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Fitch, W. M. (Dept. Physiological Chetn., U. Wisconsin, Madison 53706) 1970. Distinguishing homologous from analogous proteins. Syst. Zool., 19:99–113.—This work provides a means by which it is possible to determine whether two groups of related proteins have a common ancestor or are of independent origin. A set of 16 random amino acid sequences were shown to be unrelated by this method. A set of 16 real but presumably unrelated proteins gave a similar result. A set of 24 model proteins which was composed of two independently evolving groups, converging toward the same chemical goal, was correctly shown to be convergently related, with the probability that the result was due to chance being <10−21. A set of 24 cytochromes composed of 5 fungi and 19 metazoans was shown to be divergently related, with the probability that the result was due to chance being < 10−9. A process was described which leads to the absolute minimum of nucleotide replacements required to account for the divergent descent of a set of genes given a particular topology for the tree depicting their ancestral relations. It was also shown that the convergent processes could realistically lead to amino acid sequences which would produce positive tests for relatedness, not only by a chemical criterion, but by a genetic (nucleotide sequence) criterion as well. Finally, a realistic case is indicated where truly homologous traits, behaving in a perfectly expectable way, may nevertheless lead to a ludicrous phylogeny.