Abstract
Comparison of the pattern of synonymous nucleotide substitution between two complete genomes of Mycobacterium tuberculosis at 3,298 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 35,000 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.
Highlights
We addressed the question of polymorphism in M. tuberculosis by comparing protein-coding genes in two completely sequenced genotypes, H37Rv and CDC1551 [4]
The comparison of protein-coding genes between the two M. tuberculosis genomes suggested the existence of two distinct groups of gene pairs: a large group having few or no synonymous differences and a much smaller group with a substantial degree of synonymous divergence
A number of additional possibilities may explain the occurrence of gene pairs with higher than expected per synonymous site (pS) values: 1) Balanced polymorphism
Summary
Comparison of the pattern of synonymous nucleotide substitution between two complete genomes of Mycobacterium tuberculosis at 3,298 putatively orthologous loci showed a mean percent difference per synonymous site of 0.000328 ± 0.000022. 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 35,000 ago, which is twice as high as some recent estimates of the time of origin of this species. We addressed the question of polymorphism in M. tuberculosis by comparing protein-coding genes in two completely sequenced genotypes, H37Rv and CDC1551 [4]
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