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
Gene duplication drives evolution by providing raw material for proteins with novel functions. An influential hypothesis by Ohno (1970) posits that gene duplication helps genes tolerate new mutations and thus facilitates the evolution of new phenotypes. Competing hypotheses argue that deleterious mutations will usually inactivate gene duplicates too rapidly for Ohno’s hypothesis to work. We experimentally tested Ohno’s hypothesis by evolving one or exactly two copies of a gene encoding a fluorescent protein in Escherichia coli through several rounds of mutation and selection. We analyzed the genotypic and phenotypic evolutionary dynamics of the evolving populations through high-throughput DNA sequencing, biochemical assays, and engineering of selected variants. In support of Ohno’s hypothesis, populations carrying two gene copies displayed higher mutational robustness than those carrying a single gene copy. Consequently, the double-copy populations experienced relaxed purifying selection, evolved higher phenotypic and genetic diversity, carried more mutations and accumulated combinations of key beneficial mutations earlier. However, their phenotypic evolution was not accelerated, possibly because one gene copy rapidly became inactivated by deleterious mutations. Our work provides an experimental platform to test models of evolution by gene duplication, and it supports alternatives to Ohno’s hypothesis that point to the importance of gene dosage.
