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Signature of positive selection of PTK6 gene in East Asian populations: a cross talk for Helicobacter pylori invasion and gastric cancer endemicity

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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.

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Acknowledgments

The authors thank the 1000 Genomes Project Consortium and GLOBOCAN 2008 (WHO) for providing data resources to public research. Funding: This study was funded by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13040100), by the National Science Foundation of China (NSFC) grants (91331204; 31171218; 31301083). P.J. was supported by International Young Scientist Fellowship of Chinese Academy of Sciences (2011Y2SB10). S.X. is Max Planck Independent Research Group Leader and member of CAS Youth Innovation Promotion Association. S.X. also gratefully acknowledges the support of the National Program for Top-notch Young Innovative Talents of The “Wanren Jihua” Project.  The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflict of interest

PJ declares that he has no conflict of interest. DL declares that she has no conflict of interest. YY declares that she has no conflict of interest. SX declares that he has no conflict of interest.

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This article does not contain any studies with human participants performed by any of the authors.

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Authors and Affiliations

  1. 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

    Pankaj Jha, Dongsheng Lu, Yuan Yuan & Shuhua Xu

  2. School of Life Science and Technology, ShanghaiTec University, Shanghai, 200031, China

    Shuhua Xu

  3. Collaborative Innovation Center of Genetics and Development, Shanghai, 200438, China

    Shuhua Xu

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  1. Pankaj Jha
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  2. Dongsheng Lu
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Correspondence to Shuhua Xu.

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Communicated by S. Hohmann.

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Jha, P., Lu, D., Yuan, Y. et al. Signature of positive selection of PTK6 gene in East Asian populations: a cross talk for Helicobacter pylori invasion and gastric cancer endemicity. Mol Genet Genomics 290, 1741–1752 (2015). https://doi.org/10.1007/s00438-015-1032-8

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