Document Detail

Adaptive selection of an incretin gene in Eurasian populations.
MedLine Citation:
PMID:  20978139     Owner:  NLM     Status:  MEDLINE    
Diversities in human physiology have been partially shaped by adaptation to natural environments and changing cultures. Recent genomic analyses have revealed single nucleotide polymorphisms (SNPs) that are associated with adaptations in immune responses, obvious changes in human body forms, or adaptations to extreme climates in select human populations. Here, we report that the human GIP locus was differentially selected among human populations based on the analysis of a nonsynonymous SNP (rs2291725). Comparative and functional analyses showed that the human GIP gene encodes a cryptic glucose-dependent insulinotropic polypeptide (GIP) isoform (GIP55S or GIP55G) that encompasses the SNP and is resistant to serum degradation relative to the known mature GIP peptide. Importantly, we found that GIP55G, which is encoded by the derived allele, exhibits a higher bioactivity compared with GIP55S, which is derived from the ancestral allele. Haplotype structure analysis suggests that the derived allele at rs2291725 arose to dominance in East Asians ∼8100 yr ago due to positive selection. The combined results suggested that rs2291725 represents a functional mutation and may contribute to the population genetics observation. Given that GIP signaling plays a critical role in homeostasis regulation at both the enteroinsular and enteroadipocyte axes, our study highlights the importance of understanding adaptations in energy-balance regulation in the face of the emerging diabetes and obesity epidemics.
Chia Lin Chang; James J Cai; Chiening Lo; Jorge Amigo; Jae-Il Park; Sheau Yu Teddy Hsu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-26
Journal Detail:
Title:  Genome research     Volume:  21     ISSN:  1549-5469     ISO Abbreviation:  Genome Res.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-05     Completed Date:  2011-04-21     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  9518021     Medline TA:  Genome Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  21-32     Citation Subset:  IM    
Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Chang Gung University, Kweishan, Taoyuan 333, Taiwan.
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MeSH Terms
Adaptation, Physiological*
Amino Acid Sequence
Asian Continental Ancestry Group / genetics*
Cell Line
Evolution, Molecular
Far East
Gastric Inhibitory Polypeptide / genetics*
Genetics, Population
Incretins / genetics*
Molecular Sequence Data
Polymorphism, Single Nucleotide
Protein Isoforms / genetics
Rats, Sprague-Dawley
Selection, Genetic*
Grant Support
Reg. No./Substance:
0/Incretins; 0/Protein Isoforms; 59392-49-3/Gastric Inhibitory Polypeptide

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