Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Divisions of Gastroenterology and Infectious Diseases, Department of Medicine, and Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232.
Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1455-60. doi: 10.1073/pnas.1318093111. Epub 2014 Jan 13.
Helicobacter pylori is the principal cause of gastric cancer, the second leading cause of cancer mortality worldwide. However, H. pylori prevalence generally does not predict cancer incidence. To determine whether coevolution between host and pathogen influences disease risk, we examined the association between the severity of gastric lesions and patterns of genomic variation in matched human and H. pylori samples. Patients were recruited from two geographically distinct Colombian populations with significantly different incidences of gastric cancer, but virtually identical prevalence of H. pylori infection. All H. pylori isolates contained the genetic signatures of multiple ancestries, with an ancestral African cluster predominating in a low-risk, coastal population and a European cluster in a high-risk, mountain population. The human ancestry of the biopsied individuals also varied with geography, with mostly African ancestry in the coastal region (58%), and mostly Amerindian ancestry in the mountain region (67%). The interaction between the host and pathogen ancestries completely accounted for the difference in the severity of gastric lesions in the two regions of Colombia. In particular, African H. pylori ancestry was relatively benign in humans of African ancestry but was deleterious in individuals with substantial Amerindian ancestry. Thus, coevolution likely modulated disease risk, and the disruption of coevolved human and H. pylori genomes can explain the high incidence of gastric disease in the mountain population.
幽门螺杆菌是胃癌的主要病因，也是全球癌症死亡率第二高的病因。然而，幽门螺杆菌的流行率通常不能预测癌症的发病率。为了确定宿主和病原体之间的共同进化是否会影响疾病风险，我们研究了在匹配的人类和幽门螺杆菌样本中，胃病变的严重程度与基因组变异模式之间的关联。我们从两个地理位置不同的哥伦比亚人群中招募了患者，这两个人群的胃癌发病率有显著差异，但幽门螺杆菌感染的流行率几乎相同。所有幽门螺杆菌分离株都含有多种祖源的遗传特征，以非洲祖先为主的集群主要存在于低风险的沿海人群中，而以欧洲祖先为主的集群则存在于高风险的山区人群中。活检个体的人类祖源也随地理位置而变化，沿海地区主要是非洲祖源（58%），山区主要是美洲印第安人祖源（67%）。宿主和病原体祖源之间的相互作用完全解释了哥伦比亚两个地区胃病变严重程度的差异。具体来说，在具有非洲祖源的人群中，非洲幽门螺杆菌祖源相对良性，但在具有大量美洲印第安人祖源的个体中则具有危害性。因此，共同进化可能调节了疾病风险，而共同进化的人类和幽门螺杆菌基因组的破坏可以解释山区人群中胃疾病高发的原因。
