CPHx: Morten Rasmussen, National High-Throughput Sequencing Centre, sponsored by Illumina – Exploring ancient human genomes

Exploring ancient human genomes
Morten Rasmussen, National High-Throughput Sequencing Centre, sponsored by Illumina


Why study ancient DNA?  By studying modern species, we can only add leaves to the end of the phylogenetic tree, but not to study the nodes, or extinct branches. [my interpretation.]

How do you get ancient DNA? Bones and Teeth, mainly.  Coprolites are now used as well, and soft tissue, if available.  Ice and sediments can also be used in some cases.

Characteristics: The colder and dryer the environment, the better quality of the DNA preservation.  Age is also a factor.  The older the DNA, the less likely it is to have survived.  More than 1 million years is the limit, if conditions were optimal.

Goldilocks principle.  There is a sensitivity limit – you need enough.  Some is too short – you need longer strands.  You also need to worry about modern DNA contamination – mostly microbial.  Thus, within those constraints, you need to work carefully.

Some advantages in next-gen seq tho – no need for internal primers, size constraints are ok, etc.

DNA barcodes are frequently used to look at biodiversity.  Align the sequences to look for conserved regions surrounding a variable region – allowing primers to be designed for either end of the variable region.  If sequences are identical, you can’t distinguish the origin of the DNA.  [obviously a different type of bar-coding than what we usually discuss in NGS.]

Ice core genetics.  Willerslev et al, Science (2007).  Interesting results found in the “silty” ice, which included DNA from warmer climate plants.

Late survival of mammoth and horse…  can use similar techniques as ice cores to soil cores.

Paleogenomics.  DNA is often highly fragmented and full of bacterial contamination.  A big part of this is finding the right sample.. Eg, look in greenland for good samples where the cold will have preserved samples well.  Hair sample found, which was eventually moved to denmark.

Big issue of contamination, however still has to be dealt with.  Fortunately, DNA is held inside the hair, so washing hair with bleach removes most surface contaminants without harming the DNA sample.  Gives good results – vastly better than bone results that can’t use that method.  (84% in this case is homo sapiens, versus 1% recovery for neanderthal bone.)

DNA damage:  Expected damage from ancient DNA as previously observed, but bioinformaticians did not see significant damage.  Turns out that Pfu was used in protocol in this round, and Pfu does not amplify Uracil.  This has the unexpected side effect of “removing” the damage.

Standard pipeline was used, mapping to hg18.  only 46% of reads mapped, because only uniquely mapped reads were used for the analysis.  Multi-mapped reads were discarded, and clonal reads were also “collapsed”.  Still, 2.4 billion basepairs covered, 79% of hg18, 20X depth.

Inference about phenotypic traits:

  • dark eyes
  • brown hair
  • dry earwax
  • tendancy to go bald

Of course, many of those could have been predicted anyhow, but nice to confirm.

Compared to other populations with SNP chip data.  Confirmed that the ancient greenland DNA places the sequenced individual near the chukchis and koryaks (Populations from northern siberia).  That’s good, because it also rules out contamination from the people who did the sequencing. (Europeans.)  Thus, this was probably from an earlier migration than the current greenlanders, consistent with known data about migrations to the region.

What does the future hold:

  • More ancient genomes
  • Targeted sequencing for larger samples.

Why targeted sequencing of ancient DNA?  If you capture the most important bits of DNA, you would generate more interesting data with less effort, giving the same results.


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