Fig. 1

DNA fragment inversion concomitantly inverts GC skew values. a The effect of DNA fragment inversion on GC Skew. An example DNA sequence oriented with the leading strand on top and its post-inversion form are depicted. The box indicates that the upper strand is used for GC skew calculation by convention. The GC skew calculation shows that the relative abundance of guanine and cytosine residues in the top strand are reversed upon DNA inversion, resulting in an inverse GC skew value. b GC skew values along the top strand are plotted on the M. tuberculosis H37Rv genome. GC skew values switch from positive (green) to negative (purple) at ori/ter regions due to opposing replication fork orientations. Inversions are apparent as deviations from strand averages (two examples are indicated by gray arrows). c Anecdotal examples of four genes that naturally inverted in specific Mtb strains as identified by closed genome analysis. The ancestral orientation of each allele is indicated above the corresponding column (HO or CD) as inferred from the positive GC skew value. Columns are marked with GC skew values. Gene names are indicated under each column. Inverted alleles (always with both opposing orientations and GC skew values) were found in the following strains: Gene Rv1377c: Strain KIT87190, Gene Rv3092c: Strain F1, Genes emrB and purC: Strain 37004