Similarity and Congruence as Criteria for Molecular Homology
Authors: David Mindell
Journal: Molecular Biology and Evolution (1991)

Homology" denotes a hypothesis of correspondence between features due to common ancestry.The term was originally coined for morphologists in 1848 by Richard Owen and has been logically extended to molecular sequence features ever since such features have been identified and compared across taxa (e.g., see Watson and Kendrew 196 1; Fitch 1966 Fitch , 1970)).In morphological studies, two primary criteria used for recognizing homologous features are an ( 1) "essential sameness," or similarity, in composition, function, structural position, or ontogenetic origin (Remane 1956;Riedl 1978) and (2) congruence with other postulated homologies, as determined by their agreement in supporting the same phylogenetic relationships (e.g., see Wiley 1975 ) .Patterson ( 1988, p. 603) reviewed molecular homology and techniques for its assessment and concluded that "in morphology the congruence test is decisive in separating homology and nonhomology, whereas with molecular sequence data similarity is the decisive test."Reflecting this view, he has described molecular homology as "a statistical concept" (Patterson 1987, p. 9 ).In the present note I make the points that molecular homology should not and need not be reliant on the single criterion of similarity and that use of a congruence criterion is desirable, feasible, and consistent with current phylogenetics practice.Historically, strategies for molecular homology assessment, or sequence alignment, have either maximized matches for nucleic (or amino) acids (Needleman and Wunsch 1970) or minimized the number of substitution, insertion, or deletion events needed to make two molecular sequences equivalent (Sellers 1974).Both seek to maximize the property of identical nucleotide bases at aligned positions and use a similarity criterion.Traditionally, no congruence criterion (phylogenetic agreement with other postulated homologies) has been used.When only two sequences are to be aligned, the choices to be made concern (a) the relative costs (penalties) to be assigned for various substitution and gap events, and (b) for some algorithms, the size of the "window" or subsequence lengths to be compared for matching.When more than two sequences are to be aligned, two different approaches may be taken: ( 1) all species sequences may be treated equally (simultaneously) in seeking maximal matching across all base positions for all taxa, or (2) a phylogenetic hypothesis may, be used to guide the order of sequence input.The second approach is more appropriate for purposes of inferring evolutionary history.Because the relationship of homology for features in different taxa denotes their shared inheritance from a common ancestor, homology may be defined on the basis of continuity of information (Van Valen 1982).This information is, of course, primarily genetic, and the continuity is provided by genealogy (see Roth 1988 ).Thus, species sequences should be aligned in descending order of phylogenetic relationship ( phylogenetic weighting of alignments), to whatever extent possible, to maintain the genealogical basis for homology assessment (Mindell 199 1) .In practice, the need for phylogenetic weighting is demonstrated by different phylogenetic tree topologies arising from different orders of input for species sequences in multiple alignment bouts, with I.