title: Macromolecular networks and intelligence in microorganisms.
abstract: Living organisms persist by virtue of complex interactions among many components organized into dynamic, environment-responsive networks that span multiple scales and dimensions. Biological networks constitute a type of information and communication technology (ICT): they receive information from the outside and inside of cells, integrate and interpret this information, and then activate a response. Biological networks enable molecules within cells, and even cells themselves, to communicate with each other and their environment. We have become accustomed to associating brain activity - particularly activity of the human brain - with a phenomenon we call "intelligence." Yet, four billion years of evolution could have selected networks with topologies and dynamics that confer traits analogous to this intelligence, even though they were outside the intercellular networks of the brain. Here, we explore how macromolecular networks in microbes confer intelligent characteristics, such as memory, anticipation, adaptation and reflection and we review current understanding of how network organization reflects the type of intelligence required for the environments in which they were selected. We propose that, if we were to leave terms such as "human" and "brain" out of the defining features of "intelligence," all forms of life - from microbes to humans - exhibit some or all characteristics consistent with "intelligence." We then review advances in genome-wide data production and analysis, especially in microbes, that provide a lens into microbial intelligence and propose how the insights derived from quantitatively characterizing biomolecular networks may enable synthetic biologists to create intelligent molecular networks for biotechnology, possibly generating new forms of intelligence, first in silico and then in vivo.
authors.affiliation: Department of Molecular Cell Physiology, Vrije Universiteit Amsterdam Amsterdam, Netherlands ; Manchester Centre for Integrative Systems Biology, The University of Manchester Manchester, UK ; Synthetic Systems Biology, University of Amsterdam Amsterdam, Netherlands.
authors.forename: Hans V
authors.initials: HV
authors.lastname: Westerhoff
authors.affiliation: Institute for Systems Biology Seattle, WA, USA ; Molecular and Cellular Biology Program, University of Washington Seattle, WA, USA.
authors.forename: Aaron N
authors.initials: AN
authors.lastname: Brooks
authors.affiliation: Institute for Systems Biology Seattle, WA, USA ; Luxembourg Centre for Systems Biomedicine, University of Luxembourg Esch-sur-Alzette, Luxembourg.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Simeonidis
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología Mexico City, Mexico.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: García-Contreras
authors.affiliation: Department of Automatic Control and Systems Engineering, The University of Sheffield Sheffield, UK.
authors.forename: Fei
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Molecular Cell Physiology, Vrije Universiteit Amsterdam Amsterdam, Netherlands.
authors.forename: Fred C
authors.initials: FC
authors.lastname: Boogerd
authors.affiliation: School of Computer Science, The University of Manchester Manchester, UK.
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Jackson
authors.affiliation: Netherlands Institute for Neuroscience Amsterdam, Netherlands ; Russian Cardiology Research Center Moscow, Russia ; Department of Medicine, Center for Alzheimer and Neurodegenerative Research, University of Alberta Edmonton, AB, Canada.
authors.forename: Valeri
authors.initials: V
authors.lastname: Goncharuk
authors.affiliation: Institute for Systems Biology Seattle, WA, USA ; Luxembourg Centre for Systems Biomedicine, University of Luxembourg Esch-sur-Alzette, Luxembourg.
