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Studying   population   dynamics   and   their   impact   on   evolutionary   processes   in   microorganisms  such  as  bacteria  is  challenging.  Evolution  is  the  result  of  random   mutations  and  selection  under  given  environmental  conditions.  Environments  are   composed  of  abiotic  and  biotic  factors  and  how  an  environment  changes  over  time   is   presumably   unpredictable   (Lewontin,   1966;   Beatty   &   Desjardins,   2009).   The   surrounding   environment   of   an   organism   is   dynamic   and   constantly   changing,  

with  consequences  for  evolutionary  outcomes  (Franke  et  al.,  2011).  The  aim  of  this   study   was   to   obtain   information   about   the   impact   of   population   composition   on   switcher   evolution   and   how   population   dynamics   change   during   evolution   depending   on   historical   genotypes   that   occurred   along   the   evolutionary   path   in   Line  1.    

Earlier  genotypes  (SBW25,  1s1,  1s2)  are  less  likely  to  produce  a  switcher  genotype   than  genotypes  that  appeared  at  a  later  stage  along  the  evolutionary  history  (1s3,   1s4;  Fig.  5.3).  In  addition  to  the  number  of  observed  switchers,  the  total  number  of   new  types,  the  proportion  of  new  types  in  the  total  population,  cell  densities  and   phenotypic   diversity   (number   of   different   colony   morphotypes)   within   a   microcosm   were   recorded   for   each   replicate   to   get   an   estimate   of   how   the   population   compositions   developed   within   three   days   of   growth   and   diversification   in   a   static   environment.   As   has   been   pointed   out   earlier,   SBW25,   1s1  and  1s2  evolved  faster  than  did  1s3  and  1s4.  Nearly  all  replicates  of  SBW25,   1s1   and   1s2   produced   a   new   phenotype   within   the   first   three   days   in   a   static   microcosm   (Fig.   5.4).   In   addition,   new   types   were   able   to   reach   high   cell   frequencies   (Fig.   5.5),   indicating   that   some   new   variants   had   a   substantial   advantage   under   these   conditions.   At   the   same   time   the   likelihood   of   switcher   occurrence  decreased  (Fig.  5.6).  It  has  been  shown  that  genetic  constraints  in  1s1   and   1s2   are   likely   to   limit   the   evolution   of   a   switcher   (Fig.   5.1),   perhaps   due   to   negative  genetic  interactions  (Khan  et  al.,  2011).  In  SBW25  however  it  is  possible   that   the   variety   of   ecological   interactions   between   the   many   different   types   that   appeared   quite   quickly   decrease   the   likelihood   of   switcher   occurrence.   For   example,   strong   competition   for   the   air-­‐liquid   interface   may   have   prevented   the   establishment  of  a  switcher  genotype  within  the  population.    

The   comparison   of   the   different   founder   populations   shows   that   diversity   was   lower   in   1s3   and   1s4   than   in   the   genotypes   SBW25,   1s1   and   1s2   (Fig.   5.7).   Low   frequency  of  new  types  and  lower  diversity  after  diversification  of  genotypes  that   occurred  later  along  the  evolutionary  pathway  suggest  that  the  supply  of  beneficial   mutations   was   higher   in   the   beginning   and   decreased   over   time   (Lenski   &   Travisano,   1994;   Arjan  et   al.,   1999).   Due   to   the   increased   supply   of   beneficial   mutations   many   different   novel   types   evolved   simultaneously   (McDonald   et   al.,  

2009;  Sniegowski  &  Gerrish,  2010)  in  the  beginning  and  prevented  any  switcher   mutation   that   might   have   occurred   of   becoming   established   in   the   population.   Later   on   the   rate   of   beneficial   mutations   decreased,   which   may   explain   the   increased  number  of  transfers  that  were  needed  to  detect  a  new  type  in  1s3  and   1s4.  The  lack  of  beneficial  mutations,  on  the  other  hand,  might  have  increased  the   chance   of   switcher   mutations   becoming   fixed   within   populations   of   1s3   and   1s4   before   another   beneficial   mutation   arose.   Here   timing   of   occurrence   of   the   switcher   mutation   determines   the   success   of   the   novel   phenotype   (Hegreness  et   al.,  2006).  The  lack  of  beneficial  mutations  can  have  different  causes.  As  addressed   earlier,   the   high   fitness   of   1s3   and   1s4   because   of   cellulose   production   might   decrease   the   chances   of   mutations   that   imply   only   a   small   benefit   (e.g.   weak   biofilm).  Alternatively,  common  evolutionary  routes  might  become  depleted  over   the   course   of   evolution.   Other   mutational   pathways   that   can   improve   the   performance  under  present  environmental  circumstances  have  to  be  found,  which   may  take  a  longer  time.  This  will  be  discussed  in  more  detail  in  the  next  section.    

