Evolutionary transcriptomics implicates new genes and pathways in human pregnancy and adverse pregnancy outcomes
- University of Chicago, United States
- Cornell University, United States
- University of Warwick, United Kingdom
- 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.
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KeyGenes, a Tool to Probe Tissue Differentiation Using a Human Fetal Transcriptional Atlas.NCBI Gene Expression Omnibus, GSE19373.
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oint analysis of microRNome and 3'-UTRome in the endometrium of rhesus monkeyNCBI Gene Expression Omnibus, GSE31041.
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Identification of gene expression changes in rabbit uterus during embryo implantationNCBI Gene Expression Omnibus, GSE76115.
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Transcriptional Complexity in Receptive and Pre-receptive Endometrium of Dairy GoatNCBI Short Read Archive, SRX958169.
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Deep sequencing of the porcine endometrial transcriptome on day 14 of pregnancyNCBI Gene Expression Omnibus, GSE43667.
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RNAseq_Scrassicaudata_uterusNCBI Short Read Archive, SRX3108600.
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Lizard 3 - uterus of the omphalo-placentaNCBI Short Read Archive, SRX498626.
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RNAseq of Lerista bougainvillii non reproductive uterusNCBI Short Read Archive, SRX2188820.
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RNAseq of Lampropholis guichenoti gravid uterusNCBI Short Read Archive, SRX2188824.
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normal chicken uterus with eggs at 40-weeksNCBI Short Read Archive, SRX180570.
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RNA-seq of Numida meleagris : adult female uterus 12 hours post-ovulationNCBI Short Read Archive, SRR5482408.
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A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stagesNCBI Gene Expression Omnibus, GSE53960.
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cDNA obtained from mRNA extracted from cows endometriumNCBI Short Read Archive, SRR1685980.
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European mouflon and Finnsheep TranscriptomeNCBI Short Read Archive, SRR7062131.
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Water buffalo gene expression atlasNCBI BioProject, PRJEB25226.
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Evolution of viviparity: Genomic and transcriptomic investigations of the transition from egg-laying to live birthChinese National GenBank: CNP0000203.https://doi.org/10.26036/CNP0000203
Article and author information
Author details
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.
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Evolutionary transcriptomics implicates new genes and pathways in human pregnancy and adverse pregnancy outcomes
eLife 10:e69584.
https://doi.org/10.7554/eLife.69584
Further reading
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A unique set of genes influences human pregnancy and birth
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- Evolutionary Biology
Lineages of rod-shaped bacteria such as Escherichia coli exhibit a temporal decline in elongation rate in a manner comparable to cellular or biological aging. The effect results from the production of asymmetrical daughters, one with a lower elongation rate, by the division of a mother cell. The slower daughter compared to the faster daughter, denoted respectively as the old and new daughters, has more aggregates of damaged proteins and fewer expressed gene products. We have examined further the degree of asymmetry by measuring the density of ribosomes between old and new daughters and between their poles. We found that ribosomes were denser in the new daughter and also in the new pole of the daughters. These ribosome patterns match the ones we previously found for expressed gene products. This outcome suggests that the asymmetry is not likely to result from properties unique to the gene expressed in our previous study, but rather from a more fundamental upstream process affecting the distribution of ribosomal abundance. Because damage aggregates and ribosomes are both more abundant at the poles of E. coli cells, we suggest that competition for space between the two could explain the reduced ribosomal density in old daughters. Using published values for aggregate sizes and the relationship between ribosomal number and elongation rates, we show that the aggregate volumes could in principle displace quantitatively the amount of ribosomes needed to reduce the elongation rate of the old daughters.
