Searching for frameshift evolutionary relationships between protein sequence families

The protein sequence database was analyzed for evidence that some distinct sequence families might be distantly related in evolution by changes in fra me of translation. Sequences were compared using special amino acid substit ution matrices for the alternate frames of translation, The statistical sig nificance of alignment scores were computed in the true database and shuffl ed versions of the database that preserve any potential codon bias, The com parison of results from these two databases provides a very sensitive metho d for detecting remote relationships. We find a weak but measurable related ness within the database as a whole, supporting the notion that some protei ns may have evolved from others through changes in frame of translation. We also quantify residual homology in the ordinary sense within a database of generally unrelated sequences. Proteins 1999;37: 278-283. (C) 1999 (C) Wil ey-Liss, Inc.