title: Baton pass hypothesis: successive incorporation of unconserved endogenous retroviral genes for placentation during mammalian evolution.
abstract: It is well accepted that numerous RNAs derived from endogenous retroviruses (ERVs) are expressed in mammalian reproductive structures, particularly in the uterus, trophoblast, and placenta. Syncytin 1 and syncytin 2 in humans and syncytin A and syncytin B in mice are membrane proteins originating from Env genes of ERVs. These ERVs are involved in the fusion of trophoblast cells, resulting in multinucleated syncytiotrophoblast formation. Evidence accumulated indicates that syncytin-like fusogenic proteins are expressed in the placenta of rabbits, dogs/cats, ruminant ungulates, tenrecs, and opossums. The syncytin genes so far characterized are known to be endogenized to the host genome only within the past 12-80 million years, more recently than the appearance of mammalian placentas, estimated to be 160-180 million years ago. We speculate that ERVs including syncytin-like gene variants integrated into mammalian genomes in a locus-specific manner have replaced the genes previously responsible for cell fusion. We therefore propose the 'baton pass' hypothesis, in which multiple successive ERV variants 'take over' cell-fusion roles, resulting in increased trophoblast cell fusion, morphological variations in placental structures, and enhanced reproductive success in placental mammals.
authors.affiliation: Laboratory of Theriogenology and Animal Breeding, Graduate School of Agricultural and Life Science, The University of Tokyo, Tokyo, 113-8657, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Imakawa
authors.affiliation: Biomedical Informatics Laboratory, Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: So
authors.initials: S
authors.lastname: Nakagawa
authors.affiliation: Laboratory of Signal Transduction, Department of Cell Biology, Institute for Virus Research, Kyoto University, Kyoto, 606-8507, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Miyazawa
mesh_terms: D000818:Animals; D002459:Cell Fusion; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D005260:Female; D015686:Gene Products, env / Q000502:physiology; D005814:Genes, Viral; D006801:Humans; D008322:Mammals / Q000235:genetics* / Q000378:metabolism*; D010920:Placenta / Q000033:anatomy & histology / Q000378:metabolism / Q000821:virology; D010929:Placentation; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000502:physiology
chemical_list: D015686:Gene Products, env; D011257:Pregnancy Proteins; C405335:syncytin