The evolutionary value of recombination is constrained by genome modularity

Abstract

Genetic recombination is a fundamental evolutionary mechanism promoting biological adaptation. Using engineered recombinants of the small single-stranded DNA plant virus, Maize streak virus (MSV), we experimentally demonstrate that fragments of genetic material only function optimally if they reside within genomes similar to those in which they evolved. The degree of similarity necessary for optimal functionality is correlated with the complexity of intragenomic interaction networks within which genome fragments must function. There is a striking correlation between our experimental results and the types of MSV recombinants that are detectable in nature, indicating that obligatory maintenance of intragenome interaction networks strongly constrains the evolutionary value of recombination for this virus and probably for genomes in general.

Figure 1. Laboratory Constructed MSV Recombinants and Their Relative Fitness (as Measured by ICLAs) in Maize

Five genome regions corresponding to the three MSV genes (MP, CP, and Rep) and two intergenic regions (LIR and SIR) were reciprocally exchanged between four pairs of MSV isolates (MSV-Mat/MSV-Kom, MSV-Mat/MSV-R2, MSV-Mat/MSV-VW, and MSV-Kom/MSV-Set). Genome-wide sequence identities are indicated. SD, standard deviation.

Figure 2. Tolerance of Recombination in MSV Differs According to the Genome Region Involved and the Degree of Divergence between Exchanged Sequences

Each plotted point represents a Ti value calculated as the average fitness of a pair of recombinant viruses with reciprocally exchanged MP genes (cyan circles), CP genes (orange diamonds), Rep genes (blue inverted triangles), SIR (red triangles), or LIR (green squares) divided by the average fitness of their parental viruses. Error bars represent the standard deviations of Ti values. Curved lines represent quadratic regressions of Ti values against parental SIR, MP, LIR, CP, and Rep nucleotide sequences.

Figure 3. The Network of Known Protein–Protein and Protein–DNA Interactions during a MSV Infection of Maize

Rep/RepA indicates the two alternative expression products of the replication-associated protein gene. Solid lines represent specific protein–protein interactions [,–18,21,22], dotted lines represent specific protein–DNA interactions [,,–21], and dashed lines indicate CP-DNA interactions of unknown specificity [–20,22]. For protein–DNA interactions, arrows point from the protein component to the DNA component of the interactions. Rep interacts with the LIR at three distinct sites [14]. CP and Rep form oligomers (solid circular arrows) [14,22]. Although CP must interact with the rest of the genome (including its own gene) during encapsidation, the sequence specificity of these interactions is unknown.

Figure 4. The Experimentally Determined Relative Recombination Tolerance of Five MSV Genomic Regions Is Highly Correlated with Values Inferred from Nature

We used the quadratic regressions presented in Figure 2 to derive experimental estimates of similarly tolerable degrees of RID in the five genomic regions over a range of Ti values between 0.99 and 0.70 (290 values at 0.01 intervals). Using a range of Ti values avoids any biases that might occur due to inadvertently choosing particularly poor/favourable Ti values for estimating similarly tolerable degrees of RID from the experimental data. For example, the set of similarly tolerable degrees of RID calculated when Ti = 0.9 is 15.3%, 8.3%, 2.7%, 3.3%, and 3.8% for the SIR, MP gene, CP gene, LIR, and Rep gene, respectively. Each of the 290 sets of values thus determined was linearly regressed against the set of values for the maximum tolerable RID inferred for the same five regions from an examination of natural recombinants (15.0%, 7.7%, 3.2%, 5.4%, and 3.9%, for SIR, MP, CP, LIR, and Rep, respectively). R ² values determined for these 290 regressions are plotted against their corresponding Ti values (solid line). The correlation is significant (broken line = R ² value corresponding to a p-value < 0.01) over the Ti range 0.95–0.7 (Pearson's R ² > 0.96, p < 0.01; Spearman's rho = 0.9, p = 0.037).