Cladistic analysis of extant mustelids based on a data matrix consisting of 30 characters derived from morphological study of the head skeleton in all 23 genera, and 16 characters gleaned from the literature, yielded 75 most parsimonious trees with a consistency index of 0.487 using PAUP 3.0s. The analysis strongly supports the monophyly of both the Mephitinae (skunks) and Lutrinae (otters). The Mustelinae (weasels, martens, wolverine, etc) is probably paraphyletic, but there is some support for a monophyletic group consisting of the mustelines and the honey badger Mellivora. The Melinae (badgers) is a polyphyletic group; the badger ecomorph probably evolved independently at least three times within the Mustelidae. On consensus trees, there is a lack of resolution concerning the relationships within the Mephitinae and Lutrinae and the positions of Galictis and Mustela. These results are broadly congruent with a cladistic interpretation of Simpson's intent in his influential 1945 classification. Thus, a paraphyletic Mustelinae is consistent with Simpson's conception of a horizontal grouping, whereas the Mephitinae and Lutrinae represent vertical divergent lineages. In contrast, the cladistic status of the Melinae is not consistent with Simpsonian classificatory principles. The status of the monotypic Mellivorinae cannot be evaluated without considering its putative fossil members; however, the clustering of Mellivora with the badger Taxidea is not consistent with Simpson's scheme. Some of the more inclusive clades in the most parsimonious trees are vulnerable to minor changes to the data matrix. The fossil record is consistent with the basic outlines of the cladistic pattern and explains various ostensible biogeographic anomalies. Bootstrap analysis identified marked variation in the support for the components of the cladistic pattern.

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