Fig. 3: GalNAc utilization underlies the ABO association with F. prausnitzii SVs.
From: Host genetic regulation of human gut microbial structural variation
a, Association between ABO blood type and the presence or absence of genomic segment 577–579 kb (SV 577–579) of F. prausnitzii is dependent on FUT2 secretor status. Individuals were grouped into different groups on the basis of blood types (A versus B or O blood types) and FUT2 secretor status (secretors versus non-secretors). The y axis refers to the fraction of individuals with the 577–579-kb region in the DMP dataset. Unadjusted association P values are reported, based on linear mixed models. b, A scheme of the GalNAc pathway identified in the associated SV region, which is divided into the initial cleavage from A-antigen (step 0) and five key steps of GalNAc utilization (steps 1–5; Supplementary Note 3). agaF + V + C+ D genes encode four subunits of the GalNAc PTS system II complex protein. DHAP, dihydroxyacetone phosphate; FBP, fructose-1,6-bisphosphate; F6P, fructose 6-phosphate; GAP, glyceraldehyde 3-phosphate; PTS, phosphotransferase system; TBP, tagatose 1,6-bisphosphate. Created with BioRender.com. c, A phylogenetic tree of the strains used for the culture experiments and organization of genes involved in GalNAc utilization in the SV region. The x axis indicates the base pair position starting from the flanking gene dinB. The different coloured lines indicate the location of the same genes in different strains. The names of strains with and without the SV region are in red and black, respectively. d,e, Growth curves of F. prausnitzii strains with or without SV 577–579 on medium with GalNAc (d) and galactose (e). The x axis refers to time points in hours. The y axis refers to cell density as measured as the optical density at 600 nm (OD600nm). Points with bars on the growth curves represent means ± s.d. of three replicates. f, Fold change of gene expression following GalNAc induction compared to glucose induction. The y axis shows the fold change of the expression of the agaC, agaD, agaV and agaF genes in the strains HTF-495 and ATCC 27768 following GalNAc induction relative to glucose induction. Each dot indicates one replicate. Bars and error bars indicate means ± s.e. of three replicates.
