The genome of the plague-resistant great gerbil reveals species-specific duplication of an MHCII gene

Abstract

Background The great gerbil (Rhombomys opimus) is a social rodent living in permanent, complex burrow systems distributed throughout Central Asia, where it serves as the main host of several important vector-borne infectious diseases and is defined as a key reservoir species for plague (Yersinia pestis). Studies from the wild have shown that the great gerbil is largely resistant to plague but the genetic basis for resistance is yet to be determined. Results Here, we present a highly contiguous annotated genome assembly of great gerbil, covering over 96 % of the estimated 2.47 Gb genome. Comparative genomic analyses focusing on the immune gene repertoire, reveal shared gene losses within TLR gene families (i.e. TLR8, TLR10 and all members of TLR11-subfamily) for the Gerbillinae lineage, accompanied with signs of diversifying selection of TLR7 and TLR9. Most notably, we find a great gerbil-specific duplication of the MHCII DRB locus. In silico analyses suggest that the duplicated gene provides high peptide binding affinity for Yersiniae epitopes. Conclusion The great gerbil genome provides new insights into the genomic landscape that confers immunological resistance towards plague. The high affinity for Yersinia epitopes could be key in our understanding of the high resistance in great gerbils, putatively conferring a faster initiation of the adaptive immune response leading to survival of the infection. Our study demonstrates the power of studying zoonosis in natural hosts through the generation of a genome resource for further comparative and experimental work on plague survival and evolution of host-pathogen interactions.

A high-density genetic map and molecular sex-typing assay for gerbils

“…Gerbils have also become popular as a medical model for a variety of human diseases. The great gerbil ( Rhombomys opimus ) is a known reservoir of human pathogens including the plague (Nilsson et al 2018 ) and leishmaniasis (Ahmad 2002 ). Research on the great gerbil has spanned ecology (Linné Kausrud et al 2007 ) and immune function (Nilsson et al 2018 ) in an effort to mitigate these major human health concerns.…”

A high-density genetic map and molecular sex-typing assay for gerbils

“…Gerbils have also become popular as a medical model for a variety of human diseases. The great gerbil (Rhombomys opimus) is a known reservoir of human pathogens including the plague (Nilsson et al 2018) and leishmaniasis (Ahmad 2002).…”

“…Research on the great gerbil has spanned ecology (Linné Kausrud et al 2007) and immune function (Nilsson et al 2018) in an effort to mitigate these major human health concerns. The fat sandrat (Psammomys obsesus), being well adapted to low calorie food sources, is highly susceptible to diabetes and is thought to share a similar genetic architecture as humans (Shafrir and Ziv 2009) which makes it an ideal model system.…”

“…While a great deal of cytological research has been done on various gerbils (Cohen 1970;Benazzou et al 1982), there has been no bridge yet between the new genomics era and these classic karyotype studies. Three gerbil species (Mongolian gerbils, fat sandrats, and great gerbils) have all recently had their genomes sequenced (Hargreaves et al 2017;Zorio et al 2018;Nilsson et al 2018). But as yet, none of these genomes are complete and all assemblies are highly fragmented.…”

“…Nor has any effort been made to increase contiguity of the gerbil genomes. Indeed, the least fragmented genome is from the great gerbil and contains only 6,390 scaffolds (Nilsson et al 2018) which is impressive for shotgun sequencing, but not a chromosome-level assembly. In contrast, the fat sandrat genome has 150,763 scaffolds and the Mongolian gerbil genome has 68,793.…”