PT  - JOURNAL ARTICLE
AU  - Flemming Damgaard Nielsen
AU  - Jakob Møller-Jensen
AU  - Mikkel Girke Jørgensen
TI  - Adding context to the pneumococcal core genes – a bioinformatic analysis of the intergenic pangenome of <em>Streptococcus pneumoniae</em>
AID  - 10.1101/2021.08.29.458057
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.08.29.458057
4099  - http://biorxiv.org/content/early/2021/08/30/2021.08.29.458057.short
4100  - http://biorxiv.org/content/early/2021/08/30/2021.08.29.458057.full
AB  - Whole genome sequencing offers great opportunities for linking genotypes to phenotypes aiding in our understanding of human disease and bacterial pathogenicity. However, these analyses often overlook non-coding intergenic regions (IGRs). By disregarding the IGRs, crucial information is lost, as genes have little biological function without expression. In this study, we present the first complete pangenome of the important human pathogen Streptococcus pneumoniae (pneumococcus), spanning both the genes and IGRs. We show that the pneumococcus species retains a small core genome of IGRs that are present across all isolates. Gene expression is highly dependent on these core IGRs, and often several copies of these core IGRs are found across each genome. Core genes and core IGRs show a clear linkage as 81% of core genes are associated with core IGRs. Additionally, we identify a single IGR within the core genome that is always occupied by one of two highly distinct sequences, scattered across the phylogenetic tree. Their distribution indicates that this IGR is transferred between isolates through horizontal regulatory transfer independent of the flanking genes and that each type likely serves different regulatory roles depending on their genetic context.Competing Interest StatementThe authors have declared no competing interest.