Thermal adaptation of mRNA secondary structure: stability versus lability

Significance We demonstrate that the free energy change that occurs during folding of the secondary structures (ΔG fold ) of messenger RNAs (mRNAs) for cytosolic malate dehydrogenase varies significantly with evolutionary adaption temperature in marine mollusks. These adaptive changes in ΔG fold confer a physiologically important balance between stability and lability of secondary structure. This balance likely is of key importance in ensuring that the many functions of mRNA that depend on reversible changes in secondary structure can be conducted effectively at different species’ normal body temperatures. Synonymous changes in guanine + cytosine (G+C) content are the primary driver of adaptive change in ΔG fold ; these G+C adaptations can confer appropriate stability on the mRNAs without altering stability or function of the proteins they encode.