Brachyspira hyodysenteriae [5], an anaerobic intestinal spirochaete that colonizes niches of swine colon and causes dysentery of pigs, a disease of significant economic importance. It appears that the bacterium may have evolved strategies to survive and adapt via gene transfer in the intestinal environment. The genome sequence data suggests presence of genes encoding an- aerobic metabolism and mechanisms to cause mucosal damage through the activ- ity of many different virulence factors facilitated by chemotaxis and motility. Interestingly, the chunks of genes believed to have been horizontally acquired by Brachyspira, and that are supposed to have facilitated adaptation and survival of the bacterium within the intestines, belonged mostly to classically ‘enteric type’ of organisms, rather than to other spirochaet- al relatives of Brachyspira [5]. Whole genome sequencing and analysis of Mycobacterium indicus pranii (MIP) togeth- er with molecular phylogenetic analyses [6] revealed a unique soil and water dwelling lifestyle for this ‘generalist’ or- ganism. MIP had a common ancestor with pathogenic Mycobacterium avium intracellulare complex that did not prefer parasitic adaptation but a free living life-style. Further analysis suggests a shared aquatic phase of MIP with the early pathogenic forms of Mycobacterium, well before the latter diverged to form ‘specialist’ bacterial parasites. This information has an impor- tant bearing on our understanding of mycobacterial evolution. Genomic downsizing and streamlining has been a dominant evolutionary trend in mycobacterial genome evolution that perhaps shapes their host-range and tissue tropism giving rise to ‘specialist’ lineages [6,7]. Another interesting exam- ple of genome optimization through reduction - based - metabolic optimiza- tion comes from Yersinia pestis which originated from its closest relative Y. pseudotuberculosis [8]. The same has been true in the case of Brucella ovis whose genome is shorter than the classical zoonotic strains [9] oving to loss of genes via pseudogenization and degradation that has happened concomitant to the narrowing of its host range; it infects only sheep [10]. It has been suggested that inactivation of genes linked to nutrient acquisition and utilization, cell envelope structure and those encoding urease may have played a role in narrowing of the tissue predilection and host range of B. ovis [10]. Another important feature of the B. ovis genome has been the presence of increased number of transposable elements thus hinting towards frequent shuffling (genomic fluidity, or plasticity) of its genome [10]. Variation in gene content, especially the flexible or unstable part of the genome such as mobile elements and genomic islands, has been shown to influence phenotypes such as virulence and antimi- crobial resistance. This is especially true for some of the biomedically significant organisms such as the Group A Streptococcus (GAS). Recently, a study analyzing twelve sequenced GAS genomes [11] determined that the resultant ‘metagenome’ holds tremendous potential for understanding pathobiology of the GAS. This multi- genome dataset provides an opportunity to address putative functions, encoded by the exogenous genetic elements, such as antimicrobial resistance. Another major benefit from these genomes includes the ability to develop molecular markers based on GAS mobile elements to tag and track field-level diversity of the circulating strains; this will be of paramount signifi- cance in vaccine development and testing. Why sequence multiple species and strains? A wide variety of microbial sequencing projects having been completed or being implemented throughout the world has created a rich and diverse ‘mega-database’ of microbial genomes. However, to fully gauge the prevailing diversity and stratifi- cation patterns of all bacterial species, it will be required to sequence hundreds and thousands of genomes representing all branches and lineages within the bacterial and archaeal part of the tree of life wherein each of the phylum provides an opportunity to capture evolutionary foot- prints of billions of years. It is estimated that there are at least 35 different phyla of bacteria according to the rRNA gene sequence based tree of life [12]. The genome sequences of bacteria that have accumulated so far represent only three phyla, thus leaving major gaps in the genomic representation of the bacterial diversity of our biosphere. It is therefore urgently required to sequence genomes from underrepresented phyla and to improve resolution of deep branches in the bacterial tree so as to enable biological studies of important lineages and to decipher novel functions thereof. In view of these facts more systematic approaches to the sequencing of the microbial ge- nomes are needed to leverage data for the interpretations of environmental surveys as well as to facilitate comparative geno- mic analyses and annotations of different genomes and microbiomes. The GEBA Prokaryotic Genomes Multiply (Genomic Encyclopedia of Bacteria and Archaea) project is one such ‘community phylogenomics’ initiative that is being implemented at the Joint Genome Insti- tute (http://www.jgi.doe.gov/programs/ GEBA/). This program aims at filling the genomic gaps pertaining to bacterial and archaeal branches of the tree of life while using the tree itself as a guide to identify which target microorganisms need to be sequenced completely. Some of the potential benefits of the GEBA project include identification of new protein families across different lineages of bacte- rial phyla so as to provide a comparative genomics and proteomics platform to- wards annotation of forthcoming genomes and microbiomes of the same or different phyla. Also, it will facilitate improved phylogenetic anchoring of metagenomic data-sets besides providing better under- standing of the processes underlying the evolutionary diversity and functional strat- ification of different microbes inhabiting various different niches in the environ- ment. Many of the pathogenic bacterial spe- cies are monomorphic meaning that they present very little diversity upon genetic fingerprinting or limited sequence profil- ing. Gaining insights into their dispersal patterns, evolutionary genetics, emergence and reemergence in different communities and catchments poses a great challenge for molecular epidemiologists. Multiple ge- nome sequences from across strains of a single species offer more fine scale resolu- tion of genetic differences that enable tracking and identification of species and development of additional genetic mark- ers. Prokaryotes evolve largely by horizontal gene acquisition, vertical genome reduc- tion and in-situ gene duplication strategies to shape an optimal repertoire of the genes and elements to support a successful lifestyle [7]. Lateral gene flow is wide- spread among different strains of a single species and most bacterial organisms acquire novel functions through harness- ing functional attributes of some of the genes gained through such recombination- al processes. One important message that has emerged from the analyses of complete genomes is–microbes are diverse and highly adaptable. To know why it is so, we need further insights through individ- ual and community level genomics. Such federated genomics approaches are also likely to help us answer several outstand- ing questions such as, how virulence evolves as a function of genome optimiza- tion under different compulsions offered by a colonized niche; how microbes PLoS ONE | www.plosone.org 2 June 2009 | Volume 4 | Issue 6 | e5831