Small-scale spatial variation in infection risk shapes the evolution of a Borrelia resistance gene in wild rodents

Spatial variation in pathogen-mediated selection is predicted to influence the evolutionary trajectory of host populations and lead to spatial variation in their immunogenetic composition. However, to date few studies have been able to directly link small-scale spatial variation in infection risk to host immune gene evolution in natural, non-human populations. Here we use a natural rodent-Borrelia system to test for associations between landscape-level spatial variation in Borrelia infection risk along replicated elevational gradients in the Swiss Alps and Toll-like receptor 2 (TLR2) evolution, a candidate gene for Borrelia resistance, across bank vole (Myodes glareolus) populations. We found that Borrelia infection risk (i.e. the product of Borrelia prevalence in questing ticks and the average tick load of voles at a sampling site) was spatially variable and significantly negatively associated with elevation. Across sampling sites, Borrelia prevalence in bank voles was significantly positively associated with Borrelia infection risk along the elevational clines. We observed a significant association between naturally occurring TLR2 polymorphisms in hosts and their Borrelia infection status. The TLR2 variant associated with a reduced likelihood of Borrelia infection was most common in rodent populations at lower elevations that face a high Borrelia infection risk, and its frequency changed in accordance with the change in Borrelia infection risk along the elevational clines. These results suggest that small-scale spatial variation in parasite-mediated selection affects the immunogenetic composition of natural host populations, providing a striking example that the microbial environment shapes the evolution of the host’s immune system in the wild.

病原体介导选择的空间变异被预测可影响宿主种群的演化轨迹，并导致其免疫遗传组成出现空间异质性。然而迄今为止，鲜有研究能够直接将自然非人类种群中感染风险的小尺度空间变异，与宿主免疫基因的演化建立直接关联。本研究依托啮齿动物-疏螺旋体（Borrelia）自然系统，在瑞士阿尔卑斯山区的重复海拔梯度样线上，测试疏螺旋体感染风险的景观尺度空间变异与堤岸田鼠（Myodes glareolus）种群中，作为疏螺旋体抗性候选基因的Toll样受体2（TLR2）演化之间的关联。我们发现，疏螺旋体感染风险（即游离蜱的疏螺旋体感染率与采样位点处田鼠平均蜱负荷的乘积）存在空间变异，且与海拔呈显著负相关。在各采样位点中，沿海拔梯度的疏螺旋体感染风险与堤岸田鼠体内的疏螺旋体感染率呈显著正相关。我们观察到宿主天然存在的TLR2多态性与其疏螺旋体感染状态之间存在显著关联。与降低疏螺旋体感染概率相关的TLR2变异体，在面临高感染风险的低海拔啮齿动物种群中最为常见，且其频率沿海拔梯度随疏螺旋体感染风险的变化而发生改变。上述结果表明，寄生虫介导选择的小尺度空间变异会影响自然宿主种群的免疫遗传组成，为野生环境中微生物环境塑造宿主免疫系统演化提供了鲜明例证。