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Polygenic plague resistance in the great gerbil uncovered by population sequencing
  • +14
  • Pernille Nilsson,
  • Mark Ravinet,
  • Yujun Cui,
  • Paul Berg,
  • Yujiang Zhang,
  • Rong Guo,
  • Tao Luo,
  • Yajun Song,
  • Emiliano Trucchi,
  • Siv Hoff,
  • Ruichen Lv,
  • Boris V. Schmid,
  • W. Ryan Easterday,
  • Kjetill S. Jakobsen,
  • Niels Christian Stenseth,
  • Ruifu Yang,
  • Sissel Jentoft
Pernille Nilsson
University of Oslo

Corresponding Author:[email protected]

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Mark Ravinet
University of Nottingham
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Yujun Cui
State Key Laboratory of Pathogen and Biosecurity
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Paul Berg
University of Oslo
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Yujiang Zhang
Xinjiang Uighur Autonomous Region Center for Disease Control and Prevention
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Rong Guo
Xinjiang Uighur Autonomous Region Center for Disease Control and Prevention
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Tao Luo
Xinjiang Uighur Autonomous Region Center for Disease Control and Prevention
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Yajun Song
State Key Laboratory of Pathogen and Biosecurity
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Emiliano Trucchi
Department of Life and Environmental Sciences, Marche Polytechnic University, Via Brecce Bianche, 60131
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Siv Hoff
University of Oslo
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Ruichen Lv
State Key Laboratory of Pathogen and Biosecurity
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Boris V. Schmid
University of Oslo
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W. Ryan Easterday
University of Oslo
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Kjetill S. Jakobsen
University of Oslo
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Niels Christian Stenseth
University of Oslo
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Ruifu Yang
State Key Laboratory of Pathogen and Biosecurity
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Sissel Jentoft
University of Oslo
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Abstract

Pathogens may elicit a high selective pressure on hosts and can alter genetic diversity over short evolutionary timescales. Intraspecific variation in immune response can be observed as variable survivability from specific infections. The great gerbil (Rhombomys opimus) is a rodent plague host with a heterogenic but highly resistant phenotype. Here, we investigate if the most plague-resistant phenotypes are linked to genomic differences between survivors and susceptible individuals by exposure of wild-caught great gerbils from Northwest China to plague (Yersinia pestis). Whole genome sequencing of ten survivors and ten moribund individuals revealed a low genome-wide mean divergence, except for a subset of genomic regions that showed elevated differentiation. Gene ontology (GO) analysis of candidate genes within regions of increased differentiation, demonstrated enrichment of pathways involved in transcription and translation and their regulation), as well as genes directly involved in immune functions, cellular metabolism and the regulation of apoptosis. Differential RNA expression 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.
01 Nov 2022Published in PNAS Nexus volume 1 issue 5. 10.1093/pnasnexus/pgac211