Archive for the ‘research’ Category

Summary: Metagenomics, fruit flies, and lessons learned

December 6, 2007

On November 8th, Nature published two cool articles about metagenomic studies of twelve Drosophila (“fruit flies”) species. In the the first paper (click here), The Drosophila 12 Genomes Consortium (D12GG) compared the complete genomic sequences of the twelve Drosophila species, which included the model organism species Drosophila Melanogaster. Although the twelve species are related, they exhibit a surprising amount genetic biodiversity. For example, the evolutionary distance between D. Grimshawi and D. Melanogaster is the same distance as between humans and lizards. As a side note, six months earlier (in May 2007), PLoS Genetics published a similar metagenomic comparison of Drosophila (click here for the paper). In the PLoS paper, Hahn et al. present the (somewhat obvious) conclusion: “the apparent stasis in total gene number among species has masked rapid turnover in individual gene gain and loss.”

On November 8, Nature also published this paper (click here), in which Stark et al. (including Hahn) used the data from D12GG’s research to demonstrate a truly novel insight about the connection between conserved metagenomic sequence motifs and functional elements. The result of this paper allows us to infer the presence of functional elements with a accuracy far surpassing previous methods. Specifically, Stark et al. show how to infer the following functional elements, based on a metagenomic sample:

  • Protein-coding regions: have highly constrained condon substitution regions, and indels have a bias for multiples of three.
  • RNA genes: tolerate substitutions that preserve base pairing.
  • miRNA: can be detected by looking for conserved palindromic stem sequences, which mutable loop sub-sequences between the two palindrome pieces.
  • Regulatory motifs: have high levels of genome-wide conservation.
  • Post-transcriptional motifs: are typically strand-based conservations.

“DNA in a tigh squeeze”

October 16, 2007

Today Rob Phillips (http://www.rpgroup.caltech.edu/) gave a talk titled, “DNA in a tight squeeze: the other life of a macromolecular assembly.”

Phillips et al. study the atomic-level physics of DNA.  Their recent work focuses on DNA loops which are formed when transcription factors bind to regulatory sites.  Specifically, they modified the lac operon such that they can insert sequences of arbitrary length and content between the Oid and O1 sites.   A surprising result is that DNA is happiest to make loops of 75.5 base pair lengths, whereas the persistence length for DNA is 115 base pairs.  I think this result has ramifications for our understanding of the fitness of regulatory regions. I would like to see an experiment which explores evolutionary fitness with regard to loop length between cis-regulatory sites.

Phillips also showed results from his study correlating the osmotic pressure inside a viral capsid to the speed of genetic ejection.  His results show that viruses eject genetic material (into their host cell) very quickly at first.  However, as the inter-viral osmotic pressure declines, the rate of ejection also drops.  Eventually, the pressure reaches a point where no genetic material is ejected at all.  I have several questions about the content of the genetic material which may or may not be ejected.  Does it transcribe into a functional protein?  Or, does this “tail” material contain garbage which can safely be left inside the virus?

I find this research exciting because it intersects physics, chemistry, biology, statistics, and computer science.

(Finally: check-out the VIPER project for atomic-level exploration of viral structures) 

Introduction to Computational Proteomics, latest issue of PLoS

August 1, 2007

Here is a TERRIFIC article in the recent issue of PLoS:

“Introduction to Computational Proteomics” by Jacques Colinge and Keiryn L. Bennett.

I like this article because it summarizes a large body of research, and it’s written for a non-CompBio audience. Introductory articles in CompBio are rare. Well-written introductory articles are even rarer. Enjoy.


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