title: Signature of positive selection of PTK6 gene in East Asian populations: a cross talk for Helicobacter pylori invasion and gastric cancer endemicity.
abstract: Analysis of natural selection events is an attractive strategy for identification of functional variants shaped by gene-environmental interactions and human adaptation. Here, we identified PTK6, a Src-related tyrosine kinase gene, underlying positive selection in East Asian populations. Interestingly, PTK6 variant showed significant correlation with gastric cancer incidences which was the highest in East Asian populations. The high prevalence of gastric cancer in East Asians was also believed to be strongly affected by Helicobacter pylori infection and dietary habit. Therefore, we speculated a competitive interaction of cancer-associated molecules for activation/reduction, where PTK6 likely plays a role through CagA-driven signaling pathway after H. pylori infection. This hypothesis was also supported by our gene expression analysis and the dating of the selective event which was estimated to be ~16,500 years ago, much later than H. pylori invasion in human 50,000 years ago. Establishment of cross talk between PTK6 and CagA by functional studies may further elucidate the underlying biology of H. pylori-mediated gastric cancer.
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: Pankaj
authors.initials: P
authors.lastname: Jha
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: Dongsheng
authors.initials: D
authors.lastname: Lu
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: Yuan
authors.initials: Y
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. xushua@picb.ac.cn.|School of Life Science and Technology, ShanghaiTec University, Shanghai, 200031, China. xushua@picb.ac.cn.|Collaborative Innovation Center of Genetics and Development, Shanghai, 200438, China. xushua@picb.ac.cn.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Xu
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics; D001208:Asia / Q000453:epidemiology; D001426:Bacterial Proteins / Q000235:genetics; D019353:Endemic Diseases; D015870:Gene Expression; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012641:Selection, Genetic; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000382:microbiology; D014774:Virulence / Q000235:genetics; D019061:src-Family Kinases / Q000235:genetics
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D009363:Neoplasm Proteins; C080866:cagA protein, Helicobacter pylori; C089510:SRMS protein, human; D011505:Protein-Tyrosine Kinases; C088375:PTK6 protein, human; D019061:src-Family Kinases
keywords: East Asian; Gastric cancer; H. pylori; Natural selection; PTK6
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