= Compensatory base change
A <compensatory base change> is a nucleotide change that offsets the effect of a change at an interacting nucleotide position, often by restoring compatible <base pairing>. In a simple <RNA> example, a canonical G–C <base pair> becomes A–C after one substitution and A–U after a second. The final sequence differs from the original while recovering canonical <Watson-Crick base pairing>.
This supplies a functional test of a proposed RNA interaction. Compare the original sequences, each altered partner separately and the pair carrying both changes. If the single changes impair the readout while the matched double change restores it, that pattern supports a pairing-dependent explanation. Recovery need not be complete, and restoring complementarity does not ensure that every other molecular interaction is restored.
A 1986 experiment tested recognition of a <splice donor site> by <U1 small nuclear RNA>. Researchers introduced altered adenovirus E1A and human U1 genes into <HeLa> <cells>, then examined whether complementary changes in U1 rescued splicing defects. Rescue was efficient for the tested change at position $+5$ of one donor but very weak for a change at position $+3$ of another.<A compensatory base change in U1 snRNA suppresses a 5′ splice site mutation by Y. Zhuang and A. M. Weiner>[Abstract, co-transfection comparison and contrasting +5/+3 outcomes]{ref} The result supported a required <base pairing> interaction while showing that complementarity alone was insufficient for normal <RNA splicing>.
Changes observed across related sequences can also suggest conserved pairing. However, shared ancestry and other sequence constraints can produce correlated changes. A designed rescue comparison tests a more specific functional prediction; neither correlation nor one successful rescue establishes every detail of the molecular contact geometry.
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