A Neutral Theory of Genome Evolution and the Frequency Distribution of Genes

The gene content of genomes of closely related bacteria can differ significantly. For example, pair-wise comparisons of genome sequences from isolates of the same species often do not share a substantial fraction of their gene content. When a large number of genomes within a bacterial “species ” are sequenced, the gene content variability can be summarized as a gene frequency distribution: given G sequenced genomes, some genes are found in k of these genomes where k ranges from 1 to G. Empirically, such gene frequency distributions possess a characteristic U-shape, such that there are many genes that only appear in one genome, fewer genes which appear in an intermediate number of genomes, and many genes which appear in all genomes. Genes within each of these three categories have been labeled accessory, character and core genes, respectively1. It would seem that U-shaped gene frequency distributions can be used to infer the essentiality and/or importance of a gene to a species. Instead, we ask: is it possible to recapitulate findings of U-shaped gene frequency distributions in the absence of selective forces driving genomic and population composition? Here, we answer this question in the affirmative by proposing a simple and analytically tractable neutral model of genome evolution that explicitly accounts for gene composition of genomes. In this model, genomes undergo birth-death processes in a neutral sense and also acquire and lose genes. The model differs from most previous efforts to analyze genome evolution by self-consistently treating the dynamics at two scales: population level drift and genomic level change. We analyze our model using coalescent theory and derive closed form solutions for gene frequency distributions. We find that gene frequency distributions in the model possess a characteristic U-shape even in the absence of selective forces driving genome and population structure. We fit model predictions t