Sex-specific phenotypic effects and evolutionary history of an ancient polymorphic deletion of the human growth hormone receptor.

Autor: Saitou M; Department of Biological Sciences, University at Buffalo, Buffalo, NY, USA., Resendez S; Department of Biological Sciences, University at Buffalo, Buffalo, NY, USA., Pradhan AJ; Department of Chemistry, University at Buffalo, Buffalo, NY, USA., Wu F; Department of Ophthalmology, Ross Eye Institute, Jacobs School of Medicine and Biological Sciences, University at Buffalo, Buffalo, NY, USA., Lie NC; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA., Hall NJ; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA., Zhu Q; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA., Reinholdt L; The Jackson Laboratory, Bar Harbor, ME, USA., Satta Y; Department of Evolutionary Studies of Biosystems, SOKENDAI (Graduate University for Advanced Studies), Kanagawa Prefecture, Japan., Speidel L; University College London, Genetics Institute, London, UK.; The Francis Crick Institute, London, UK., Nakagome S; School of Medicine, Trinity College Dublin, Dublin, Ireland., Hanchard NA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA., Churchill G; The Jackson Laboratory, Bar Harbor, ME, USA., Lee C; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.; Precision Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, People's Republic of China., Atilla-Gokcumen GE; Department of Chemistry, University at Buffalo, Buffalo, NY, USA., Mu X; Department of Ophthalmology, Ross Eye Institute, Jacobs School of Medicine and Biological Sciences, University at Buffalo, Buffalo, NY, USA., Gokcumen O; Department of Biological Sciences, University at Buffalo, Buffalo, NY, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2021 Sep 24; Vol. 7 (39), pp. eabi4476. Date of Electronic Publication: 2021 Sep 24.
DOI: 10.1126/sciadv.abi4476
Abstrakt: The common deletion of the third exon of the growth hormone receptor gene ( GHRd3 ) in humans is associated with birth weight, growth after birth, and time of puberty. However, its evolutionary history and the molecular mechanisms through which it affects phenotypes remain unresolved. We present evidence that this deletion was nearly fixed in the ancestral population of anatomically modern humans and Neanderthals but underwent a recent adaptive reduction in frequency in East Asia. We documented that GHRd3 is associated with protection from severe malnutrition. Using a novel mouse model, we found that, under calorie restriction, Ghrd3 leads to the female-like gene expression in male livers and the disappearance of sexual dimorphism in weight. The sex- and diet-dependent effects of GHRd3 in our mouse model are consistent with a model in which the allele frequency of GHRd3 varies throughout human evolution as a response to fluctuations in resource availability.
Databáze: MEDLINE