![]() ![]() Much less clear is how interference affects the evolution of molecular phenotypes, such as protein stabilities and affinities governing gene regulation and cellular metabolism. The resulting fitness cost of interference, which has also been been observed in microbial laboratory evolution 20, 21, 22, 23, is the center piece of classic arguments for the evolutionary advantage of sex 24, 25, 26, 27, 28. Second, interference reduces the speed of evolution 7, 8, 9, 11, 12, 13 this has been observed in laboratory evolution experiments 16, 17, 18, 19. First, interference selection rather than genetic drift constrains the genetic diversity in large populations, which, in turn, limits the efficacy of selection 10, 13, 14, 15. Recent theory 5, 6, 7, 8, 9, 10, 11, 12, 13 has quantified two broad interference effects in asexual evolution. These interactions and their consequences for genome evolution have been studied extensively in laboratory experiments 1, 2 and in natural populations 3, 4. Interference interactions between loci include background selection (the spread of a beneficial allele is impeded by linked deleterious alleles), hitchhiking or genetic draft (a neutral or deleterious allele is driven to fixation by a linked beneficial allele), and clonal interference between beneficial alleles originating in disjoint genetic clades (only one of which can reach fixation). That is, selection on an allele at one genomic locus can interfere with the evolution of simultaneously present alleles throughout the genome. ![]() In the absence of recombination, evolution is constrained by genetic linkage. In a broader context, our analysis suggests that the systems biology of microbes is strongly intertwined with their mode of evolution. Recombination above a threshold rate can eliminate this cost, which establishes a universal, biophysically grounded scenario for the evolution of sex. Biological implications of phenotypic interference include rapid collateral system degradation in adaptation experiments and long-term selection against genome complexity: each additional gene carries a cost proportional to the total number of genes. We find a generic mode of phenotypic interference that couples the function of individual genes and the population’s global evolutionary dynamics. Our analysis uses biophysically grounded evolutionary models for molecular phenotypes, such as fold stability and enzymatic activity of genes. ![]() Here we show how interference impacts systems biology by constraining genetic and phenotypic complexity. ![]() The evolution of microbial and viral organisms often generates clonal interference, a mode of competition between genetic clades within a population. ![]()
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