Marsupials and Eutherians reunited: genetic evidence for the Theria hypothesis of mammalian evolution

The three living monophyletic divisions of Class Mammalia are the Protother ia (monotremes), Metatheria (marsupials), and Eutheria ('placental' mammals ). Determining the sister relationships among these three groups is the mos t fundamental question in mammalian evolution. Phylogenetic comparison of t hese mammals by either anatomy or mitochondrial DNA has resulted in two con flicting hypotheses, Theria and Marsupionta, and has fueled a "genes versus morphology" controversy. We have cloned and analyzed a large nuclear gene, the mannose 6-phosphate/ insulin-like growth factor II receptor (M6P/IGF2R ), from representatives of all three mammalian groups, including platypus, echidna, opossum, wallaby, hedgehog, mouse, rat, rabbit, cow, pig, bat, tre e shrew, colugo, ringtail lemur, and human. Statistical analysis of this nu clear gene unambiguously supports the morphology-based Theria hypothesis th at excludes monotremes from a clade of marsupials and eutherians. The M6P/I GF2R was also able to resolve the finer structure of the eutherian mammalia n family tree. In particular, our analyses support sister group relationshi ps between lagomorphs: and rodents, and between the primates and Dermoptera . Statistical support for the grouping of the hedgehog with Feruungulata an d Chiroptera was also strong.