An Interesting Saga of Simple
Mycobacterial Genomes
Sequence
Repeats in
Hampapathalu A. Nagarajaram
Laboratory of Computational Biology, Centre for DNA Fingerprinting and Diagnostics,
ECIL Road, Nacharam, Hyderabad-500076, Andhra Pradesh, India.
Simple sequence repeats (SSRs) or microsatellites are the repetitive nucleotide sequences
of motifs of length 1-6bp. They are scattered throughout the genomes of all the known
organisms ranging from viruses to eukaryotes. Microsatellites undergo mutations in the
form of insertions and deletions (INDELS) of their repeat units with some bias towards
insertions that lead to microsatellite tract expansion. Although prokaryotic genomes
derive some plasticity due to microsatellite mutations they have inbuilt mechanisms to
arrest undue expansions of microsatellites and one such mechanism is constituted by
post-replicative DNA repair enzymes MutL, MutH and MutS. The mycobacterial
genomes lack these enzymes and as a null hypothesis one would expect these genomes to
harbor many long tracts. However, our studies revealed severe scarcity for long tracts.
Furthermore, systematic comparison of all the equivalent microsatellites in the coding
regions revealed the presence of many polymorphic microsatellites. The coding regions
affected by frame-shifts due to microsatellite repeat unit indels, have undergone some
changes indicative of gene fission/fusion, premature termination and length variation.
Interestingly, the genes affected by frame-shift mutations code for membrane proteins,
transporters, PPE, PE_PGRS, cell-wall synthesis proteins and hypothetical proteins. This
suggests that microsatellite polymorphism plays an important role in conferring
variations in surface antigens, virulence, host-pathogen interactions and perhaps even
adaptations of the pathogens.