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

  • 3,267
    views
  • 490
    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. Ecology
    2. Evolutionary Biology
    Vendula Bohlen Šlechtová, Tomáš Dvořák ... Joerg Bohlen
    Research Article

    Eurasia has undergone substantial tectonic, geological, and climatic changes throughout the Cenozoic, primarily associated with tectonic plate collisions and a global cooling trend. The evolution of present-day biodiversity unfolded in this dynamic environment, characterised by intricate interactions of abiotic factors. However, comprehensive, large-scale reconstructions illustrating the extent of these influences are lacking. We reconstructed the evolutionary history of the freshwater fish family Nemacheilidae across Eurasia and spanning most of the Cenozoic on the base of 471 specimens representing 279 species and 37 genera plus outgroup samples. Molecular phylogeny using six genes uncovered six major clades within the family, along with numerous unresolved taxonomic issues. Dating of cladogenetic events and ancestral range estimation traced the origin of Nemacheilidae to Indochina around 48 mya. Subsequently, one branch of Nemacheilidae colonised eastern, central, and northern Asia, as well as Europe, while another branch expanded into the Burmese region, the Indian subcontinent, the Near East, and northeast Africa. These expansions were facilitated by tectonic connections, favourable climatic conditions, and orogenic processes. Conversely, aridification emerged as the primary cause of extinction events. Our study marks the first comprehensive reconstruction of the evolution of Eurasian freshwater biodiversity on a continental scale and across deep geological time.