1. Developmental Biology
  2. Evolutionary Biology

Gene expression phylogenies and ancestral transcriptome reconstruction resolves major transitions in the origins of pregnancy

  1. Katelyn Mika
  2. Camilla M Whittington
  3. Bronwyn M McAllan
  4. Vincent J Lynch  Is a corresponding author
  1. University of Chicago, United States
  2. University of Sydney, Australia
  3. University at Buffalo, State University of New York, United States
https://doi.org/10.7554/eLife.74297
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  1. Katelyn Mika
  2. Camilla M Whittington
  3. Bronwyn M McAllan
  4. Vincent J Lynch
(2022)
Gene expression phylogenies and ancestral transcriptome reconstruction resolves major transitions in the origins of pregnancy
eLife 11:e74297.
https://doi.org/10.7554/eLife.74297
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Abstract

Structural and physiological changes in the female reproductive system underlie the origins of pregnancy in multiple vertebrate lineages. In mammals, the glandular portion of the lower reproductive tract has transformed into a structure specialized for supporting fetal development. These specializations range from relatively simple maternal nutrient provisioning in egg-laying monotremes to an elaborate suite of traits that support intimate maternal-fetal interactions in Eutherians. Among these traits are the maternal decidua and fetal component of the placenta, but there is considerable uncertainty about how these structures evolved. Previously we showed that changes in uterine gene expression contributes to several evolutionary innovations during the origins of pregnancy (Marinic, Mika, and Lynch 2021). Here we reconstruct the evolution of entire transcriptomes ('ancestral transcriptome reconstruction') and show that maternal gene expression profiles are correlated with degree of placental invasion. These results indicate that an epitheliochorial-like placenta evolved early in the mammalian stem-lineage and that the ancestor of Eutherians had a hemochorial placenta, and suggest maternal control of placental invasiveness. These data resolve major transitions in the evolution of pregnancy and indicate that ancestral transcriptome reconstruction can be used to study the function of ancestral cell, tissue, and organ systems.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 2, 3 and 5.

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Author details

  1. Katelyn Mika

    Department of Human Genetics, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2170-9364

  2. Camilla M Whittington

    School of Life and Environmental Sciences, University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5765-9699

  3. Bronwyn M McAllan

    School of Life and Environmental Sciences, University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.

  4. Vincent J Lynch

    Department of Biological Sciences, University at Buffalo, State University of New York, Buffalo, United States
    For correspondence
    vjlynch@buffalo.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5311-3824

Funding

March of Dimes Foundation

  • Vincent J Lynch

Burroughs Wellcome Fund (1013760)

  • Vincent J Lynch

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2022, Mika et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Katelyn Mika
  2. Camilla M Whittington
  3. Bronwyn M McAllan
  4. Vincent J Lynch
(2022)
Gene expression phylogenies and ancestral transcriptome reconstruction resolves major transitions in the origins of pregnancy
eLife 11:e74297.
https://doi.org/10.7554/eLife.74297

Share this article

https://doi.org/10.7554/eLife.74297

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Further reading

    1. Evolutionary Biology
    2. Genetics and Genomics

    Evolutionary transcriptomics implicates HAND2 in the origins of implantation and regulation of gestation length

    Mirna Marinić, Katelyn Mika ... Vincent J Lynch
    Research Article Updated

    The developmental origins and evolutionary histories of cell types, tissues, and organs contribute to the ways in which their dysfunction produces disease. In mammals, the nature, development and evolution of maternal-fetal interactions likely influence diseases of pregnancy. Here we show genes that evolved expression at the maternal-fetal interface in Eutherian mammals play essential roles in the evolution of pregnancy and are associated with immunological disorders and preterm birth. Among these genes is HAND2, a transcription factor that suppresses estrogen signaling, a Eutherian innovation allowing blastocyst implantation. We found dynamic HAND2 expression in the decidua throughout the menstrual cycle and pregnancy, gradually decreasing to a low at term. HAND2 regulates a distinct set of genes in endometrial stromal fibroblasts including IL15, a cytokine also exhibiting dynamic expression throughout the menstrual cycle and gestation, promoting migration of natural killer cells and extravillous cytotrophoblasts. We demonstrate that HAND2 promoter loops to an enhancer containing SNPs implicated in birth weight and gestation length regulation. Collectively, these data connect HAND2 expression at the maternal-fetal interface with evolution of implantation and gestational regulation, and preterm birth.