, and lives high up in the trees on the island of Luzon. 

It always amazes me when new species of large vertebrates are discovered in this day and age, when you would think that the majority of the world has been given a thorough going-over, and that 2m long lizards would have been noticed.  Actual new discoveries – as in “thats the first time we’ve seen THAT animal”, as opposed to an organism thats been known about for years but only been named as a separate species on the basis of DNA analysis – are pretty rare these days.  So I was slightly disappointed to find out that Varanus bitatawa is only a new discovery from a western scientific perspective - Filipino tribal hunters have of course known about it for years. 

National geographic has more on the discovery here.

Varabus bitatawa (photo by Joseph Brown)

Songbird genome published Hilary Miller Apr 01

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The genome of the zebra finch was published in Nature today and is free to access here. This is the second bird species to have its genome published – the other one being the chicken.  The zebra finch is a member of the Order Passeriformes (the songbirds) and is something of a model organism in neurophysiology.  Not surprisingly its genome has a number of interesting features associated with song and vocal communication.  I hope to have some time to write more about the songbird genome later but in the meantime here’s a summary from Nature:

The genome of the zebra finch – a songbird and a model for the study of vertebrate brain, behaviour and evolution – has been sequenced. Its comparison with the chicken genome, the only other bird genome available, shows that genes with neural function and implicated in cognitive processing of song have been rapidly evolving in the finch lineage. The study also shows that vocal communication engages much of the zebra finch brain transcriptome and identifies a potential integrator of microRNA signals linked to vocal communication.

Male zebra finch (photo from Wikimedia Commons)

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