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The Neandertal Progesterone Receptor.

Hugo Zeberg^1,2, Janet Kelso¹, Svante Pääbo^1,3

¹Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.

Molecular Biology and Evolution

|May 22, 2020

Summary

Neandertal gene variants in the progesterone receptor (PGR) gene may enhance fertility in modern humans. These ancient alleles are linked to increased siblings and reduced pregnancy complications, explaining their prevalence.

Keywords:

Neandertals PROGINS fertility progesterone receptor

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Area of Science:

Human evolution
Reproductive biology
Genetics

Background:

Progesterone is crucial for uterine receptivity and early pregnancy maintenance.
The progesterone receptor (PGR) gene contains Neandertal introgressed haplotypes.
These Neandertal variants are common in non-African populations and linked to preterm birth.

Purpose of the Study:

To investigate the origin and functional impact of Neandertal haplotypes in the human PGR gene.
To determine the effect of these Neandertal alleles on progesterone receptor expression and reproductive success.

Main Methods:

Analysis of Neandertal genomes to characterize PGR haplotypes.
Genotyping and expression analysis in modern human populations.
Association studies with reproductive outcomes in a cohort of present-day Britons.

Main Results:

Identified two distinct Neandertal PGR haplotypes introgressed into modern humans.
Neandertal haplotype carriers exhibit higher progesterone receptor expression.
Carriers show increased number of siblings, reduced miscarriage rates, and less early pregnancy bleeding.

Conclusions:

Neandertal alleles at the PGR locus appear to confer a fertility advantage.
This reproductive benefit likely explains the high frequency of these introgressed haplotypes in non-African populations.
Ancient introgression of functional genetic variants can impact modern human reproductive health.