Complex Recombination Patterns Arising during Geminivirus Coinfections Preserve and Demarcate Biologically Important Intra-Genome Interaction Networks

Abstract

Genetic recombination is an important process during the evolution of many virus species and occurs particularly frequently amongst begomoviruses in the single stranded DNA virus family, Geminiviridae. As in many other recombining viruses it is apparent that non-random recombination breakpoint distributions observable within begomovirus genomes sampled from nature are the product of variations both in basal recombination rates across genomes and in the over-all viability of different recombinant genomes. Whereas factors influencing basal recombination rates might include local degrees of sequence similarity between recombining genomes, nucleic acid secondary structures and genomic sensitivity to nuclease attack or breakage, the viability of recombinant genomes could be influenced by the degree to which their co-evolved protein-protein and protein-nucleotide and nucleotide-nucleotide interactions are disreputable by recombination. Here we investigate patterns of recombination that occur over 120 day long experimental infections of tomato plants with the begomoviruses Tomato yellow leaf curl virus and Tomato leaf curl Comoros virus. We show that patterns of sequence exchange between these viruses can be extraordinarily complex and present clear evidence that factors such as local degrees of sequence similarity but not genomic secondary structure strongly influence where recombination breakpoints occur. It is also apparent from our experiment that over-all patterns of recombination are strongly influenced by selection against individual recombinants displaying disrupted intra-genomic interactions such as those required for proper protein and nucleic acid folding. Crucially, we find that selection favoring the preservation of co-evolved longer-range protein-protein and protein DNA interactions is so strong that its imprint can even be used to identify the exact sequence tracts involved in these interactions.

Extensive Recombination-Induced Disruption of Genetic Interactions Is Highly Deleterious but Can Be Partially Reversed by Small Numbers of Secondary Recombination Events

“…In addition, recombination breakpoint distributions found in both field-isolated geminiviruses and geminiviruses arising during recombination experiments display well-defined hot and cold spots (26,45,46,(48)(49)(50) that can strongly influence the efficiency of adaptive evolution via recombination (27). Here, however, we observed little evidence of recombination occurring at known recombination hot spots in the MSV genome and, in fact, found a number of breakpoints falling within known recombination cold spots (Fig.…”

“…Previous studies involving both natural and laboratory-derived geminiviruses that are related to MSV indicated that recombination breakpoints tend to cluster within noncoding regions of the genome. This pattern is probably due to both the mechanistic predisposition for recombination breakpoints in geminiviruses to occur at replication origins and selective forces disfavoring the survival of recombinants encoding chimeric proteins (18,(45)(46)(47)(48)(49). To the right of the phylogenetic tree is a linearized genome schematic showing the pattern of recombination and the number of breakpoints in each group of recombinant MSVs, where genomic regions in blue are derived from sMSV1 and regions in brown are derived from sMSV2.…”

Synonymous site variation due to recombination explains higher genetic variability in begomovirus populations infecting non-cultivated hosts

“…These portions were exchanged as blocks that preserve them as originating from the same genetic background. This could increase the frequency in which viable recombinants for the Rep sequence are maintained by preserving the interaction between the catalytic domains (in the Rep N-terminal portion) and their cognate iterative elements located in the 59 portion of the common region (Martin et al, 2011). Although a reduced number of breakpoints occur within the CP-encoding sequence, most of them are located in the central portion of the gene (Lefeuvre et al, 2007b).…”

SnRK1 Phosphorylation of AL2 Delays Cabbage Leaf Curl Virus Infection in Arabidopsis

“…Geminiviruses typically carry genes that encode 5 to 7 proteins that interact with a wide array of host proteins to reprogram plant cell cycle and transcriptional controls, interfere with cell signaling and protein turnover, and suppress defense pathways. Geminiviruses also display high mutation and recombination rates that allow them to adapt rapidly to new environments and new hosts (6,7). This rapid adaptation in combination with a long evolutionary history with their plant hosts has provided many opportunities for geminiviruses to modulate interactions with their hosts and enhance their success as pathogens (8).…”