Pathogen selection drives nonoverlapping associations between HLA loci
Pathogen selection drives nonoverlapping associations between HLA loci
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DOI：
10.1073/pnas.1304218110
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发表时间：
2013-11-26
影响因子：
11.1
通讯作者：
Gupta, Sunetra
中科院分区：
文献类型：
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作者：
Penman, Bridget S.;Ashby, Ben;Gupta, Sunetra
病原体介导的选择通常被用来解释HLA基因簇的异常多态性，但其在产生和维持HLA基因座之间的连锁不平衡中的作用尚不清楚。在这里，我们表明，病原体介导的选择可以促进HLA基因座之间的非随机关联。这些关联可能与其他群体遗传过程产生的连锁不平衡相区别，因为它们是非重叠和非随机的。在我们的框架内，免疫选择迫使病原体群体作为一组抗原性离散的菌株存在，这就驱动了HLA基因座之间的非重叠关联，通过这些基因座介导了对这些抗原的识别。我们证明了这种病原体驱动的选择的签名可以在现有的数据中观察到，并建议HLA群体结构的分析可以与实验室研究相结合，以帮助我们揭示HLA等位基因之间的功能关系。在更广泛的共同进化的背景下，我们的框架还表明，包括记忆免疫可以导致强大的循环动力学在一系列的宿主-病原体系统。
Pathogen-mediated selection is commonly invoked as an explanation for the exceptional polymorphism of the HLA gene cluster, but its role in generating and maintaining linkage disequilibrium between HLA loci is unclear. Here we show that pathogen-mediated selection can promote nonrandom associations between HLA loci. These associations may be distinguished from linkage disequilibrium generated by other population genetic processes by virtue of being nonoverlapping as well as nonrandom. Within our framework, immune selection forces the pathogen population to exist as a set of antigenically discrete strains; this then drives nonoverlapping associations between the HLA loci through which recognition of these antigens is mediated. We demonstrate that this signature of pathogen-driven selection can be observed in existing data, and propose that analyses of HLA population structure can be combined with laboratory studies to help us uncover the functional relationships between HLA alleles. In a wider coevolutionary context, our framework also shows that the inclusion of memory immunity can lead to robust cyclical dynamics across a range of host-pathogen systems.