Genome variation in Mycobacterium tuberculosis
Genome variation is the main underlying reason for phenotypic differences observed between organisms from the same species. This includes minor variations like single nucleotide polymorphisms, but also large sequence polymorphisms due to deletions and insertions. Some of these variations are of insignificant functional importance, but others may lead to an increase in viability and, in the case of microbes, possibly an increase in pathogenicity. However, the influence of variations on phenotype is not always dependent on the size of the mutated domain, and even single nucleotide polymorphisms can cause significant changes in an organism. This is of course an important area of research into studying pathogenic organisms and their epidemiological features. Mycobacterium tuberculosis strains also display a degree of strain variation, which has been previously suggested to be important for the outcome of disease. Certain strains are postulated to be more or less virulent, persistent, transmissible, or immunopathological. These variations do not only have important implications for the spread of the disease, but provide us with tools to characterize transmission, which have been used extensively for a number of years in tuberculosis molecular epidemiology. In this article, we discuss the different methods which are available for detecting genome variation; we look at the different mechanisms which cause this variation (including insertions, deletions, duplications and single nucleotide polymorphisms), and review the consequences and implications of this genome variation with regard to Mycobacterium tuberculosis pathogenicity.