Linking pangenomes and metagenomes: the Prochlorococcus metapangenome

Pangenomes offer detailed characterizations of core and accessory genes found in 'a set of closely related microbial genomes, generally by clustering genes based on sequence homology. In comparison, metagenomes facilitate highly resolved investigations of the relative distribution of microbial genomes and individual genes across environments through read recruitment analyses. Combining these complementary approaches can yield unique insights into the functional basis of microbial niche partitioning and fitness, however, advanced software solutions are lacking. Here we present an integrated analysis arid visualization strategy that provides an interactive arid reproducible frame work to generate pangenomes arid to study them in conjunction with metagenomes. To investigate its utility, we applied this strategy to a Prochlorococcus pangenorne in the context of a large-scale marine rnetagenornic survey. The resulting Prochlorococcus metapangenome revealed remarkable differential abundance patterns between very closely related isolates that belonged to the same phylogenetic cluster and that differed by only a small number of gene clusters in the pangenome. While the relationships between these genornes based on gene clusters correlated with their environmental distribution patterns, pylogenetic analyses using marker genes or concatenated single-copy core genes did not recapitulate these patterns. The metapangenome also revealed a small set of core genes that mostly occurred in hypervariable genornic islands of the Prochlorococcus populations, which systematically lacked read recruitment from surface ocean metagenomes. Notably, these core gene clusters were all linked to sugar metabolism, suggesting potential benefits to Prochlorococcus from a high sequence diversity of sugar metabolism genes. The rapidly growing number of microbial genomes and increasing availability of environmental rnetagenomes provide new opportunities to investigate the functioning and the ecology of microbial populations, and metapangenomes can provide unique insights for any taxon and biome for which genomic and sufficiently deep metagenomic data are available.