Convergent Evolution in a Murine Intestinal Parasite Rapidly Created the TGM Family of Molecular Mimics to Suppress the Host Immune Response

The Transforming Growth Factor-β mimic (TGM) multigene family was recently discovered in the murine intestinal parasite Heligmosomoides polygyrus. This family was shaped by an atypical set of organismal and molecular evolutionary mechanisms along its path through the adaptive landscape. The relevant mechanisms are mimicry, convergence, exon modularity, new gene origination, and gene family neofunctionalization. We begin this review with a description of the TGM family and then address two evolutionary questions: “Why were TGM proteins needed for parasite survival” and “when did the TGM family originate”? For the former, we provide a likely answer, and for the latter, we identify multiple TGM building blocks in the ruminant intestinal parasite Haemonchus contortus. We close by identifying avenues for future investigation: new biochemical data to assign functions to more family members as well as new sequenced genomes in the Trichostrongyloidea superfamily and the Heligmosomoides genus to clarify TGM origins and expansion. Continued study of TGM proteins will generate increased knowledge of Transforming Growth Factor-β signaling, host–parasite interactions, and metazoan evolutionary mechanisms.