With the availability of high numbers of genomic sequences it becomes feasible to analyze such sequences for "coevolving residues". The effectiveness of this approach results from the fact that a mutation in position "i" of a protein is more likely to be associated with a mutation in position "j" than with a back-mutation in "i" if both positions are functionally coupled (e.g. by taking part in an enzymatic domain, or by being adjacent in a folded protein, or even by being adjacent in an oligomer of that protein).