Talk:CH391L/S13/Ancestral Sequence Reconstruction

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  • Gabriel Wu 16:59, 18 February 2013 (EST): How does Pauling's proposal for ancestral gene construction relate to the actual discovery of DNA structure?
    • Benjamin Gilman 13:21, 21 February 2013 (EST): The Pauling and Zuckerkandl paper came out when the only protein sequence information we had came from limited peptide sequencing methods like Edman degradation (N-terminal sequencing). You might add something about the shift to using DNA or RNA sequences to infer protein sequence once techniques like Maxam-Gilbert and Sanger sequencing showed up in the '70s.
    • Jeffrey E. Barrick 21:26, 24 February 2013 (EST):The idea, if not the algorithms, were probably fairly close to what goes on today.
  • Kevin Baldridge 17:00, 18 February 2013 (EST):How do the methods here compare with those used for phylogenetic placement based on ribosomal RNA sequences?
    • Jeffrey E. Barrick 21:26, 24 February 2013 (EST):Pretty much the same in theory.
    • Aurko Dasgupta 00:36, 25 February 2013 (EST): The techniques used to estimate the ancestral sequences are essentially the same. However, most protein sequences are nowhere near as conserved as ribosomal sequences.

Ancestral Organism Resurrection?

  • Gabriel Wu 17:06, 18 February 2013 (EST): What's the oldest intact DNA? What's the oldest speciesn being sequenced today?
  • Catherine I. Mortensen 15:05, 21 February 2013 (EST):Has anyone heard of H. Salinarum?
    • Benjamin Gilman 16:47, 21 February 2013 (EST): I know there's some debate about it, but it's possible that at least one sample of an ancient H. Salinarum ancestor is >100 million years old. A lot of people were skeptical because the genome didn't seem that different from those of current halophilic archaea, but at least some regions didn't match anything we know of now. I wonder if it's reasonable to assume that once they're adapted to high salt, halophiles might evolve more slowly because they face less competition.
    • Thomas Wall 21:47, 21 February 2013 (EST): This wiki entry is a good start if you are interested on the subjects
    • Thomas Wall 21:52, 21 February 2013 (EST): Here they found the half life of DNA in fossil samples, 521 years,
  • Gabriel Wu 17:08, 18 February 2013 (EST): Separate topic on sequencing wooly mammoths and neanderthals?
    • Jeffrey E. Barrick 18:30, 20 February 2013 (EST):We could call that topic Ancestral organism resurrection. It could also talk about synthesizing the 1918 Spanish flu. Here's a review that might help with that topic.
    • Thomas Wall 21:57, 21 February 2013 (EST): I always thought the coolest and somewhat plausible project for an animal was the Tasmanian Tiger (Thylacine), A museum was attempting to do it in Australia. That project was closed down but many more seemed to have sprung up. A recent paper about such things from a UT proff

Caveats and Limitations

  • Kevin Baldridge 17:10, 18 February 2013 (EST):On the topic of general to specific evolution, is there any consideration for hypermodified amino acids? Maybe the ancient proteins had post-translational modifications in the proteins that adjusted the specificity, but we don't know about it from the genetic sequence for the protein.
    • Aurko Dasgupta 23:16, 23 February 2013 (EST): I have yet to find any specifics on how post-translational modification could affect final protein specificity. That said, I think it's an extremely pertinent point, and will keep looking for something that answers this.
  • Siddharth Das 19:24, 19 February 2012(EST): With even the most powerful statistics tools and rigorous mathematics, how useful is this technology in terms of evolutionary studies, since it seems the genes themselves are inaccurate representations (varying mutation rate for the past million year, etc)? Furthermore, is it safe to assume that the genetic code was as conserved as it is today? There are exceptions even now; for example, in the fungus Candida, CUG codes for serine instead of leucine. On a different note, the wiki is very well organized.
  • Jeffrey E. Barrick 21:28, 24 February 2013 (EST): There's a nice study where they show that the methods used to reconstruct the ancestral sequences (whether parsimony or maximum likelihood) tend to overestimate the thermal stability of the reconstructed proteins because they favor "consensus" proteins. Link
  • Alvaro E. Rodriguez M. 21:39, 21 February 2013 (EST): One thing that seems to be missing in most topics currently is technical limitation to approaches like this. i.e. Do you need 2 sequences of a gene/protein or 10 to make it work.

Content and Formatting

  • Gabriel Wu 17:06, 18 February 2013 (EST): Can you include a little more detail in your figures? At least give some detail about the methods used to determine time and explain the acronyms (e.g. PNCA, GNCA, etc).
    • Alvaro E. Rodriguez M. 21:36, 21 February 2013 (EST): Adding to Gabriel's comment I already did some editing, but it would be better if you either define the acronyms and then use them or keep using the corresponding terminology.
  • Gabriel Wu 16:59, 18 February 2013 (EST): Remove the cost and methods of gene synthesis (or just reference the dna assembly section we've already gone over). Expand the codon optimization section (unless this fits better in somewhere else).
  • Jeffrey E. Barrick 17:16, 18 February 2013 (EST):Add a picture of the fluorescent proteins (take one from Matz Lab website?
    • Alvaro E. Rodriguez M. 21:36, 21 February 2013 (EST):Expanding on this, a visual on how the process is carried (a pipeline image) would be more useful for the reader.
  • Jeffrey E. Barrick 18:37, 20 February 2013 (EST):Please add the titles of papers in the bibliography on your own as is done in other topics. You might also send feedback to OWW to tell them the bibio extension is broken to see if someday they will fix it.

Reconstruction of co-evolution

  • Gabriel Wu 17:20, 18 February 2013 (EST): From Andre: Discussion of Red Queen hypothesis and how ancestral gene reconstruction can show us evolution of interactions between host and virus proteins.
    • Jeffrey E. Barrick 18:30, 20 February 2013 (EST):If it's specific proteins I'd put it in this topic. If it's whole viruses, I'd kick to it a whole-organism topic.

iGEM team connection

  • Neil R Gottel 16:31, 21 February 2013 (EST):This seems to be a tricky topic to find a link to iGEM, since I'm not finding any teams who have incorporated this into their projects. Therefore, we should do it. It also has an obvious tie-in to BEACON (evolution of proteins!), so that makes it doubly worth pursuing. Since these analyses tend to give higher-temp versions of proteins, we could potentially use this as a starting point for making heat-stable versions of various biotech/industrial enzymes, then tweaking/evolving to increase efficiency. The actual goal is to make some sort of new protocol that others can follow, and therefore cite when we publish in Nature. Or Science, I'm not picky.
    • Thomas Wall 23:02, 21 February 201 3 (EST): I think this might be a good idea, generate some buzz
    • Aurko Dasgupta 23:02, 23 February 2013 (EST): This is definitely something I'd support. The only thing is that we don't seem to have anyone with any background in sequence recontruction type stuff do we? If some grad student on campus works with this kind of thing, we should try to see if they'd be interested in advising anything done on a project involving the development of a functional reconstructed protein.
    • Jeffrey E. Barrick 20:59, 24 February 2013 (EST):What would be an interesting protein family tree to reconstruct? I feel like one would want to explore more than thermostability (esp. since there are some caveats to the reconstruction procedure where it may be making more consensus proteins than ancestral proteins).
  • Benjamin Gilman 16:51, 21 February 2013 (EST): Is "RetroBioBricks" too hard to say?
  • Kevin Baldridge 15:18, 25 February 2013 (EST):There were ideas thrown about for using reconstruction of more thermostable antibiotic resistance genes as a tool in synthetic biology?
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