Julius B. Lucks/Meetings and Notes/20070523

Protein Evolutionary Rates

• dS = # synonymous changes per site
• dN = # non-synonymous changes per site
• calculate these quantities by comparing coding sequences of similar organisms that have diverged (S. ceriviciae and S. bayanus diverged 20 million years ago)
• Drummond, PNAS, 2005 [1]
  • dN has a range of several orders of magnitude
  • what is known is that highly expressed proteins evolve slowly (small dN)
  • expression level, CAI, abundance, # interactions, length, network centrality, fitness of knockout - all correlate with dN
• Drummond, MBE, 2006 [2]
  • principal axis when do Principle Component Regression is: expression level, CAI, abundance - no other relevant axis
    • Principle Component Regression - take axes that find with Principle Component Analysis (PCA), and regress these with an outcome variable (here dN)
  • the problem is protein interaction data is very unreliable [3]
• Plotkin and Fraser, MBE, 2007, [4]
  • make all variables on equal footing by adding noise to them to equal the noise in the protein interaction data
    • find that the principle component found above drastically reduced
  • hidden variable analysis to see if can extract anything from the noisy data
  • contentious because protein interaction data is biased towards picking up interactions between highly abundant proteins, and thus slowly evolving proteins - conflation

Side Note

• how does PCA deal with variables that have different scales?
  • 2 options
    • normalize all variables to have an internal variance of 1 (and 0-mean)
    • do PCA on the rank of the variables (non-parametric)

Bibliography

Error fetching PMID 1763012
Error fetching PMID 11607249
Error fetching PMID 16505372
Error fetching PMID 16164990
Error fetching PMID 3005124
Error fetching PMID 6221115
Error fetching PMID 17460793
Error fetching PMID 17222055
Error fetching PMID 16176987
Error fetching PMID 16237209
Error fetching PMID 17347158
Error fetching PMID 12000970
Error fetching PMID 13498456
Error fetching PMID 11028996
Error fetching PMID 15159530
Error fetching PMID 11451474
Error fetching PMID 15590784