New trends in protein sequence divergence

In an article published online in Nature, we validated the hypothesis that compensatory interactions allow most protein sequences, even the most conservative ones, to maintain the same function while diverging in sequence almost without limit.



It is clear that protein function prevents some substitutions from fixation in protein sequence. However, even if specific substitutions are forbidden in evolution, compensatory interactions between different amino acid stes may allow protein sequences to maintain a protein function while reaching a substantial level of divergence from each other in sequence. Using an approach that was first utilized to study the divergence of galaxies we show that even proteins that were predicted to have been diverging in sequence since the common ancestor of all of life are continuing to become less and less similar with time. This observation underlines the importance of understanding compensatory interactions in protein structures to be able to accurately model patterns of molecular evolution in proteins.