title: Ancient transposable elements transformed the uterine regulatory landscape and transcriptome during the evolution of mammalian pregnancy.
abstract: A major challenge in biology is determining how evolutionarily novel characters originate; however, mechanistic explanations for the origin of new characters are almost completely unknown. The evolution of pregnancy is an excellent system in which to study the origin of novelties because mammals preserve stages in the transition from egg laying to live birth. To determine the molecular bases of this transition, we characterized the pregnant/gravid uterine transcriptome from tetrapods to trace the evolutionary history of uterine gene expression. We show that thousands of genes evolved endometrial expression during the origins of mammalian pregnancy, including genes that mediate maternal-fetal communication and immunotolerance. Furthermore, thousands of cis-regulatory elements that mediate decidualization and cell-type identity in decidualized stromal cells are derived from ancient mammalian transposable elements (TEs). Our results indicate that one of the defining mammalian novelties evolved from DNA sequences derived from ancient mammalian TEs co-opted into hormone-responsive regulatory elements distributed throughout the genome.
authors: Department of Human Genetics, The University of Chicago, 920 East 58(th) Street, CLSC 319C, Chicago, IL 60637, USA. Electronic address: vjlynch@uchicago.edu.
authors: Vincent J
authors: VJ
authors: Lynch
authors: Yale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511, USA.
authors: Mauris C
authors: MC
authors: Nnamani
authors: Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors: Aurélie
authors: A
authors: Kapusta
authors: Yale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511, USA.
authors: Kathryn
authors: K
authors: Brayer
authors: Yale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511, USA.
authors: Silvia L
authors: SL
authors: Plaza
authors: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors: Erik C
authors: EC
authors: Mazur
authors: Yale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511, USA.
authors: Deena
authors: D
authors: Emera
authors: Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors: Shehzad Z
authors: SZ
authors: Sheikh
authors: The Robinson Institute, School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
authors: Frank
authors: F
authors: Grützner
authors: Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Feodor Lynen Strasse 25, 81377 Munich, Germany.
authors: Stefan
authors: S
authors: Bauersachs
authors: Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Feodor Lynen Strasse 25, 81377 Munich, Germany.
authors: Alexander
authors: A
authors: Graf
authors: Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27705, USA.
authors: Steven L
authors: SL
authors: Young
authors: Department of Human Genetics, The University of Chicago, 920 East 58(th) Street, CLSC 319C, Chicago, IL 60637, USA.
authors: Jason D
authors: JD
authors: Lieb
authors: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, USA.
authors: Francesco J
authors: FJ
authors: DeMayo
authors: Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors: Cédric
authors: C
authors: Feschotte
authors: Yale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511, USA.
authors: Günter P
authors: GP
authors: Wagner
mesh_terms: D000818:Animals; D005075:Biological Evolution; D004251:DNA Transposable Elements / Q000235:genetics*; D005260:Female; D008322:Mammals; D008969:Molecular Sequence Data; D011247:Pregnancy; D059467:Transcriptome / Q000235:genetics; D014599:Uterus / Q000378:metabolism*
chemical_list: D004251:DNA Transposable Elements
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