Nilsson Pernille, Ravinet Mark, Cui Yujun, Berg Paul R, Zhang Yujiang, Guo Rong, Luo Tao, Song Yajun, Trucchi Emiliano, Hoff Siv N K, Lv Ruichen, Schmid Boris V, Easterday W Ryan, Jakobsen Kjetill S, Stenseth Nils Chr, Yang Ruifu, Jentoft Sissel
Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, 0371 Oslo, Norway.
School of Life Sciences, University of Nottingham, NG9 8DQ, UK.
PNAS Nexus. 2022 Oct 5;1(5):pgac211. doi: 10.1093/pnasnexus/pgac211. eCollection 2022 Nov.
Pathogens can elicit high selective pressure on hosts, potentially altering genetic diversity over short evolutionary timescales. Intraspecific variation in immune response is observable as variable survivability from specific infections. The great gerbil () is a rodent plague host with a heterogenic but highly resistant phenotype. Here, we investigate the genomic basis for plague-resistant phenotypes by exposing wild-caught great gerbils to plague (). Whole genome sequencing of 10 survivors and 10 moribund individuals revealed a subset of genomic regions showing elevated differentiation. Gene ontology analysis of candidate genes in these regions demonstrated enrichment of genes directly involved in immune functions, cellular metabolism and the regulation of apoptosis as well as pathways involved in transcription, translation, and gene regulation. Transcriptomic analysis revealed that the early activated great gerbil immune response to plague consisted of classical components of the innate immune system. Our approach combining challenge experiments with transcriptomics and population level sequencing, provides new insight into the genetic background of plague-resistance and confirms its complex nature, most likely involving multiple genes and pathways of both the immune system and regulation of basic cellular functions.
病原体可对宿主施加高度的选择压力，有可能在较短的进化时间尺度上改变遗传多样性。免疫反应的种内变异表现为特定感染后的可变生存能力。大沙鼠是一种啮齿动物鼠疫宿主，具有异质性但高度抗性的表型。在此，我们通过将野生捕获的大沙鼠暴露于鼠疫杆菌来研究抗鼠疫表型的基因组基础。对10只存活个体和10只濒死个体进行全基因组测序，发现了一部分分化程度升高的基因组区域。对这些区域中的候选基因进行基因本体分析，结果表明直接参与免疫功能、细胞代谢和细胞凋亡调控的基因以及参与转录、翻译和基因调控的途径显著富集。转录组分析显示，大沙鼠对鼠疫的早期激活免疫反应由固有免疫系统的经典成分组成。我们将攻毒实验与转录组学和群体水平测序相结合的方法，为抗鼠疫的遗传背景提供了新的见解，并证实了其复杂性，很可能涉及免疫系统和基本细胞功能调控的多个基因和途径。
