BiAlign

BiAlign models the incongruent evolution of RNA sequence and secondary structure by quantifying mismatches between sequence homology and structural homology.

Key Features:

• Bi-Alignments framework: Implements bi-alignments as superpositions of two distinct alignments, one capturing sequence homology and the other capturing structural homology.
• 4-Way alignment integration: Under natural assumptions about scoring functions, represents bi-alignments as a special case of 4-way alignments and measures incongruencies as insertions or deletions (indels) between the two alignment copies.
• Evolutionary insight: Models sequence and structural homology simultaneously to identify cases where secondary structure is conserved despite sequence divergence, including non-homologous base pairing.
• Database survey support: Preliminary analyses of the Rfam database indicate that incongruent evolution of RNAs is a notable phenomenon.

Scientific Applications:

• Structural conservation analysis: Detects conserved RNA secondary structure across diverse sequences that lack positional correspondence.
• Selective pressure inference: Separates selective pressures acting on sequence versus structure to study their independent effects on RNA evolution.
• Non-homologous base pairing exploration: Investigates non-homologous base pairing and its implications for RNA function and evolution.

Methodology:

Performs a dual-alignment approach that simultaneously models sequence and structural homologies and integrates these alignments into a 4-way alignment framework to capture and quantify evolutionary incongruencies.