Natural Selection Has Differentiated the Progesterone Receptor among Human Populations.
Am J Hum Genet
; 103(1): 45-57, 2018 07 05.
Article
em En
| MEDLINE
| ID: mdl-29937092
ABSTRACT
The progesterone receptor (PGR) plays a central role in maintaining pregnancy and is significantly associated with medical conditions such as preterm birth that affects 12.6% of all the births in U.S. PGR has been evolving rapidly since the common ancestor of human and chimpanzee, and we herein investigated evolutionary dynamics of PGR during recent human migration and population differentiation. Our study revealed substantial population differentiation at the PGR locus driven by natural selection, where very recent positive selection in East Asians has substantially decreased its genetic diversity by nearly fixing evolutionarily novel alleles. On the contrary, in European populations, the PGR locus has been promoted to a highly polymorphic state likely due to balancing selection. Integrating transcriptome data across multiple tissue types together with large-scale genome-wide association data for preterm birth, our study demonstrated the consequence of the selection event in East Asians on remodeling PGR expression specifically in the ovary and determined a significant association of early spontaneous preterm birth with the evolutionarily selected variants. To reconstruct its evolutionary trajectory on the human lineage, we observed substantial differentiation between modern and archaic humans at the PGR locus, including fixation of a deleterious missense allele in the Neanderthal genome that was later introgressed in modern human populations. Taken together, our study revealed substantial evolutionary innovation in PGR even during very recent human evolution, and its different forms among human populations likely result in differential susceptibility to progesterone-associated disease conditions including preterm birth.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Seleção Genética
/
Receptores de Progesterona
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Polimorfismo de Nucleotídeo Único
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Am J Hum Genet
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos