Polygenic plague resistance in the great gerbil uncovered by population
sequencing
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.