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Re: [Indo-Eurasia] The limitations of ancient DNA studies

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  • Steve Farmer
    Further on epigenetic (and specifically gene-environmental) effects that grossly limit our ability to reconstruct phenotype from genotype, which I touched on
    Message 1 of 2 , Oct 1, 2010
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      Further on epigenetic (and specifically gene-environmental) effects
      that grossly limit our ability to reconstruct phenotype from genotype,
      which I touched on in the post below from last night: This paper
      appeared in PLoS Genetics this morning:

      http://tinyurl.com/26xjfg7 (open access)

      Gerke et al., "Gene–Environment Interactions at Nucleotide Resolution"

      You have to read between the lines to see the importance of this paper
      to ancient DNA studies, but its pessimistic consequences are strong
      ones. A brief snippet, grabbed in a rush (and what isn't done in a
      rush these days?); you'll have to go to the paper itself for
      explanations of "sporulation efficiency" and "QTN effects", etc.:

      > Regardless of the approach taken in the future, our results clearly
      > show that the genetic architecture of sporulation efficiency is
      > environment-dependent. QTN effects cannot be understood without
      > taking into account contextual factors such as the environment's
      > influence on cell physiology. We expect that quantitative
      > biochemical measurements will be required to illuminate what is
      > happening inside the cell and bridge the missing link between
      > genotype and phenotype.

      Unfortunately, in dealing with ancient DNA, we can't know what is
      "happening in the cell." The implication, though not drawn out
      in this paper:

      Old style ancient DNA studies are of far less utility in reconstructing the past than anyone guessed a few years ago.

      Rushed -
      Steve

      On Sep 30, 2010, at 9:17 PM, Steve Farmer wrote:

      > Dear List,
      >
      > A few years ago a lot of press was given to the supposed revolution
      > that was coming in studies of ancient DNA. It was well-known at the
      > time to specialists in the field -- as I pointed out in a number of
      > posts at the time -- that DNA begins to break down immediately
      > after death, often along mutational hot spots, making much of the
      > data collected by sequencing recovered ancient DNA suspect. But the
      > skepticism about the reliability of sequencing techniques often
      > buried deep in technical papers rarely were mentioned in the popular
      > scientific press, which preferred to talk about the (quite
      > ludicrous) possibility of reconstructing Neandertals or mammoths, etc.
      >
      > Claims have been made in the last few years that new sequencing
      > techniques might help us get around contamination and decomposition
      > problems. But now those hopes are beginning to break down.
      > Ironically the new skepticism comes from studies from the Max Planck
      > Institute for Evolutionary Anthropology, which (in the well-known
      > work of Paabo's group) has been the source of much of the creative
      > work in the field and much as well of the popular hype.
      >
      > Richard Meadow, of the Peabody Museum at Harvard, today passed a
      > summary from biotechniques.com of the following important paper,
      > which suggests that the field may have already reached its
      > theoretical limits in reconstruction:
      >
      > Heyn, P., U. Stenzel, A.W. Briggs, M. Kircher, M. Hofreiter, and M.
      > Meyer. 2010. Road blocks on paleogenomes—polymerase extension
      > profiling reveals the frequency of blocking lesions in ancient DNA.
      > Nucleic Acids Research. 38: e161.
      >
      > Here's the summary, which is suggestively titled "Ancient DNA
      > reaches a dead end?"
      >
      > http://tinyurl.com/3y5243f
      >
      > Here is a link to the original paper (open access):
      >
      > http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938203/
      >
      > The paper concludes:
      >
      >> it seems that ancient DNA research will soon reach a hard limit at
      >> which no major unexplored potentials remain for the recovery of
      >> additional sequences. Thus, despite huge recent advances in ancient
      >> DNA techniques, there is little hope for ever expanding ancient DNA
      >> research to fossils that are much older than the ones currently
      >> accessible to genetic analysis.
      >
      > What is most frustrating is that the limits in useful temporal
      > reconstructions as I understand it even under the best circumstances
      > are suggested to be well under ca. 50K years BP, which means that
      > future ancient DNA studies will not be of any use in studying the
      > emergence of anatomically modern man, which may go back to ca. 200K
      > BP.
      >
      > The prospects for future advances in ancient DNA studies get even
      > worse when we factor in not just ancient DNA studies but the
      > epigenetic
      > processes (involving, e.g., methylation of DNA) needed to understand
      > how ancient DNA was expressed in ancient organisms, including early
      > man.
      >
      > Epigenetics is the hottest study currently in the
      > genetic field, but if you search for papers in PubMed (the National
      > Library of Medicine) data base, you won't find even ONE abstract yet
      > that links the term "epigenetics" with "ancient DNA." It is almost
      > as if the field were ignoring the problem entirely.
      >
      > I've only seen one major reference so far to issues that the
      > epigenetic revolution poses for ancient DNA studies, in this paper
      > from the same Max Planck group, published in December 2009:
      >
      > http://nar.oxfordjournals.org/content/38/6/e87
      >
      > The paper seems outwardly optimistic, but as the new paper by Hyne et
      > al. suggests, even ignoring epigenetic issues involving genetic
      > expression the limits in our reconstructive knowledge of ancient DNA
      > may have already been reached.
      >
      > It will be interesting to see if this new paper gets any press at
      > all. I rather doubt it.
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