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Genes Cells. 2015 Oct;20(10):771-88. doi: 10.1111/gtc.12278. Epub 2015 Sep 7.

Baton pass hypothesis: successive incorporation of unconserved endogenous retroviral genes for placentation during mammalian evolution.

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Laboratory of Theriogenology and Animal Breeding, Graduate School of Agricultural and Life Science, The University of Tokyo, Tokyo, 113-8657, Japan.
Biomedical Informatics Laboratory, Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa, 259-1193, Japan.
Laboratory of Signal Transduction, Department of Cell Biology, Institute for Virus Research, Kyoto University, Kyoto, 606-8507, Japan.


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.

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