Genetic recapitulation of human pre-eclampsia risk during convergent evolution of reduced placental invasiveness in eutherian mammals

Michael G. Elliot*, Bernard J. Crespi

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

21 Citations (Scopus)

Abstract

The relationship between phenotypic variation arising through individual development and phenotypic variation arising through diversification of species has long been a central question in evolutionary biology. Among humans, reduced placental invasion into endometrial tissues is associated with diseases of pregnancy, especially pre-eclampsia, and reduced placental invasiveness has also evolved, convergently, in at least 10 lineages of eutherian mammals. We tested the hypothesis that a common genetic basis underlies both reduced placental invasion arising through a developmental process in human placental disease and reduced placental invasion found as a derived trait in the diversification of Euarchontoglires (rodents, lagomorphs, tree shrews, colugos and primates). Based on whole-genome analyses across 18 taxa, we identified 1254 genes as having evolved adaptively across all three lineages exhibiting independent evolutionary transitions towards reduced placental invasion. These genes showed strong evidence of enrichment for associations with pre-eclampsia, based on genetic-association studies, gene-expression analyses and gene ontology. We further used in silico prediction to identify a subset of 199 genes that are likely targets of natural selection during transitions in placental invasiveness and which are predicted to also underlie human placental disorders. Our results indicate that abnormal ontogenies can recapitulate major phylogenetic shifts in mammalian evolution, identify new candidate genes for involvement in pre-eclampsia, imply that study of species with less-invasive placentation will provide useful insights into the regulation of placental invasion and pre-eclampsia, and recommend a novel comparative functional-evolutionary approach to the study of genetically based human disease and mammalian diversification.

Original languageEnglish
Article number20140069
Number of pages13
JournalPhilosophical Transactions of the Royal Society of London. Series B: Biological Sciences
Volume370
Issue number1663
DOIs
Publication statusPublished - 5-Mar-2015
Externally publishedYes

Keywords

  • placentation
  • pre-eclampsia
  • positive selection
  • candidate genes
  • Darwinian medicine
  • TUMOR-NECROSIS-FACTOR
  • HUMAN TROPHOBLAST
  • FACTOR-ALPHA
  • GROWTH-FACTOR
  • NITRIC-OXIDE
  • SEXUAL COHABITATION
  • REPRODUCTIVE MODE
  • SIGNALING PATHWAY
  • PIG TROPHOBLAST
  • SPIRAL ARTERIES

Fingerprint

Dive into the research topics of 'Genetic recapitulation of human pre-eclampsia risk during convergent evolution of reduced placental invasiveness in eutherian mammals'. Together they form a unique fingerprint.

Cite this