Hampapathalu A. Nagarajaram

Title: An Interesting Saga of Simple Sequence Repeats in Mycobacterial Genomes 

Laboratory of Computational Biology, Centre for DNA Fingerprinting and Diagnostics, ECIL Road, Nacharam, Hyderabad-500076, Andhra Pradesh, India. 

Abstract

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.

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