The specific determinants of viral fitness (or in vivo replicative capacity) are complex and poorly understood at present. The fixation of a recombinant gene within a population is likely to depend on the interplay of multiple factors. Although combining cell culture functionality data with recombination rate heterogeneity is an oversimplified view of this process, the pattern of recombination predicted by our empirical model matches remarkably well the breakpoint distributions observed in nature ( Figure 5B ). The only major deviation from this was constituted by the fourth recombination hot region observed in cell culture, which was absent from the natural breakpoint distribution ( Figures 2B and 5B ). Determining the reasons for this discrepancy will improve our understanding of the mechanisms governing the success of recombinants in nature.