References of "Rasmussen, Morten"
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See detailRecalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse.
Orlando, Ludovic; Ginolhac, Aurélien UL; Zhang, Guojie et al

in Nature (2013), 499(7456), 74-8

The rich fossil record of equids has made them a model for evolutionary processes. Here we present a 1.12-times coverage draft genome from a horse bone recovered from permafrost dated to approximately 560 ... [more ▼]

The rich fossil record of equids has made them a model for evolutionary processes. Here we present a 1.12-times coverage draft genome from a horse bone recovered from permafrost dated to approximately 560-780 thousand years before present (kyr BP). Our data represent the oldest full genome sequence determined so far by almost an order of magnitude. For comparison, we sequenced the genome of a Late Pleistocene horse (43 kyr BP), and modern genomes of five domestic horse breeds (Equus ferus caballus), a Przewalski's horse (E. f. przewalskii) and a donkey (E. asinus). Our analyses suggest that the Equus lineage giving rise to all contemporary horses, zebras and donkeys originated 4.0-4.5 million years before present (Myr BP), twice the conventionally accepted time to the most recent common ancestor of the genus Equus. We also find that horse population size fluctuated multiple times over the past 2 Myr, particularly during periods of severe climatic changes. We estimate that the Przewalski's and domestic horse populations diverged 38-72 kyr BP, and find no evidence of recent admixture between the domestic horse breeds and the Przewalski's horse investigated. This supports the contention that Przewalski's horses represent the last surviving wild horse population. We find similar levels of genetic variation among Przewalski's and domestic populations, indicating that the former are genetically viable and worthy of conservation efforts. We also find evidence for continuous selection on the immune system and olfaction throughout horse evolution. Finally, we identify 29 genomic regions among horse breeds that deviate from neutrality and show low levels of genetic variation compared to the Przewalski's horse. Such regions could correspond to loci selected early during domestication. [less ▲]

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See detailImproving the performance of true single molecule sequencing for ancient DNA.
Ginolhac, Aurélien UL; Vilstrup, Julia; Stenderup, Jesper et al

in BMC genomics (2012), 13

BACKGROUND: Second-generation sequencing technologies have revolutionized our ability to recover genetic information from the past, allowing the characterization of the first complete genomes from past ... [more ▼]

BACKGROUND: Second-generation sequencing technologies have revolutionized our ability to recover genetic information from the past, allowing the characterization of the first complete genomes from past individuals and extinct species. Recently, third generation Helicos sequencing platforms, which perform true Single-Molecule DNA Sequencing (tSMS), have shown great potential for sequencing DNA molecules from Pleistocene fossils. Here, we aim at improving even further the performance of tSMS for ancient DNA by testing two novel tSMS template preparation methods for Pleistocene bone fossils, namely oligonucleotide spiking and treatment with DNA phosphatase. RESULTS: We found that a significantly larger fraction of the horse genome could be covered following oligonucleotide spiking however not reproducibly and at the cost of extra post-sequencing filtering procedures and skewed %GC content. In contrast, we showed that treating ancient DNA extracts with DNA phosphatase improved the amount of endogenous sequence information recovered per sequencing channel by up to 3.3-fold, while still providing molecular signatures of endogenous ancient DNA damage, including cytosine deamination and fragmentation by depurination. Additionally, we confirmed the existence of molecular preservation niches in large bone crystals from which DNA could be preferentially extracted. CONCLUSIONS: We propose DNA phosphatase treatment as a mechanism to increase sequence coverage of ancient genomes when using Helicos tSMS as a sequencing platform. Together with mild denaturation temperatures that favor access to endogenous ancient templates over modern DNA contaminants, this simple preparation procedure can improve overall Helicos tSMS performance when damaged DNA templates are targeted. [less ▲]

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See detailTrue single-molecule DNA sequencing of a pleistocene horse bone.
Orlando, Ludovic; Ginolhac, Aurélien UL; Raghavan, Maanasa et al

in Genome research (2011), 21(10), 1705-19

Second-generation sequencing platforms have revolutionized the field of ancient DNA, opening access to complete genomes of past individuals and extinct species. However, these platforms are dependent on ... [more ▼]

Second-generation sequencing platforms have revolutionized the field of ancient DNA, opening access to complete genomes of past individuals and extinct species. However, these platforms are dependent on library construction and amplification steps that may result in sequences that do not reflect the original DNA template composition. This is particularly true for ancient DNA, where templates have undergone extensive damage post-mortem. Here, we report the results of the first "true single molecule sequencing" of ancient DNA. We generated 115.9 Mb and 76.9 Mb of DNA sequences from a permafrost-preserved Pleistocene horse bone using the Helicos HeliScope and Illumina GAIIx platforms, respectively. We find that the percentage of endogenous DNA sequences derived from the horse is higher among the Helicos data than Illumina data. This result indicates that the molecular biology tools used to generate sequencing libraries of ancient DNA molecules, as required for second-generation sequencing, introduce biases into the data that reduce the efficiency of the sequencing process and limit our ability to fully explore the molecular complexity of ancient DNA extracts. We demonstrate that simple modifications to the standard Helicos DNA template preparation protocol further increase the proportion of horse DNA for this sample by threefold. Comparison of Helicos-specific biases and sequence errors in modern DNA with those in ancient DNA also reveals extensive cytosine deamination damage at the 3' ends of ancient templates, indicating the presence of 3'-sequence overhangs. Our results suggest that paleogenomes could be sequenced in an unprecedented manner by combining current second- and third-generation sequencing approaches. [less ▲]

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See detailmapDamage: testing for damage patterns in ancient DNA sequences.
Ginolhac, Aurélien UL; Rasmussen, Morten; Gilbert, M. Thomas P. et al

in Bioinformatics (Oxford, England) (2011), 27(15), 2153-5

SUMMARY: Ancient DNA extracts consist of a mixture of contaminant DNA molecules, most often originating from environmental microbes, and endogenous fragments exhibiting substantial levels of DNA damage ... [more ▼]

SUMMARY: Ancient DNA extracts consist of a mixture of contaminant DNA molecules, most often originating from environmental microbes, and endogenous fragments exhibiting substantial levels of DNA damage. The latter introduce specific nucleotide misincorporations and DNA fragmentation signatures in sequencing reads that could be advantageously used to argue for sequence validity. mapDamage is a Perl script that computes nucleotide misincorporation and fragmentation patterns using next-generation sequencing reads mapped against a reference genome. The Perl script outputs are further automatically processed in embedded R script in order to detect typical patterns of genuine ancient DNA sequences. AVAILABILITY AND IMPLEMENTATION: The Perl script mapDamage is freely available with documentation and example files at http://geogenetics.ku.dk/all_literature/mapdamage/. The script requires prior installation of the SAMtools suite and R environment and has been validated on both GNU/Linux and MacOSX operating systems. [less ▲]

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