authors.forename: Alexey
authors.initials: A
authors.lastname: Kolodkin
keywords: anticipation; association; decision-making; emergence; microbial intelligence; problem solving; robust adaptation; self-awareness
references.citation: DNA Cell Biol. 2009 Aug;28(8):405-11
references.pmid: 19485767
references.citation: Nat Rev Genet. 2007 Jun;8(6):450-61
references.pmid: 17510665
references.citation: Science. 2005 Apr 1;308(5718):83-8
references.pmid: 15746389
references.citation: Trends Microbiol. 2001 May;9(5):206-8
references.pmid: 11336835
references.citation: PLoS Comput Biol. 2011 Jun;7(6):e1002063
references.pmid: 21738455
references.citation: Nat Rev Mol Cell Biol. 2009 Jun;10(6):410-22
references.pmid: 19461664
references.citation: Behav Neurosci. 1994 Feb;108(1):94-9
references.pmid: 8192854
references.citation: Cell. 2011 Feb 18;144(4):590-600
references.pmid: 21335240
references.citation: Science. 2013 Sep 6;341(6150):1241214
references.pmid: 24009397
references.citation: Annu Rev Microbiol. 1995;49:711-45
references.pmid: 8561477
references.citation: Microbiol Mol Biol Rev. 2013 Dec;77(4):628-95
references.pmid: 24296575
references.citation: BMC Syst Biol. 2013 Nov 21;7:131
references.pmid: 24261908
references.citation: Biosystems. 2008 Oct-Nov;94(1-2):34-46
references.pmid: 18619513
references.citation: J Theor Biol. 1991 Nov 21;153(2):255-85
references.pmid: 1686290
references.citation: Nat Rev Microbiol. 2010 Jan;8(1):39-50
references.pmid: 19966815
references.citation: Nat Biotechnol. 2000 May;18(5):533-7
references.pmid: 10802621
references.citation: J Theor Biol. 2003 Jul 21;223(2):149-60
references.pmid: 12814598
references.citation: Curr Opin Microbiol. 2008 Dec;11(6):553-9
references.pmid: 18955155
references.citation: Biotechnol Adv. 2000 Jul;18(4):267-88
references.pmid: 14538104
references.citation: Front Physiol. 2012 Jul 23;3:291
references.pmid: 22934043
references.citation: FEBS J. 2013 Jan;280(1):160-73
references.pmid: 23121761
references.citation: Cell. 2012 Mar 16;148(6):1258-70
references.pmid: 22424233
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2004 Sep;70(3 Pt 1):031909
references.pmid: 15524551
references.citation: Commun Integr Biol. 2010 Jul;3(4):374-8
references.pmid: 20798831
references.citation: Prog Biophys Mol Biol. 2013 Apr;111(2-3):69-74
references.pmid: 23103359
references.citation: FEMS Microbiol Rev. 1995 Jul;16(4):309-21
references.pmid: 7654406
references.citation: Nat Rev Neurosci. 2013 Jun;14(6):417-28
references.pmid: 23635870
references.citation: Adv Appl Microbiol. 2011;75:111-43
references.pmid: 21807247
references.citation: Cell. 2007 Dec 28;131(7):1354-65
references.pmid: 18160043
references.citation: Annu Rev Microbiol. 2008;62:193-210
references.pmid: 18537474
references.citation: Nat Rev Neurosci. 2012 Oct;13(10):701-12
references.pmid: 22968153
references.citation: Eur J Pharm Sci. 2012 Jul 16;46(4):190-7
references.pmid: 21704158
references.citation: ISME J. 2008 Dec;2(12):1171-82
references.pmid: 18633449
references.citation: Commun Integr Biol. 2010 Nov;3(6):540-4
references.pmid: 21331234
references.citation: Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19775-80
references.pmid: 23150539
references.citation: Science. 1957 Feb 1;125(3240):191-2
references.pmid: 13390982
references.citation: Proc Natl Acad Sci U S A. 1975 Aug;72(8):3235-9
references.pmid: 1103143
references.citation: Mol Cell. 2006 Jun 9;22(5):701-7
references.pmid: 16762842
references.citation: Nature. 2005 May 5;435(7038):118-22
