User:J. C. Martinez-Garcia/Notebook/HMS Activities/2008/10/15

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The Pilpel papers

  1. R. Kafri, O. Dahan, J. Levy, Y. Pilpel (2008): Preferential protection of protein interaction network hubs in yeast: Evolved functionality of genetic redundancy. PNAS January 29, 2008, Vol. 105, pp. 1243-1248.
    • Main results: Compensated duplicates are not randomly distributed within the protein intercation network but are there strategically allocated to the most highly connected proteins.
    • Suggestions:
      1. Vulnerable nodes are often protected by redundancy.
      2. The association between redundancy and protein connectivity becomes even more significant among the ancient duplicates, so these functional overlaps have undergone purifying selection.
      3. Redundancy tends to be preserved among some of the central proteins in the cellular interaction network.
    • Questions:
      1. Why redundancy is typically transient on evolutionary time? Compensation against a mutation allows adaptability but since the mutation have no effect in the phenotype, it would be not selected, and will be gradually lost (short term adaptability).
      2. Since duplicate genes evolve more slowly than singletons, some essential functions are more likely endowed with redundancies. How these functional overlaps have been fixated in the population after the duplication event? How the system has evolved to use these functional overlaps? The first question has been answered, but the second one no.
      3. Redundancy protect essential nodes? It seems yes.
      4. Are some modules in the network of interaction more robust than others? The oldest ones?
      5. Are protein protected by redundant-based systems distributed in the same way in the families of proteins? (regulatory proteins more protected than the other ones, it seems that both post-transcriptional regulators are metabolic regulators are more present).