Evolutionary transcriptomics implicates new genes and pathways in human pregnancy and adverse pregnancy outcomes

  1. Katelyn Mika
  2. Mirna Marinić
  3. Manvendra Singh
  4. Joanne Muter
  5. Jan Joris Brosens
  6. Vincent J Lynch  Is a corresponding author
  1. University of Chicago, United States
  2. Cornell University, United States
  3. University of Warwick, United Kingdom
  4. University at Buffalo, United States

Abstract

Evolutionary changes in the anatomy and physiology of the female reproductive system underlie the origins and diversification of pregnancy in Eutherian ('Placental') mammals. This developmental and evolutionary history constrains normal physiological functions and biases the ways in which dysfunction contributes to reproductive trait diseases and adverse pregnancy outcomes. Here, we show that gene expression changes in the human endometrium during pregnancy are associated with the evolution of human-specific traits and pathologies of pregnancy. We found that hundreds of genes gained or lost endometrial expression in the human lineage. Among these are genes that may contribute to human-specific maternal-fetal communication (HTR2B) and maternal-fetal immunotolerance (PDCD1LG2) systems, as well as vascular remodeling and deep placental invasion (CORIN). These data suggest that explicit evolutionary studies of anatomical systems complement traditional methods for characterizing the genetic architecture of disease. We also anticipate our results will advance the emerging synthesis of evolution and medicine ('evolutionary medicine') and be a starting point for more sophisticated studies of the maternal-fetal interface. Furthermore, the gene expression changes we identified may contribute to the development of diagnostics and interventions for adverse pregnancy outcomes.

Data availability

All gene expression data analysed during this study are publicly available, accession numbers of given in Figure 1 - source data 1.

The following previously published data sets were used

Article and author information

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. Mirna Marinić

    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:" 0000-0002-7037-8389
  3. Manvendra Singh

    Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Joanne Muter

    Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Jan Joris Brosens

    Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0116-9329
  6. Vincent J Lynch

    Department of Biological Sciences, University at Buffalo, 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 (Prematurity Research Center)

  • Vincent J Lynch

Burroughs Wellcome Fund (1013760)

  • Vincent J Lynch

Wellcome Trust (212233/Z/18/Z)

  • Jan Joris Brosens

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

Copyright

© 2021, 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.

Metrics

  • 3,283
    views
  • 494
    downloads
  • 29
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Katelyn Mika
  2. Mirna Marinić
  3. Manvendra Singh
  4. Joanne Muter
  5. Jan Joris Brosens
  6. Vincent J Lynch
(2021)
Evolutionary transcriptomics implicates new genes and pathways in human pregnancy and adverse pregnancy outcomes
eLife 10:e69584.
https://doi.org/10.7554/eLife.69584

Share this article

https://doi.org/10.7554/eLife.69584

Further reading

  1. A unique set of genes influences human pregnancy and birth

    1. Evolutionary Biology
    Nagatoshi Machii, Ryo Hatashima ... Masato Nikaido
    Research Article

    Cichlid fishes inhabiting the East African Great Lakes, Victoria, Malawi, and Tanganyika, are textbook examples of parallel evolution, as they have acquired similar traits independently in each of the three lakes during the process of adaptive radiation. In particular, ‘hypertrophied lip’ has been highlighted as a prominent example of parallel evolution. However, the underlying molecular mechanisms remain poorly understood. In this study, we conducted an integrated comparative analysis between the hypertrophied and normal lips of cichlids across three lakes based on histology, proteomics, and transcriptomics. Histological and proteomic analyses revealed that the hypertrophied lips were characterized by enlargement of the proteoglycan-rich layer, in which versican and periostin proteins were abundant. Transcriptome analysis revealed that the expression of extracellular matrix-related genes, including collagens, glycoproteins, and proteoglycans, was higher in hypertrophied lips, regardless of their phylogenetic relationships. In addition, the genes in Wnt signaling pathway, which is involved in promoting proteoglycan expression, was highly expressed in both the juvenile and adult stages of hypertrophied lips. Our comprehensive analyses showed that hypertrophied lips of the three different phylogenetic origins can be explained by similar proteomic and transcriptomic profiles, which may provide important clues into the molecular mechanisms underlying phenotypic parallelisms in East African cichlids.