title: Functional insight into Maelstrom in the germline piRNA pathway: a unique domain homologous to the DnaQ-H 3'-5' exonuclease, its lineage-specific expansion/loss and evolutionarily active site switch.
abstract: Maelstrom (MAEL) plays a crucial role in a recently-discovered piRNA pathway; however its specific function remains unknown. Here a novel MAEL-specific domain characterized by a set of conserved residues (Glu-His-His-Cys-His-Cys, EHHCHC) was identified in a broad range of species including vertebrates, sea squirts, insects, nematodes, and protists. It exhibits ancient lineage-specific expansions in several species, however, appears to be lost in all examined teleost fish species. Functional involvement of MAEL domains in DNA- and RNA-related processes was further revealed by its association with HMG, SR-25-like and HDAC_interact domains. A distant similarity to the DnaQ-H 3'-5' exonuclease family with the RNase H fold was discovered based on the evidence that all MAEL domains adopt the canonical RNase H fold; and several protist MAEL domains contain the conserved 3'-5' exonuclease active site residues (Asp-Glu-Asp-His-Asp, DEDHD). This evolutionary link together with structural examinations leads to a hypothesis that MAEL domains may have a potential nuclease activity or RNA-binding ability that may be implicated in piRNA biogenesis. The observed transition of two sets of characteristic residues between the ancestral DnaQ-H and the descendent MAEL domains may suggest a new mode for protein function evolution called "active site switch", in which the protist MAEL homologues are the likely evolutionary intermediates due to harboring the specific characteristics of both 3'-5' exonuclease and MAEL domains.
authors.affiliation: Department of Biology, Centre for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, Ontario, Canada. dzhan033@uottawa.ca
authors.forename: Dapeng
authors.initials: D
authors.lastname: Zhang
authors.forename: Huiling
authors.initials: H
authors.lastname: Xiong
authors.forename: Jufang
authors.initials: J
authors.lastname: Shan
authors.forename: Xuhua
authors.initials: X
authors.lastname: Xia
authors.forename: Vance L
authors.initials: VL
authors.lastname: Trudeau
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D019143:Evolution, Molecular; D005092:Exonucleases / Q000737:chemistry*; D005854:Germ Cells / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism*; D016914:Ribonuclease H / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
chemical_list: D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D005092:Exonucleases; D016914:Ribonuclease H