J. Mol. Evol. 10,339-348 (1978)

Journal of Molecular Evolution © by Springer-Verlag 1978

Generalization and Simplification of the Moore-Goodman Test for Significance of Alignment Homologies Hel mut Vogel D~partement de Biochimie Macromol~laire, CNRS, F-34033 Montpellier, France

Summary. A test given by Moore and Goodman (1977) that checks the significance of a homology between protein sequences is generalized to any type of distance measure and to any classification of codon pairs or amino acids according to this measure. A normal distribution is shown to approximate satisfactorily the probability distribution underlying this test for the examples chosen, and supposedly for any distance measure. The test accordingly reduces to a simple standard procedure. Key words. Protein sequence alignments - Evolutionary divergence - Minimum mutation distance - Homologous sequences -- Significance test - Normal distribution

Moore and Goodman (1977) devised a statistic which decides whether the apparent homology of a given alignment between two amino acid sequences can be significantly attributed to evolutionary divergence (common ancestry). This method is based on a c o u n t of minimal mutation distances (MMD) between the two sequences, as compared to tabulated critical values corresponding to different confidence levels for the hypothesis of common ancestry. I propose two modifications of the method, one concerning its basic assumptions, the other its applications.

Basic Assumptions. Moore and Goodman compute their critical values by first classifying the 61 x 61 possible pairs of sense codons as to the MMD between the amino acids coded by them. The relative frequencies q(i) of the different MMD values (i) are then fed into the computer as a basis for a recursive procedure. The alignment asp ala = A D, for instance, is given a MMD 1, since there are codons of A (namely GCC, GCU) that are only one substitution step apart from codons of D (GAC, GAU). Consequently, the codon pair • G GCA A C is also assigned a distance of 1, since its mapping on amino acids yields A D" This procedure implicitly assumes common ancestry to exist, for otherwise there would be no reason to prefer GCC, GCU as codons for A to GCA, GCG in the definition of the MMD. A test that just intends to decide about common ancestry might be biased by such an assumption. 0022-2844/78/0010/0339/$ 02.00

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Generalization and simplification of the Moore-Goodman test for significant of alignment homologies.

J. Mol. Evol. 10,339-348 (1978) Journal of Molecular Evolution © by Springer-Verlag 1978 Generalization and Simplification of the Moore-Goodman Test...
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