references.pmid: 15875027
references.citation: Microbiology (Reading). 2004 Nov;150(Pt 11):3731-3739
references.pmid: 15528659
references.citation: J Comp Physiol Psychol. 1952 Feb;45(1):58-65
references.pmid: 14907934
references.citation: Prog Nucleic Acid Res Mol Biol. 2005;79:1-48
references.pmid: 16096026
references.citation: Nature. 2014 Jan 30;505(7485):681-685
references.pmid: 24336212
references.citation: PLoS Pathog. 2013 Jan;9(1):e1003108
references.pmid: 23300457
references.citation: Oncogene. 2007 May 14;26(22):3254-66
references.pmid: 17496920
references.citation: Cogn Process. 2006 Mar;7(1):11-29
references.pmid: 16628463
references.citation: Nature. 1999 Jan 14;397(6715):168-71
references.pmid: 9923680
references.citation: J Math Biol. 2009 Jan;58(1-2):7-34
references.pmid: 18278498
references.citation: Front Microbiol. 2013 Aug 19;4:229
references.pmid: 23966987
references.citation: Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4649-53
references.pmid: 10781070
references.citation: J Theor Biol. 2002 Jan 7;214(1):17-29
references.pmid: 11786029
references.citation: Antioxid Redox Signal. 2006 Sep-Oct;8(9-10):1651-65
references.pmid: 16987019
references.citation: J Biol Chem. 2002 Mar 22;277(12):9625-8
references.pmid: 11779877
references.citation: Best Pract Res Clin Gastroenterol. 2013 Feb;27(1):73-83
references.pmid: 23768554
references.citation: Eur J Biochem. 2002 Mar;269(6):1662-9
references.pmid: 11895436
references.citation: Annu Rev Cell Dev Biol. 2005;21:319-46
references.pmid: 16212498
references.citation: Nature. 2002 Feb 21;415(6874):841
references.pmid: 11859344
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):11980-5
references.pmid: 14530388
references.citation: PLoS Comput Biol. 2012;8(11):e1002739
references.pmid: 23133353
references.citation: J Bacteriol. 2001 Aug;183(16):4914-7
references.pmid: 11466297
references.citation: Trends Microbiol. 2004 Aug;12(8):366-72
references.pmid: 15276612
references.citation: Wiley Interdiscip Rev Syst Biol Med. 2011 Sep-Oct;3(5):544-61
references.pmid: 21197660
references.citation: Nat Methods. 2013 May;10(5):413-20
references.pmid: 23524393
references.citation: BMC Bioinformatics. 2006 Jun 02;7:280
references.pmid: 16749936
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):228-33
references.pmid: 19966295
references.citation: Biol Chem. 2000 Sep-Oct;381(9-10):965-72
references.pmid: 11076029
references.citation: Science. 2002 Jul 12;297(5579):211-8
references.pmid: 12040087
references.citation: FEMS Microbiol Rev. 2008 Aug;32(5):723-35
references.pmid: 18549407
references.citation: Zh Obshch Biol. 2009 May-Jun;70(3):225-38
references.pmid: 19530599
references.citation: Contrib Microbiol. 2009;16:18-32
references.pmid: 19494577
references.citation: FEBS Lett. 2001 Jul 6;500(3):169-71
references.pmid: 11445079
references.citation: RNA Biol. 2013 Mar;10(3):347-52
references.pmid: 23392242
references.citation: Nat Commun. 2013;4:1792
references.pmid: 23653204
references.citation: Front Microbiol. 2014 Jun 11;5:270
references.pmid: 24966852
references.citation: Neuron. 2012 Jun 21;74(6):970-4
references.pmid: 22726828
references.citation: Science. 2008 Jun 6;320(5881):1313-7
references.pmid: 18467556
references.citation: Trends Microbiol. 2003 Jul;11(7):330-7
references.pmid: 12875817
references.citation: Annu Rev Microbiol. 2004;58:75-98
references.pmid: 15487930
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6327-32
references.pmid: 19369215
