Comparative pangenomics: analysis of 12 microbial pathogen pangenomes reveals conserved global structures of genetic and functional diversity

Abstract

Background With the exponential growth of publicly available genome sequences, pangenome analyses have provided increasingly complete pictures of genetic diversity for many microbial species. However, relatively few studies have scaled beyond single pangenomes to compare global genetic diversity both within and across different species. We present here several methods for “comparative pangenomics” that can be used to contextualize multi-pangenome scale genetic diversity with gene function for multiple species at multiple resolutions: pangenome shape, genes, sequence variants, and positions within variants. Results Applied to 12,676 genomes across 12 microbial pathogenic species, we observed several shared resolution-specific patterns of genetic diversity: First, pangenome openness is associated with species’ phylogenetic placement. Second, relationships between gene function and frequency are conserved across species, with core genomes enriched for metabolic and ribosomal genes and accessory genomes for trafficking, secretion, and defense-associated genes. Third, genes in core genomes with the highest sequence diversity are functionally diverse. Finally, certain protein domains are consistently mutation enriched across multiple species, especially among aminoacyl-tRNA synthetases where the extent of a domain’s mutation enrichment is strongly function-dependent. Conclusions These results illustrate the value of each resolution at uncovering distinct aspects in the relationship between genetic and functional diversity across multiple species. With the continued growth of the number of sequenced genomes, these methods will reveal additional universal patterns of genetic diversity at the pangenome scale.

TheEscherichia coliFur pan-regulon has few conserved but many unique regulatory targets

“…Based on the data set generated, we define a pan-regulon consisting of 469 target genes that includes a union of all target genes of Fur in all nine E. coli strains studied. In analogy to pangenomic studies ( 61 , 62 ), we then divided the pan-regulon into the core regulon (the Fur regulated genes found in all the strains, n = 36), the accessory regulon (for regulated genes found in two to eight strains, n = 158), and the unique regulon (Fur regulated genes found in one strain, n = 275).…”

Alleleomes characterize the survivors of 3.5 billion years of bacterial evolution

“…The large number of available sequenced bacterial genomes [2][3][4][5] has enabled big data analysis of the sequence variants of genes, and led to the de nition of the alleleome 7 . In contrast, pan-genome analyses are based on presence/absence calls for individual genes in a set of genomes for strains of a species [32][33][34][35][36][37][38] . Thus, the alleleome is a ne-grained version of the pangenome and illuminates new information about sequence variation and selection.…”

Comparative genomic analysis of Stenotrophomonas maltophilia unravels their genetic variations and versatility trait

“…Gnuplot-4.6.6 was used to plot the characteristic curves of pangenome and obtain core genome of S. maltophilia. The functional relationship of the tted curve of the pan-genome was in terms of equation of "Heaps" law described as n=k × N -α (Hyun et al 2022).…”