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Ancient DNA

Towards a million-year-old genome

Nature volume 499, pages 3435 (04 July 2013) | Download Citation

The sequencing of a complete horse genome from a bone dating to around 700,000 years ago sheds light on equine evolution and dramatically extends the known limit of DNA survival. See Letter p.74

The field of ancient DNA continues to break records. Ancient DNA and genomes provide a window on the recent evolutionary past and often reveal that history is more complex than we previously thought. Following on from the work of the evolutionary biologist Allan Wilson1 in the early 1980s, ancient DNA studies are now used to address three broad issues: the estimation of molecular rates of change using serially preserved samples; the testing of specific evolutionary hypotheses; and the estimation of changes in genetic diversity and population sizes through time. In this issue, Orlando et al.2 (page 74) address the latter two concepts in their report of the complete genome sequence of a horse that lived around 700,000 years ago. This genome is almost 10 times older than the previous record, which was for a Denisovan3, an archaic human dated at approximately 80,000 years before present*.

The Middle Pleistocene horse genome was obtained using a bone fragment recovered from Arctic permafrost at Thistle Creek, Canada. For comparison, Orlando and colleagues also sequenced the genome of a Late Pleistocene horse (from around 43,000 years before present) and a Przewalski's horse (Equus ferus przewalskii). The latter is considered the only remaining truly wild member of the Equus genus, and the new data show that it is the closest living relative of the domesticated horse. In addition, the authors sequenced the genomes of five domestic horse breeds (Equus ferus caballus) and a donkey (Equus asinus). They then used these data to estimate several evolutionary and population parameters of the horse, which has been a textbook example in evolutionary biology and palaeontology since early work4 in the 1950s. For example, they calculate the time to the most recent common ancestor of members of the Equus genus to be between 4.0 million and 4.5 million years ago (Fig. 1), approximately twice the previous estimate.

Figure 1: Horse origins.
Figure 1

Orlando and colleagues' phylogenetic reconstruction2 was based on the genomes of the present-day donkey, domestic horses and the Przewalski's horse, and those derived from horse bones dating to approximately 43,000 (Late Pleistocene) and 700,000 (Middle Pleistocene) years ago. This analysis allowed the authors to estimate the time to the most recent common ancestor of all members of the Equus genus to be between about 4.0 million and 4.5 million years ago.

Orlando et al. went on to show that the size of the horse population has fluctuated many times over the past 2 million years, particularly during periods of severe climatic change. Interestingly, they reveal that Przewalski's horse has retained substantial genetic diversity, a feature that could be significant for the species' future conservation. Furthermore, they identify genomic regions in domesticated horses that have been under positive selection; some of these might represent genetic signatures of domestication.

But the implications of this work go well beyond the evolution of horses, by also providing evidence for the limits of DNA survival. Until this study, many experts5,6 would have thought that it was impossible to recover a genome from a sample of this age because of the rapid degradation of DNA into ever shorter fragments that occurs following the death of an organism. The decay is driven initially by the body's own enzymes, and the actions of enzymes from microorganisms soon follow — death shuts down the normal defences that protect an organism against such fates. This process is, of course, affected by environmental conditions, including the presence of oxygen and water, the microorganisms present, pH and temperature. In general, the colder the environment, the slower the rate of DNA degradation (Fig. 2).

Figure 2: Survival of the coldest.
Figure 2

The rate of DNA decay varies with environmental conditions, as indicated by this plot of the estimated half-lives of 30- and 100-base-pair (bp) DNA fragments as a function of temperature7. The estimated ages and temperatures of material used to recover the genomes of a Neanderthal (N)10, a woolly mammoth (M)11 and the horse fossil discovered at Thistle Creek, Canada (H)2, are shown.

Orlando and colleagues' success is undoubtedly due to the extreme cold in which the bone resided and its resulting preservation, combined with advances in second-generation gene sequencing, including true single-molecule sequencing technology. Technical developments in DNA recovery and the construction of DNA-sequencing libraries also contributed to the authors' achievements. From this same sample, they were able to sequence 73 proteins, including some found in blood. This illustrates that other methods apart from DNA sequencing can now be applied, on a large scale, to studies of the deep past.

So just how long can animal DNA survive? Recent work has modelled the absolute limits of DNA survival, and suggested that DNA more than 1 million years old may be recoverable from very cold environments7. Interestingly, the age of the horse genome recovered by Orlando et al. falls comfortably within these predicted limits of DNA survival (Fig. 2), suggesting the tantalizing proposition that complete genomes several millions of years old may be recoverable, given the right environmental conditions. Indeed, Orlando and colleagues' study encourages us to wonder if it might be possible to recover DNA from a wide range of Middle Pleistocene samples. Of particular interest would be material from ancestral human species8 such as Homo heidelbergensis and Homo erectus9. Such genomic information, in combination with the Denisovan3 and Neanderthal10 genomes, would undoubtedly shed light on the evolution of humans and our hominin ancestors, in much the same way as Orlando and colleagues' study provides insight into the evolution of horses and the survival of DNA itself.

Notes

  1. 1.

    *This article and the paper under discussion2 were published online on 26 June 2013.

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  1. Craig D. Millar is in the Allan Wilson Centre for Molecular Ecology and Evolution, School of Biological Sciences, University of Auckland, Auckland 1010, New Zealand.

    • Craig D. Millar
  2. David M. Lambert is in the Environmental Futures Centre, Griffith University, Nathan 4111, Australia.

    • David M. Lambert

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Correspondence to Craig D. Millar or David M. Lambert.

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https://doi.org/10.1038/nature12263

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