Project : Simple Sequence Repeats in Bacterial Genomes: Analysis of their abundance, enrichment and polymorphism

	Simple sequence repeats (SSRs), also known as microsatellites, are the repetitive nucleotide sequences of motifs of length 1 - 6 bp which are found in every genome known so far. They are more than mere repetitive sequences. Their roles have been attributed to many biological functions. For instance, the genes responsible for virulence of many pathogenic bacteria have been shown to contain these repetitive elements. SSRs undergo mutations in the form of insertions and deletions (INDELS) of their repeat units with some bias towards insertions that lead to repeat tract expansion. Prokaryotic genomes derive some plasticity due to SSR mutations. Variations in repeat numbers in SSRs in the coding regions bring about drastic changes to their gene products, as a consequence of premature termination due to frameshift. Such changes in the coding regions have been shown to cause phase variations in pathogenic bacteria, which impart greater defensive capability to the pathogens to escape hostile host environment. SSRs also act as gene regulators where loss or gain of repeats in the promoter region can regulate transcriptional activity. In this way SSRs inculcate a considerable genome plasticity to adjust to different physical and physiological host environments. We have been studying bacterial genomes of interest for abundance, enrichment and polymorphism SSRs. As part of our studies we developed MICdb (Sreenu et al, 2002), a database of prokaryotic microsatellite and viral sequenced genomes and a web-server MICAS (Sreenu et al, 2002) to host MICdb and SSRF, webbased program to extract perfect SSRs from nucleotide sequences. We have so far analysed the known mycobacterial genomes since these genomes lack the mismatch repair enzymes mutL, mutH and mutS. As a null hypothesis one would expect these genomes to harbour long enriched SSRs. However, our studies revealed that these genomes show a severe scarcity of such SSRs (Sreenu et al 2006). Cross-genome comparisons yielded novel functional implications of SSR polymorphism (Sreenu et al 2006). We are currently analyzing known yersinia genomes and plasmodium genomes. Very recently we developed a novel tool to identification of imperfect SSRs, which is the most sensitive and fast (Mudunuri and Nagarajaram, 2007). Currently we are analyzing imperfect SSRs in genomes of interest.
	Tools Developed by us MICAS: Microsatellite Analysis Server hosting MICdb. IMEx: Imperfect Microsatellite Extractor.
People Involved Pankaj Kumar Senior Research Fellow Suresh Babu M Project Assistant V.B.Sreenu Former PhD Student
	Publications Research Articles V.B.Sreenu, Vishwanath Alevoor, J.Nagaraju and H.A.Nagarajaram 2003 MICdb: Database of Prokaryotic Microsatellites Nucleic Acids Research 31 106-108. V.B.Sreenu, G.Ranjitkumar, S.Swaminathan, S.Priya, B.Bose, M.N.Pavan, Geetha Thanu, J.Nagaraju and H.A.Nagarajaram 2003 MICAS: A fully automated web server for microsatellite extraction and analysis from prokaryote and viral genomic sequences. Applied Bioinformatics 2(3) 165-168. Sreenu, V.B., Ranjitkumar, G., Swaminathan, S., Priya, S., Bose, B., Narendra Pavan, M., Nagaraju, J., Nagarajaram, H.A. (2004) MICdb - Database of Prokaryotic Microsatellites. Nucleic Acids Research Published in online database issue Sreenu,V.B., Kumar, P., Nagaraju, J. and Nagarajaram, H.A. (2006) Microsatellite polymorphism across the M. tuberculosis and M. bovis genomes: Implications on genome evolution and plasticity. BMC Genomics 7:78-88 (Highly accessed article) Sreenu V B, Kumar P, Nagaraju J and Nagarajaram H A 2007 Simple sequence repeats in mycobacterial genomes; J. Biosci. 32 3-15 Suresh B. M. and Nagarajaram, H.A. (2007) IMEx: Imperfect Microsatellite Extractor Bioinformatics (In Press) Kumar Pankaj and H.A.Nagarajaram Distribution, Enrichment and Polymorphism of Simple Sequence Repeats in Yersinia Genomes (manuscript communicated) Suresh B. M. and Nagarajaram, H.A. IMEx-web: A web server for extraction and analysis of simple sequence repeats in whole genome sequences (manuscript communicated) Posters Presented Kumar, P and Nagarajaram, H.A. (2006): "Microsatellite Distribution, Enrichment and Polymorphism in Yersinia GenomesDynamics-Function." presented at INCOB, 2006 New Delhi. Kumar P, V.B.Sreenu and Nagarajaram, H.A. (2006): "Microsatellite Polymorphism in Prokaryotic Genomes: Implications on Pathogen Adaptation, Survival and Evolution." presented at International Symposium on NEW FRONTIERS IN TUBERCULOSIS RESEARCH, 2006 New Delhi.