November 29, 2005, 11:00 am @ Building 38A, B2 library

 

Using Comparative Genomics to Understand Bacterial Signal Transduction Networks:

Bacterial IQ, Introverts and Extroverts 

 

Michael Galperin 

 

The complexity of signal transduction systems, even in classical model microorganisms such as Escherichia coli, Bacillus subtilis or yeast, has long hindered their systematic analysis. The availability of complete genome sequences has changed that by allowing us to predict all regulatory components in a given organism, compare their organization in various organisms, and reveal how much we still do not know about microbial signal transduction. One of the major findings of comparative genomics was that microbial signaling systems are far more diverse than previously expected and include sensor histidine kinases, methyl-accepting chemotaxis receptors, Ser/Thr/Tyr protein kinases and protein phosphatases, adenylate and diguanylate cyclases and phosphodiesterases. Output domains of response regulators, besides a variety of DNA-binding domains, include RNA-binding, enzymatic and protein-protein interaction domains. There is a significant degree of cross-talk between various signal transduction systems. From the practical point of view, the diversity of multidomain signal transduction proteins poses a significant challenge to genome annotation and results in a large number of erroneous (or incomplete) assignments in almost every microbial genome. On the other hand, detailed analysis of such proteins often results in discovery of new protein domains.

I will discuss the history and recent progress in studying c-di-GMP, a new secondary messenger in bacteria, and our recent work on the identification of the c-di-GMP-binding protein. I will also present the results of a comprehensive census of signal transduction proteins encoded in complete genomes of 200 bacterial and archaeal species, sequenced by the end of September 2005. The census data showed uneven distribution of most signaling proteins among bacterial and archaeal phyla. The total number of signal transduction proteins grows approximately as a square of genome size. While histidine kinases are found in representatives of all phyla and are distributed according to the power law, other signal transducers have a patchy distribution. Still, abundance of any given system generally correlates with the organism's heritage and lifestyle. I suggest using the fraction of signal transducers in the total protein set as a measure of the organism's ability to survive in diverse conditions, the 'bacterial IQ', while the ratio of transmembrane receptors to intracellular sensors can define whether the organism is an 'extrovert', actively sensing the environmental parameters, or an 'introvert', more concerned about its internal homeostasis. Microorganisms with the highest IQ, including the current leader Wolinella succinogenes, are often found among the poorly studied beta-, delta- and epsilon-proteobacteria. Among all bacterial phyla, only cyanobacteria appear to be true introverts, probably due to their capacity to conduct oxygenic photosynthesis. The census data can be used to get an insight into the metabolic and behavioral propensities of each given organism and improve prediction of the organism's properties based solely on its genome sequence.