Abstract
The hormone progesterone is important for preparing the uterine lining for egg implantation and for maintaining the early stages of pregnancy. The gene encoding the progesterone receptor (PGR) carries introgressed Neandertal haplotypes with two missense substitutions and a mobile Alu element. These Neandertal gene variants have reached nearly 20% frequency in non-Africans and have been associated with preterm birth. Here, we show that one of the missense substitutions appears fixed in Neandertals, while the other substitution as well as the Alu insertion were polymorphic among Neandertals. We show that two Neandertal haplotypes carrying the PGR gene entered the modern human population and that present-day carriers of the Neandertal haplotypes express higher levels of the receptor. In a cohort of present-day Britons, these carriers have more siblings, fewer miscarriages, and less bleeding during early pregnancy suggesting that the Neandertal progesterone receptor alleles promote fertility. This may explain their high frequency in modern human populations.
Highlights
Progesterone is a steroid sex hormone produced by the ovaries, placenta, and adrenal glands that is involved in pregnancy, menstrual cycle, libido, and embryogenesis in placental mammals (Taraborrelli 2015)
We find that it is homozygously present in a third Neandertal genome and present in Neandertal genomes sequenced to low coverage
The Alu element is embedded in the Neandertal haplotype but we find that V660L does not fully cosegregate with Alu insertion in the 1000 Genomes data set (r2 1⁄4 0.72)
Summary
Progesterone is a steroid sex hormone produced by the ovaries, placenta, and adrenal glands that is involved in pregnancy, menstrual cycle, libido, and embryogenesis in placental mammals (Taraborrelli 2015). We find that it is homozygously present in a third Neandertal genome and present in Neandertal genomes sequenced to low coverage (supplementary table S2, Supplementary Material online). In addition to V660L, the Neandertal haplotype includes the H770H synonymous variant (rs1042839, r2 1⁄4 0.98) and the S344T missense variant (rs3740753, r2 1⁄4 0.95), both of which were polymorphic in Neandertals but do not occur in the high coverage Denisovan genome (supplementary table S2, Supplementary Material online).
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