The origin of the genetic code cannot be studied using measurements based on the PAM matrix because this matrix reflects the code itself, making any such analyses tautologous

Freeland et al. (Mol. Biol. Evol. 2000a, 17, 511-518) have recently used a transformation of the PAM 74-100 matrix to study the level of optimization reached during genetic code origin. Since the PAM matrix counts the amino a cid substitutions that occurred in families of homologous proteins during m olecular evolution and as this process is mediated by the genetic code stru cture itself, it could be that the influence of the code on this matrix is such as to make any conclusion insignificant. As will be shown in the prese nt paper, the transformation of the PAM matrix is affected in a non-margina l way by the organization of the genetic code and, thus, renders the analys is of Freeland et al. tautologous. Although, under the hypothesis of a high ly optimized genetic code, some correlations may be expected between a meas urement of similarity between amino acids and the genetic code structure, n o certain conclusions can be drawn for the measurement used by Freeland et al. (C) 2001 Academic Press.