references.citation: Science. 2002 Mar 1;295(5560):1664-9
references.pmid: 11872830
references.citation: Nature. 2000 Aug 31;406(6799):959-64
references.pmid: 10984043
references.citation: Nature. 2008 Nov 27;456(7221):516-9
references.pmid: 18971928
references.citation: Proc Natl Acad Sci U S A. 1982 Apr;79(8):2554-8
references.pmid: 6953413
references.citation: Science. 2007 Jul 27;317(5837):526-9
references.pmid: 17569828
references.citation: Curr Opin Microbiol. 2004 Oct;7(5):505-12
references.pmid: 15451506
references.citation: Microbiology (Reading). 2004 Apr;150(Pt 4):831-841
references.pmid: 15073293
references.citation: Ann Neurosci. 2010 Jul;17(3):136-41
references.pmid: 25205891
references.citation: FEMS Microbiol Lett. 2012 Nov;336(1):38-44
references.pmid: 22861498
references.citation: Microbes Infect. 2009 May-Jun;11(6-7):637-45
references.pmid: 19348960
references.citation: Microbiology (Reading). 2010 Aug;156(Pt 8):2271-2282
references.pmid: 20488878
references.citation: PLoS Comput Biol. 2013;9(8):e1003179
references.pmid: 23990765
references.citation: Nat Rev Neurol. 2010 Nov;6(11):611-23
references.pmid: 21045795
references.citation: BMC Evol Biol. 2011 Feb 14;11:45
references.pmid: 21320320
references.citation: Nat Biotechnol. 2009 Aug;27(8):753-9
references.pmid: 19648908
references.citation: J Theor Biol. 2008 Jun 7;252(3):555-67
references.pmid: 18222488
references.citation: Biosystems. 2010 Jan;99(1):27-41
references.pmid: 19686801
references.citation: Nat Rev Microbiol. 2008 Jun;6(6):466-76
references.pmid: 18461074
references.citation: Genetics. 1998 Aug;149(4):1633-48
references.pmid: 9691025
references.citation: PLoS Genet. 2011 Nov;7(11):e1002353
references.pmid: 22102822
references.citation: ISME J. 2012 Jul;6(7):1356-66
references.pmid: 22237540
references.citation: Proc Natl Acad Sci U S A. 2012 Sep 18;109(38):15277-82
references.pmid: 22927389
references.citation: BMC Microbiol. 2007 May 18;7:42
references.pmid: 17511876
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20705-10
references.pmid: 19098103
references.citation: FEBS J. 2005 Apr;272(8):1965-85
references.pmid: 15819889
references.citation: Proc Biol Sci. 2013 Jun 12;280(1764):20131055
references.pmid: 23760867
references.citation: Appl Environ Microbiol. 2006 Jun;72(6):3805-13
references.pmid: 16751484
references.citation: Science. 2008 Jan 25;319(5862):482-4
references.pmid: 18218902
references.citation: Neurosci Biobehav Rev. 2009 Mar;33(3):383-93
references.pmid: 19046987
references.citation: PLoS Comput Biol. 2008 Jan;4(1):e1
references.pmid: 18179279
references.citation: FEBS Lett. 2011 Jan 3;585(1):23-8
references.pmid: 21134373
references.citation: Biol Chem. 2000 Sep-Oct;381(9-10):911-20
references.pmid: 11076022
references.citation: Stud Hist Philos Biol Biomed Sci. 2007 Dec;38(4):775-9
references.pmid: 18053932
references.citation: Cell. 2009 Jul 10;138(1):160-71
references.pmid: 19596242
references.citation: ISME J. 2012 Jul;6(7):1336-44
references.pmid: 22237544
references.citation: Science. 2002 Oct 25;298(5594):824-7
references.pmid: 12399590
references.citation: Mol Syst Biol. 2011 Apr 12;7:483
references.pmid: 21487402
references.citation: Biophys Chem. 2000 May 15;84(3):195-204
references.pmid: 10852307
references.citation: ISME J. 2011 Dec;5(12):1857-70
references.pmid: 21677694
references.citation: Cell. 2009 Aug 21;138(4):760-73
references.pmid: 19703401
references.citation: Commun Integr Biol. 2012 Jan 1;5(1):3-11
references.pmid: 22482001