ronmental condition or mecha-nism of motility (Fig. 1). Link-ing structural changes at the protein and network levels to re-sponse dynamics and physiolo-gy requires a combined effort of modeling and experimentation.Modeling studies based on thework of Wuichet and Zhulinwill lead to the generation of hypotheses regarding responsedynamics in chemotaxis and will guide experimental work inspecies beyond the typical mod-el organisms. The value of suchguidance is clear, consideringthat the detailed knowledge of chemotaxis networks in theseorganisms took many decadesto accumulate.To date, research in evolu-tionary systems biology em- ploys two main approaches. Onthe one hand are comparativegenomics approaches such asthat used by Wuichet and Zhulin. These provide insightsinto differences among organ-isms at the genetic level, whichwe can then try to interpret atthe network level as changes inconnectivity. When applied inthe context of gene regulatorynetworks (
), comparativegenomics played an importantrole in achieving a global under-standing of how the evolution of these systems links to changesin development (
). On theother hand, a more bottom-upapproach aims to directly ex- plore the evolution of biologicalsystems in silico. By allowingmodels derived from first prin-ciples to “evolve” in the computer (
)or by exploring the space of possible mod-els (
), these studies allow us toidentify evolutionary processes and envi-ronmental conditions that can lead to spe-cific functional and structural features in biological networks. The two approachesare complementary; the former can help toidentify the common genetic innovationsselected for by evolution, whereas the latter can help to discern the links between plau-sible selective pressures at the organismlevel and the resulting effects on responsedynamics and structure at the network lev-el. Combining these two approaches so thatevolutionary simulations incorporate datafrom genomic and experimental studies[for example, using an experimentally veri-fied network as a starting point for an evo-lutionary simulation (
)] will be an excit-ing avenue for future research.Evolution drives change in all biologi-cal systems. Those changes that are neutralor adaptive under the conditions experi-enced by the organism might persist in the population, leading to diversity (
) and complexity (
) at the network level that isnot present in similar human-made sys-tems. If there are any design principlesthat provide a unifying pattern underneathsuch complexity and diversity, decipheringthem requires a firm understanding of theeffects of evolutionary processes at thenetwork level.
References and Notes
1.K.Wuichet, I.B.Zhulin, Origins and diversificationof a complex signal transduction system inprokaryotes.
, ra50 (2010).2.H.C.Berg, D.A.Brown, Chemotaxis in
Es- cherichia coli
analyzed by three-dimensionaltracking.
, 55–78 (1974).3.D.Bray, M.D.Levin, K.Lipkow, The chemotacticbehavior of computer-based surrogate bacteria.
, 12–19 (2007).4.R.Schmitt, Sinorhizobial chemotaxis:A departurefrom the enterobacterial paradigm.
, 627–631 (2002).5.S.L.Porter, G.H.Wadhams, J.P.Armitage,Rhodobacter sphaeroides:Complexity in chemo-tactic signalling.
, 251–260(2008).6.R.Hamer, P.Y.Chen, J.P.Armitage, G.Reinert,C.M.Deane, Deciphering chemotaxis pathwaysusing cross species comparisons.
, 3 (2010).7.P.Cluzel, M.Surette, S.Leibler, An ultrasensitive
T u m b l i n g R a t e T u m b l i n g R a t e T u m b l i n g R a t e
(+) Attractant (-) Time(+) Attractant (-) Time(+) Attractant (-)
Motility machineryReceptor complexCheBCheACheYCheRCheZ
A cartoon representation of sample chemotaxis networks and their dynamics in bacteria living un-der different conditions and possessing different motility machinery.All motile bacteria possess a signal-ing network to regulate their motility behavior and to achieve chemotaxis.This network is composed of sixregulatory proteins in the model organism
:a receptor complex for sensing chemoattrac-tants, two proteins (CheR and CheB) that regulate receptor activity, a histidine kinase (CheA), a responseregulator (CheY), and its phosphatase (CheZ) that acts on the response regulator.Genomic analyseshave revealed that chemotaxis networks show substantial diversity, in terms of both structure and proteincontent, across the bacterial kingdom.This diversity is a result of evolution;depending on their life-style,environment, and motility machinery, bacteria have evolved different signaling networks to achieve re-sponse dynamics and chemotaxis behavior suitable for those conditions (note that the tree shown is rep-resentative and does not reflect phylogeny of any particular species).The differences in response dynam-ics are depicted in the cartoon by the response of the network to addition and subtraction (indicated bydown and up arrows, respectively) of a chemoattractant to the media.
.org29June 2010Vol 3 Issue 128 pe23