An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing
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Plunkett-2011-An Evolutionary Geno.pdf
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Author(s)
Plunkett, Jevon
Doniger, Scott
Orabona, Guilherme
Morgan, Thomas
Haataja, Ritva
Hallman, Mikko
Puttonen, Hilkka
Menon, Ramkumar
Kuczynski, Edward
Norwitz, Errol
Date Issued
April 2011
Journal
PLoS Genetics
Publisher
Public Library of Science
Citation
Plunkett, Jevon et al. “An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing.” Ed. Gregory S. Barsh. PLoS Genetics 7 (2011): e1001365.
Version
Final published version
Abstract
Coordination of fetal maturation with birth timing is essential for mammalian reproduction. In humans, preterm birth is a disorder of profound global health significance. The signals initiating parturition in humans have remained elusive, due to divergence in physiological mechanisms between humans and model organisms typically studied. Because of relatively large human head size and narrow birth canal cross-sectional area compared to other primates, we hypothesized that genes involved in parturition would display accelerated evolution along the human and/or higher primate phylogenetic lineages to decrease the length of gestation and promote delivery of a smaller fetus that transits the birth canal more readily. Further, we tested whether current variation in such accelerated genes contributes to preterm birth risk. Evidence from allometric scaling of gestational age suggests human gestation has been shortened relative to other primates. Consistent with our hypothesis, many genes involved in reproduction show human acceleration in their coding or adjacent noncoding regions. We screened >8,400 SNPs in 150 human accelerated genes in 165 Finnish preterm and 163 control mothers for association with preterm birth. In this cohort, the most significant association was in FSHR, and 8 of the 10 most significant SNPs were in this gene. Further evidence for association of a linkage disequilibrium block of SNPs in FSHR, rs11686474, rs11680730, rs12473870, and rs1247381 was found in African Americans. By considering human acceleration, we identified a novel gene that may be associated with preterm birth, FSHR. We anticipate other human accelerated genes will similarly be associated with preterm birth risk and elucidate essential pathways for human parturition.
MIT Department
Broad Institute of MIT and Harvard
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DOI of Published Version
https://doi.org/10.1371/journal.pgen.1001365
