Our results show that interferences between pairs of loci are negative: a recombination event between two loci apparently increases the probability of recombination between another pair of loci. We believe that the most parsimonious explanation of these negative interferences is based on the way the infection builds up within plant hosts. Indeed, one can divide infected host cells into those infected by a single virus genotype and those infected by more than one viral genotype. In the former, analogous to clonal propagation, recombination is undetectable. In the latter, recombination is not only detectable but, as our results indicate, very frequent. Samples consisting of viruses resulting from a mixture of these two types of host cell infections will thus contain viruses with no recombination and viruses with several recombination events, thus yielding an impression of negative interference. These conceptual arguments are supported by mathematical models. It is indeed easy to show (detailed results not shown) that if a proportion F of the population reproduces clonally, analogous to single infections, while the remaining reproduces panmictically, negative interferences could be inferred even if they do not exist. For example, assuming a three-locus model with real recombination rates r 1 and r 2 and interference i 12 , the ''apparent'' recombination and interference parameters, would be r 1 = (1 À F)r 1 , r 2 = (1 À F)r 2 , and i 12 = À(F À i 12 )/(1 À F). Interestingly, this example also shows that our estimates of the recombination rate are conservative: that a fraction F of host cells are singly infected while others are multiply infected leads to an underestimation of the recombination rate. As judged by r 1 , r 2 , and r 3 , calculated between markers a-b, b-c, and c-d, respectively, we found evidence for recombination through the entire CaMV genome. The values for r 1, r 2 , and r 3 are remarkably similar, hence the recombination sites seem to be evenly distributed along the genome. We considered the template-switching model as the major way recombinants are created in CaMV. As already mentioned in the Introduction, hot spots of template switching have been predicted at the position of the 59 extremities of the 35S and 19S RNAs [21, 36, 42] . If other recombination mechanisms, such as that associated with second-strand DNA synthesis or with the host cell DNA repair machinery, act significantly, hot The various parameters are as follows: r1, recombination rate between markers a and b; r2, recombination rate between markers b and c; r3, recombination rate between markers c and d; i12, interference between crossovers in segments a-b and b-c; i23, interference between crossovers in segments b-c and c-d; i13, interference between crossovers in segments a-b and c-d; i123, second-order interference accounting for residual interference. The recombination rates are the maximum likelihood estimates (6 95% confidence intervals). The interference parameters were obtained numerically as explained in the Materials and Methods. DOI: 10.1371/journal.pbio.0030089.t002 spots would be expected at the positions of the sequence interruption D1, D2, and D3 [43] . Due to the design of our experiment and the position of the four markers, we have no information on putative hot spots at positions corresponding to the 59 end of the 35S RNA and to D1 (at nucleotide position 0). Nevertheless, the putative hot spots at the 59 end of the 19S RNA and at D2 and D3 (nucleotide positions 4,220 and 1,635, respectively) fall between marker pairs c-d, b-c, and a-b, respectively. Our results indicate that either these hot spots are quantitatively equivalent-though predicted by different recombination mechanisms-or, more likely, that they simply do not exist. Whatever the explanation, what we observe is that the CaMV can exchange any portion of its genome, and thus any gene thereof, with an astonishingly high frequency during the course of a single host infection. To our knowledge, the viral recombination rate has never previously been quantified experimentally for a plant virus [3] . In contrast, retroviruses and particularly HIV-1 have been extensively investigated in that sense. As we have already discussed for these latter cases, the quantification of the intrinsic recombination rate was carried out in artificially coinfected cell cultures. The estimated intrinsic per nucleotide per generation recombination rate in HIV-1 is on the order of 10 À4 [14, 15, 19] , less than one order of magnitude higher than our estimation for CaMV. Because for various reasons detailed above we probably underestimate the within-host CaMV recombination rate, we believe that the intrinsic recombination rate in CaMV is higher and perhaps on the order of that of HIV.