Old origin of a protective endogenous retrovirus (enJSRV) in the Ovis genus

Abstract

Sheep, the Jaagsiekte sheep retrovirus (JSRV) and its endogenous forms (enJSRVs) are a good model to study long-time relationships between retroviruses and their hosts. Taking advantage of 76 whole genome resequencing data of wild and domestic Ovis, we investigated the evolution of this relationship. An innovative analysis of re-sequencing data allowed characterizing 462 enJSRVs insertion sites (including 435 newly described insertions) in the Ovis genus. We focused our study on endogenous copies inserted in the q13 locus of chromosome 6 (6q13). Those copies are known to confer resistance against exogenous JSRV thanks to alleles bearing a mutation in the gag gene. We characterized (i) the distribution of protective and non-protective alleles across Ovis species and (ii) the copy number variation of the 6q13 locus. Our results challenged the previous hypothesis of fixation and amplification of the protective copies in relation with domestication, and allowed building a new model for the evolution of the 6q13 locus. JSRV would have integrated the 6q13 locus after the Ovis-Capra divergence (5-11 MYA) and before the Ovis diversification (2.4-5 MYA). The protective mutation in the enJSRV 6q13 copy appeared shortly after its insertion and was followed by genomic amplifications, after the divergence between Pachyform lineage on one side and the Argaliform and moufloniform lineages on the other (2.4-5 MYA). Considering the potential selective advantage of the protective mutation, its fixation in both sheep and its closest wild relative Ovis orientalis may be due to natural selection before domestication from O. orientalis populations.

Fig. 1

enJSRV presence (blue) absence (grey) heatmap. Individuals (lines) are ordered in species (Oa Ovis aries, Oo Ovis orientalis, Ov Ovis vignei, Oc Ovis canadensis, Od Ovis dalli) and enJSRV (columns) are ordered based on their relative binary distance. Only enJSRVs present in at least two individuals were kept. Layered barplot represent quantile 95 of coverage in insertion window. Red arrow indicates 6q13 insertion site

Fig. 2

Pairwise comparison of the number enJSRV-6q13, the total number of enJSRV in the genome and the number of R/W mutations. Relationship between the number of enJSRV in 6q13 region and the number of enJSRV R/W mutants in the genome (a), between the number of enJSRV in 6q13 region and the number of enJSRV in the genome (b) and between the number of enJSRV in the genome and the proportion of R/W sequences in the genome (c)