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When comparing the number of links (=degree), young and old superfamilies make
Revision as of 07:25, 29 September 2006
Linking evolution of protein structures through fragments
Here we use a strucutural fragment library to investigate evolutionary links between protein folds. We show that 'older' folds have relatively more such links than 'younger' folds.
At present there is no universal understanding how proteins can change topology during evolution, and how such pathways can be determined in a systematic way. The ability to create links between fold topologies would have important consequences for structural classification, structure prediction and homology modelling. It has been proven difficult however to show the evolutionary relevance of such links between topologies based on geometrical measures. Here we use our a previously determined age measure for protein folds or superfamilies  to investigate the effect of structural fragments on protein structure evolution .
When comparing the number of links (=degree), young and old superfamilies make with other superfamilies, it becomes clear that younger folds have relatively fewer linke than older folds(Figure 1). This results is significant, with the wilcoxon unpaired test assigning an p-value of 1.2e-09.
Similarly we can compare the number of link each fold has with young and old folds respectively. Again we see that fold share significantly fewer links with the goup of young folds (Figure 2).
- Figure 2 shows that the difference in links becomes stronger when we consider larger fragment lengths.
- show figure with links between set of old folds and new folds
- need brief discussion of evolutionary model
The fragment library generated for this study, contains fragment-pairs of length 10,15,20 and 30, with a maximum allowed gaplength of 2,3,4,6 respectively. All fragments are based on pairwise comparisons between structural domain as defined by SCOP. The pairs are scored for similarity purely on structural grounds, using the coordinates of the c-alpha atoms. This is in order to avoid dependencies between fragments and age estimates, which are generated through fold recognition techniques using on sequence similarity.
All possible pairwise fragments between two domains of the given lengths are first screened and aligned using a method similar to the prefilter used by MAMMOTH . Each fragment pair with an alignment score above a threshold is then superimposed to create an RMSD score for the fragment pair.
Age estimates for protein folds or superfamilies are generated using fold recongnition of structural domains on a set of completed genomes. The occurrence patterns of such predictions, are analysed with a parsimony algorithm to estimate an age for a superfamily or fold, for more details see .
The age of a fold or superfamily is based on a score between [0.0,1.0] with 0.0 indicating a last common recent ancestor at the leafs (youngest), and 1.0 indicating present at the root of the species tree (oldest). Here an 'old' fold is defined as a fold with an age of 1.0, and a 'young' fold with an age < 0.5
Since no consideration of secondary structure is taken into account, the amount of shared fragments needs to be normalised for the amount a fragment occurs in general. Friedberg and Godzik (2005) used a used a superfamily based normalisation to overcome this problem . We use a similar approach, although the fragment-pairs in this study are based on structural similarity only, whereas riedberg and Godzik (2005) used a combination of sequence and structural similarity.
A link between two superfamilies (I and J) is established when f(I,J) > 0.1, which is calculated as:
Here Sim(A,B) is the number of shared fragments between two set of domains (e.g. superfamilies), and A is the set of all domains. In this studies we do not consider self-similarity of superfamilies.
We show that younger folds have relatiely fewer shared fragments with other fold, than old protein fold. This might indicate that evolutionary links above superfamily or fold level could be established, through such shared fragments.