Selection-based model of prokaryote pangenomes

Abstract The genomes of different individuals of the same prokaryote species can vary widely in gene content, displaying different proportions of core genes, which are present in all genomes, and accessory genes, whose presence varies between genomes. Together, these core and accessory genes make up a species’ pangenome. The reasons behind this extensive diversity in gene content remain elusive, and there is an ongoing debate about the contribution of accessory genes to fitness, that is, whether their presence is on average advantageous, neutral, or deleterious. In order to explore this issue, we developed a mathematical model to simulate the gene content of prokaryote genomes and pangenomes. Our model focuses on testing how the fitness effects of genes and their rates of gene gain and loss would affect the properties of pangenomes. We first show that pangenomes with large numbers of low-frequency genes can arise due to the gain and loss of neutral and nearly neutral genes in a population. However, pangenomes with large numbers of highly beneficial, low-frequency genes can arise as a consequence of genotype-by-environment interactions when multiple niches are available to a species. Finally, pangenomes can arise, irrespective of the fitness effect of the gained and lost genes, as long as gene gain and loss rates are high. We argue that in order to understand the contribution of different mechanisms to pangenome diversity, it is crucial to have empirical information on population structure, gene-by-environment interactions, the distributions of fitness effects and rates of gene gain and loss in different prokaryote groups.