Gene copy number variations at the within-host population level modulate gene expression in a multipartite virus

Abstract

Multipartite viruses have a segmented genome, with each segment encapsidated separately. In all multipartite virus species for which the question has been addressed, the distinct segments reproducibly accumulate at a specific and host-dependent relative frequency, defined as the ‘genome formula’. Here, we test the hypothesis that the multipartite genome organization facilitates the regulation of gene expression via changes of the genome formula, and thus via gene copy number variations. In a first experiment, the faba bean necrotic stunt virus (FBNSV), whose genome is composed of eight DNA segments each encoding a single gene, was inoculated into faba bean or alfalfa host plants, and the relative concentrations of the DNA segments and their corresponding mRNAs were monitored. In each of the two host species, our analysis consistently showed that the genome formula variations modulate gene expression, the concentration of each genome segment linearly and positively correlating to that of its cognate mRNA but not of the others. In a second experiment, twenty parallel FBNSV lines were transferred from faba bean to alfalfa plants. Upon host switching, the transcription rate of some genome segments changes but the genome formula is modified in a way that compensates for these changes and maintains a similar ratio between the various viral mRNAs. Interestingly, a deep-sequencing analysis of these twenty FBNSV lineages demonstrated that the host-related genome formula shift operates independently of DNA-segment sequence mutation. Together, our results indicate that nanoviruses are plastic genetic systems, able to transiently adjust gene expression at the population level in changing environment, by modulating the copy number but not the sequence of each of their genes.

Temporal Dynamic of the Ratio between Monopartite Begomoviruses and Their Associated Betasatellites in Plants, and Its Modulation by the Viral Gene βC1

“…For these multipartite viruses, during virus infection, a set-point of relative frequency of viral genomic components (referred to as genome formula) was found [28,29]. Additionally, changes in the relative frequency of viral genomic components were shown to contribute to the regulation of expression of genes encoded by the viral genomic components [26,27,30]. Here, we found that the betasatellite/begomovirus ratio in plants tended to become constant as infection progressed.…”

Cheating leads to the evolution of multipartite viruses

“…Alternatively, the evolution of multipartitism could open the door to further adaptations that may not have been possible for the monopartite ancestor. Many existing hypotheses for multipartitism fall into this category, such as models that assume that multipartite viruses can dynamically adjust their gene dosage to adapt to new host types, and experimental studies that show an advantage to changes in the ratios of genome segments [ 11 , 43 ]. We found that a similar kind of evolved benefit emerged in our models: when multipartitism evolves, full cheats, which encode no genes at all, are less able to exploit the resulting viral population.…”

Comprehensive Analysis of Copy Number Variations on Glycoside Hydrolase 45 Genes among Different Bursaphelenchus xylophilus Strains

“…It can be explained by the gene-dosage effect which was tagged by the associated CNV as reported in another relevant study [ 27 ]. For instance, some of the virus can adjust gene expression to deal with changing environments by modulating the copy number [ 28 ].…”