The Phylogeny of Placental Evolution Through Dynamic Integrations of Retrotransposons.

Abstract

Trophoblasts, a major constituent of the placenta, are known to express genes derived from various endogenous retroviruses (ERVs) as well as LTR retrotransposons. However, the evolutionary significance of ERV-derived genes involved in placental development has not been well characterized. In this review, we catalog the diverse morphology of placental structure among mammalian species with note of counterintuitive developments. We then detail the history of ancient placenta development with paternally expressed gene 10 (Peg10/Sirh1), Peg11/Sirh2, and Sirh7/Ldoc1 as LTR retrotransposons, followed by independent captures of ERV-env-related genes such as Syncytin-1, -2, -A, -B, -Rum1, and Fematrin-1 responsible for trophoblast cell fusion, resulting in multinucleate syncytiotrophoblast formation, and possibly morphological diversification of placentas. Because the endogenization of retroviral infections has occurred multiple times independently in different mammalian lineages, and some use the same molecules in their transcriptional activation, we speculate that ERV gene variants integrated into mammalian genomes in a locus-specific manner have replaced the genes previously responsible for cell fusion. Moreover, ERVs also work as transcriptional regulators of various genes such as interferon (IFN)-stimulated genes. The "baton pass" hypothesis suggests that evolutionary events caused by multiple successive retrotransposon integrations, possibly resulting in effective fusogenic activity, downstream gene transcription in a temporal and spatial manner, and/or increased diversity of placental structures.