Comparative Approach
• Uses multiple evolutionarily related RNA sequences – to obtain structure
• Homologous RNA sequences - same secondary structure
• Predicting secondary structures for each individual sequence - produces errors
• Group of aligned RNA sequences --> comparing all predicted structures --> draw a
consensus
• Commonly adopted structure selected
• Other possible structures can be eliminated in the process
COVARIATION
RNA functional motifs - structurally conserved
Homologous
sequences evolve
Mutation occurring in
Maintain base pairing
one position
and the stability (of
secondary structure)
Mutation in the
corresponding basepairing position
Comparative Based Algorithms
Use
pre-alignment
Do not use
pre-alignment
Algorithms That Use Pre-Alignment
•
Input : pairwise or multiple alignment
• Obtained using standard alignment programs such as T-Coffee,
DRAWBACKS
•
the input alignment.
PRRN, or Clustal
•
• Prediction programs compute - covariation + consensus
• Successful for - reasonably conserved sequences
If there are errors in the
alignment - covariation
structure common for all the sequences
• Thermodynamic calculations included to improve accuracy
Depends on the quality of
signals will not be detected
•
The selection of single
consensus structure alternative and evolutionarily
• Requirements
unconserved structures are
1. Appropriate set of homologous sequences, similar enough to
not predicted
allow accurate alignment
2. Divergent enough to allow covariations to be detected