Protein
sequences are composed of a 20 aa alphabet determined by 61 degenerate codons. When the DNA sequences are
translated into 21 different types of codons (20 aa and a terminator), the
information is sharpened up considerably. The 'wrong-frame' information is
discarded, and third-base degeneracies are consolidated. All in all, the signal-to-noise
ratio is greatly improved for the specific purpose of identifying protein
relatives. It is accepted that convergence phenomena in aa sequences are very
rare and thus aa similarity almost always means homology. Furthermore, aa
sequences may still show a similarity derived from common folding patterns and
function of the proteins, even while their coding DNA sequences might have
strongly diverged due to other selective pressures existent at the genome
level (e.g., G+C pressure, preferential usage of synonymous codons, etc.).
Protein evolution is governed by the constraint of maintaining a
characteristic fold which enables some function. Thus, it is possible to infer
relationships between proteins that last shared a common ancestor 1-2.5 billion
years ago by conducting protein searches, doubling the lookback time obtained
performing DNA database searches.