Genomewide pattern of synonymous nucleotide substitution in two complete genomes of Mycobacterium tuberculosis

Abstract

Comparison of the pattern of synonymous nucleotide substitution between two complete genomes of Mycobacterium tuberculosis at 3298 putatively orthologous loci showed a mean percent difference per synonymous site of 0.000328 0.000022. Although 80.5% of loci showed no synonymous or nonsynonymous nucleotide differences, the level of polymorphism observed at other loci was greater than suggested by previous studies of a small number of loci. This level of nucleotide difference leads to the conservative estimate that the common ancestor of these two genotypes occurred approximately 35000 ago, which is twice as high as some recent estimates of the time of origin of this species. Our results suggest that a large number of loci should be examined for an accurate assessment of the level of nucleotide diversity in natural populations of pathogenic microorganisms.

Figure

A plot of p(A|p_S), the probability of assignment of a locus to group A given the observed p_S value, as a function of p_S at 3,309 loci compared between the H37Rv and CDC1551 genotypes of Mycobacterium tuberculosis. The plot shows the bimodal nature of the distribution of p_S values, with overall higher values of p_S at the 11 loci having p(A|p_S) >50%.