1. Evolutionary Biology
Download icon

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
Research Article
  • Cited 0
  • Views 329
  • Annotations
Cite this article as: eLife 2021;10:e69584 doi: 10.7554/eLife.69584

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.

Reviewing Editor

  1. Antonis Rokas, Vanderbilt University, United States

Publication history

  1. Received: April 20, 2021
  2. Accepted: October 7, 2021
  3. Accepted Manuscript published: October 8, 2021 (version 1)

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

  • 329
    Page views
  • 61
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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)

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

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

Further reading

    1. Evolutionary Biology
    2. Microbiology and Infectious Disease
    Debapriyo Chakraborty
    Insight

    The repeated emergence of similar variants of influenza virus is linked to interactions between the virus’s RNA segments.

    1. Evolutionary Biology
    2. Genetics and Genomics
    Gabriela Santos-Rodriguez et al.
    Research Article Updated

    Many primate genes produce circular RNAs (circRNAs). However, the extent of circRNA conservation between closely related species remains unclear. By comparing tissue-specific transcriptomes across over 70 million years of primate evolution, we identify that within 3 million years circRNA expression profiles diverged such that they are more related to species identity than organ type. However, our analysis also revealed a subset of circRNAs with conserved neural expression across tens of millions of years of evolution. By comparing to species-specific circRNAs, we identified that the downstream intron of the conserved circRNAs display a dramatic lengthening during evolution due to the insertion of novel retrotransposons. Our work provides comparative analyses of the mechanisms promoting circRNAs to generate increased transcriptomic complexity in primates.