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Decoding the last wild horses

University of Copenhagen research team cracks the Przewalski horse genome

Galloping around the steppes of Mongolia, Przewalski horses are the last of the truly wild horses in the world. Aggressive, thick muscled, worshipped by the communities and even acting as protection for other animals against wolves – they represent the untamed ‘one that got away’ as far as partnering humans through history might go.

The Przewalski [pronounced ‘Shavalskee’, ed] is a horse is from Mongolia, and has never been tamed because of its aggressive nature. Mongol horses are in general best known for their role as the war steeds of Genghis Khan. But even he had to most likely give up on the specific breed which is the Przewalski.

By the 1960s, they became extinct in the wild but a successful captive breeding programme and reintroduction to their native Asian steppes has recovered the population. Associate Professor Ludovic Orlando’s team of ancient genome hunters based at the UCPH Centre for GeoGenetics have used cutting edge technology to study if the surviving horses were truly wild.

The fact that we can get this information from ancient material has its own ‘wow’ factor…

In fact, a few domesticated horses were used for breeding up the last remaining Przewalskis in captivity, leading to genetic contamination.

Tracks the health of genes over time

The years of captivity in Europe started in the early 1900s and coincided with two World Wars, severe stress levels for horses and uncertainty in fully tracking how they were bred. To compare and separate the gene mixing of the wild versus the domesticated horses, the team sequenced the genome of Przewalski’s horse specimens preserved in museum collections as well as their living relatives. They also sequenced the genomes of a variety of modern domesticates and a few ancient horses that lived well before horses were even domesticated.

This allowed them to understand the evolutionary history of horses, and comprehend the genetic consequences of domestication and captivity. They identified that genes linked to metabolism, behavior and reproduction showed important differences between Przewalskis and domesticates.

The horse’s genome. A graphical abstract of the research article (from Der Sarkissian et al, Current Biology 2015).

On the flip side, they could also find that both domestication and captivity entailed a genomic ‘cost’, leading to the accumulation of deleterious mutations within the genome, impairing gene functionality.

Genes are not just genes

Genomes never say much beyond the genetic foundations underlying the evolutionary origins of species. Our DNA has usually four alphabets – A,T,G,C. In particular C (for cytosine) is subject to several chemical modifications such as methylation, hydroxy methylation etc., each of which have a say in whether the underlying genetic sequence can be active.

And these signatures are progressively lost once the animal is dead. Now the Orlando group (among others) exploiting the features of DNA degradation post-mortem to trace back modifications on cytosine (C) in the ancient genome are able to say if they were methylated or not back in time when the animal was still alive – thus allowing us an educated guess about their gene activity.

Ludovic Orlando: “The study gives a precise, unbiased, feedback to conservation efforts.”

In particular, they trace a chemical process called ‘cytosine deamination’- where Cs that were once methylated would change to another alphabet called ‘T’. Dramatic deamination is avoided by other dominant parts of the live cell machinery that ‘repair’ such deaminated Cs. However, in the event of death, deamination increases strongly with no competing process to prevent it.

In a similar manner, the team has used another innovative method to map out sites where protein structures called nucleosomes would have once positioned themselves. Nucleosomes are scaffold structures around which our DNA is wrapped and compacted into an ultra small space. So, if a gene was to be active, it has to first free itself from these tight nucleosomes to start becoming active.

Technique used to conserve condors

The fact that we can get this information from ancient material has its own ‘wow’ factor.

But using all this information and gene mapping, we can speculate on the activity state of genes that have shown the greatest differentiation between wild and domesticated horses over time.

The study gives a precise, unbiased, feedback to conservation efforts, Dr Orlando says. We can go back and hone in on which individuals to breed in order to get back to the original genetic makeup of the Przewalski horses, not just relying on genetic sequence information.

Ludovic Orlando: “We can get reasonably accurate maps for up to 1, perhaps 2 million years, but then DNA is simply too fragmented to be exploitable”

Furthermore, he is happy to note, these approaches are being used in conservation breeding programs for other endangered species – such as the South American Condor – the bird with the greatest wingspan on earth. There are only a few hundred Condors left. However, he adds, precision genomics will mean little in conservation if the environmental factors around the animals are not favorable such as poaching, societal awareness, governmental will to conserve.

In the case of the Przewalski’s horse, the recovery from a few animals to over 2,000 horses roaming the steppes is a case of science and society working together.

Can we bring back the dinosaurs?

Michael Crichton’s film Jurassic Park featured some futuristic science. Using broken bits of ancient dinosaur DNA, they built dinosaurs by filling in blanks in the genetic sequence using related species such as reptiles and amphibians.

As early as last year, the first synthetic chromosome was manufactured in a lab. Now, if we can get the complete ancient genetic blueprints of a human that lived up to 700,000 years ago – which also happens to be the oldest genome ever sequenced (also from the UCPH Centre for GeoGenetics) – then what? So, I asked Dr. Orlando, why not bring back extinct species?

“When the 700,000 year old genome project was underway we could see the deleterious effects time has on specimens however naturally well preserved the fossils may be,” he says.

“Our guess would be that we can get reasonably accurate maps for up to 1, perhaps 2 million years, but then DNA is simply too fragmented to be exploitable! No dinosaurs will ever walk around in our time I am afraid!”

Link to the original research article here.

Links and more information in fact box upper right.

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