Evolutionary dynamics of cytoplasmic segregation and fusion : Mitochondrial 1 mixing facilitated the evolution of sex at the origin of eukaryotes

8 Sexual reproduction is a trait shared by all complex life, but the complete account of its origin 9 is missing. Virtually all theoretical work on the evolution of sex has been centered around the 10 benefits of reciprocal recombination among nuclear genes, paying little attention to the 11 evolutionary dynamics of the multi-copy mitochondrial genome. Here we develop a 12 mathematical model to study the evolution of nuclear alleles inducing cell fusion in an 13 ancestral population of clonal proto-eukaryotes. Segregational drift maintains high 14 mitochondrial variance between clonally reproducing hosts, but the effect of segregation is 15 opposed by cytoplasmic mixing which tends to reduce variation between cells in favor of 16 higher heterogeneity within the cell. Despite the reduced long-term population fitness, alleles 17 responsible for sexual cell fusion can spread to fixation. The evolution of sex requires 18 negative epistatic interactions between mitochondrial mutations and is promoted by strong 19 purifying selection, low mutant load and weak mitochondrial-nuclear associations. We argue 20 that similar conditions were maintained during the late stages of eukaryogenesis, facilitating 21 the evolution of sexual cell fusion and meiotic recombination without compromising the 22 stability of the emerging complex cell. 23