title: Genetic diversity and natural selection footprints of the glycine amidinotransferase gene in various human populations.
abstract: The glycine amidinotransferase gene (GATM) plays a vital role in energy metabolism in muscle tissues and is associated with multiple clinically important phenotypes. However, the genetic diversity of the GATM gene remains poorly understood within and between human populations. Here we analyzed the 1,000 Genomes Project data through population genetics approaches and observed significant genetic diversity across the GATM gene among various continental human populations. We observed considerable variations in GATM allele frequencies and haplotype composition among different populations. Substantial genetic differences were observed between East Asian and European populations (FST = 0.56). In addition, the frequency of a distinct major GATM haplotype in these groups was congruent with population-wide diversity at this locus. Furthermore, we identified GATM as the top differentiated gene compared to the other statin drug response-associated genes. Composite multiple analyses identified signatures of positive selection at the GATM locus, which was estimated to have occurred around 850 generations ago in European populations. As GATM catalyzes the key step of creatine biosynthesis involved in energy metabolism, we speculate that the European prehistorical demographic transition from hunter-gatherer to farming cultures was the driving force of selection that fulfilled creatine-based metabolic requirement of the populations.
authors.affiliation: Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences, Chinese academy of Sciences, Shanghai 200031, China.|Department of Biochemistry, Abdul Wali Khan University Mardan (AWKUM), Mardan, Khyber Pakhthunkhwa, Pakistan.
authors.forename: Asifullah
authors.initials: A
authors.lastname: Khan
authors.affiliation: Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences, Chinese academy of Sciences, Shanghai 200031, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Tian
authors.affiliation: Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences, Chinese academy of Sciences, Shanghai 200031, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences, Chinese academy of Sciences, Shanghai 200031, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yuan
authors.affiliation: Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences, Chinese academy of Sciences, Shanghai 200031, China.|School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China.|Collaborative Innovation Center of Genetics and Development, Shanghai 200438, China.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Xu
mesh_terms: D000579:Amidinotransferases / Q000235:genetics*; D056426:Genetic Loci; D014644:Genetic Variation; D005828:Genetics, Population; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D019655:Quantitative Trait, Heritable; D044469:Racial Groups / Q000235:genetics; D012641:Selection, Genetic
chemical_list: D000579:Amidinotransferases; C020681:glycine amidinotransferase