Assignment2

ASSIGNMENT 2 cont.

Self study at S - star

i.e. Comparative Genomics

Page 3

What to compare? 3. Paralogues and Orthologues
•	Paralogous families
•	DNA – sequence differences between orthologous
•	Protein – sequence differences between orthologous
•	In J99, 337 genes are members of 113 paralogous families.
•	DNA – sequence differences between orthologous are mainly found in the third position of coding triplets.
-      8 genes with > 98 % nucleotide identity.
-      310 proteins with > 98 % amino acid identity.
What to compare? 4. Genomic Organization and Gene Order
-	Duplication
-	Inversion and Translocation
-	Gene order: conservation of immediate neighbors
-	That is alignment…alignment
?	Three single – copy genes in 26695 have complete or partial duplications in J99. 
?	10 Regions of inversion and/ or translocation. 
?	Gene order: 
-       84.7 % of the genes in J99 have the same neighbor on each side in both 
         genomes.
-       13.5 % are flanked by strain – specific gene on one or both sides.
-       Only 1.8 % have a different neighbor on one side because of organizational 
         differences.

Part II: Detecting Protein Interaction
?	Lives of biological cells are controlled by interacting proteins in metabolic and signaling pathways.
?	Protein interactions are traditionally detected using experimental methods
        -       Biochemical: co – immunoprecipitation or crosslinking
        -       Molecular biology: two hybrid system or phage display
        -       Genetics: unlinked noncomplementing mutant detection
?	Computational method based on:
               -       Subunit interfaces in protein structure databases
               -       Gene order
               -       Phylogenetic profile
               -       Gene fusion
Predicting Protein Interaction Based on Gene Fusion
Definitions:
?	Gene fusion event:  certain protein families in a given species consist of fused domains that usually correspond to two or more single, full – length proteins in other species.
?	Interaction: here is defined as either direct physical interaction or an indirect functional association (e.g., involvement in the same biochemical pathway or similar gene regulation).
?	Assumption: If a composite protein is uniquely similar to two component proteins in other species, the component proteins are most likely to interact.