 

5.4.3.1.1      Depletion  of  evolutionary  pathways  with  proceeding  evolution    

 

The  capacity  to  evolve  a  switcher  based  on  carB*  has  been  shown  to  exist  in  the   ancestor   SBW25.   Here  carB*   had   a   positive   effect   on   fitness,   indicating   that   a   switcher   can   increase   in   frequency   within   a   SBW25   population   (Fig.   5.1).   This   raises   the   question   as   to   why   no   switcher   was   found   in   the   first   selection   round   during  the  REE  in  any  of  the  12  parallel  lineages,  since  they  started  from  the  same   ancestor.    

The   evolutionary   history   of   Line   1   (Tab.   5.1)   is   the   result   of   evolution   in   two   alternating  environments,  static  and  shaken,  starting  from  the  common  ancestor  P.   fluorescens  SBW25.  It  is  known  that  P.  fluorescens  SBW25  diversifies  quickly  when   growing  in  a  static  KB  filled  microcosm  (Rainey  &  Travisano,  1998).  Within  hours   usually,   WS   types   arise   as   a   consequence   of   an   oxygen   gradient   that   develops   within  the  media.  The  WS  types  are  able  to  colonise  the  air-­‐liquid  interface  due  to   biofilm  formation,  which  is  the  result  of  the  overproduction  of  a  cellulosic  polymer  

(Spiers  et  al.,   2003;   Rainey   &   Travisano,   2003).   The   transfer   of   a   WS   type   into   a   shaken   environment   generally   causes   the   reversal   to   an   ancestral-­‐like   SM   type   (Koza  et  al.,  2011).  Suppressor  analysis  of  novel  genotypes  that  evolved  during  the   course  of  the  REE  in  the  12  replicate  lineages  identified  important  common  genetic   pathways   that   underlie   the   evolution   of   WS   and   SM   types.   In   many   cases   novel   types   showed   mutations   in  wsp,  wss,  aws   and  mws  (see   Chapter   1,   section   1.4.3;   Kahn  et  al.,   1998;   Bantinaki,   2001;   Spiers  et  al.,   2002;   Spiers  et  al.,   2003;   Gehrig,   2005;   McDonald   et   al.,   2009).   Noteworthy   is   the   modular   nature   of   mutation   occurrences  in  all  12  lineages,  such  as  that  one  mutation  induces  the  synthesis  of  a   cellulosic   polymer   under   static   conditions   followed   by   a   mutation   in   the   same   locus  that  turns  off  the  production  under  shaken  conditions.  For  example  in  Line  1   the   first   mutation   appeared   in   mwsR   and   led   to   a   WS   type   (Tab.   5.1).   The   subsequent  mutation  took  place  again  in  mwsR  and  caused  a  SM-­‐like  phenotype.  In   the  next  selection  round  the  WS  type  was  induced  by  a  mutation  in  aws.  After  the   change  to  a  shaken  environment  another  mutation  in  aws  caused  the  reversal  to   the   SM   type.   This   modularity   was   not   observed   for   the   fifth   and   sixth   mutations   (wspF   and  wssA),   but   after   that   was   observed   again   for   the   seventh   and   eighth   mutations,  which  occurred  in  mwsR  (Tab.  5.1).  Although  the  modular  organisation   was  interrupted  by  mutations  in  wspF  followed  by  wssA,  they  still  represent  two   out  of  four  common  mutational  pathways  involved  in  WS  and  SM  evolution  (Tab.   5.1).    

The   switcher   genotype   was   detected   during   the   ninth   selection   round   and   had   a   mutation   in  carB,   which   was   not   involved   in   any   of   the   phenotypic   changes   that   occurred   previously.   Other   studies   found   a   correlation   between   the   fitness   of   a  

carB*   mutation   and   the   proportion   of   WS   types   (Gallie,   2009).   For   example   the   fitness   benefit   of  carB*   in   SBW25   decreased   when   competition   between   SBW25   and   SBW25carB*   took   place   over   72   hours   instead   of   48   hours,   due   to   the   occurrence  of  novel  WS  types.  This  fitness  decrease  was  not  observed  in  1s4  after   72  hours  because  evolution  was  much  slower.  It  was  suggested  that  many  of  the   common  mutational  routes  that  can  lead  to  a  WS  type  (wsp,  wss,  aws  and  mws)  are   available   in   genotypes   that   evolved   during   earlier   selection   rounds   (e.g.   SBW25,   1s1,   1s2).   With   proceeding   evolution   these   common   pathways   are   gradually  

removed  due  to  mutations  and  are  therefore  not  available  in  1s4  for  WS  evolution   (Gallie,   2009).   The   depletion   of   common   mutational   pathways   over   time   may   explain  the  increased  duration  of  evolution,  the  reduced  proportion  of  novel  types,   the  decreased  diversity  that  was  observed  during  the  SREE  in  1s3  and  1s4  in  this   study,   and   an   elevated   likelihood   of   switcher   emergence   (Arjan   et   al.,   1999).   Recently,  most  of  the  mutational  pathways  of  all  12  replicate  P.  fluorescens  lineages   have  been  identified.  The  data  suggest  that  the  overlap  in  genetic  changes  is  higher   in   the   beginning   of   the   evolutionary   pathways   and   that   lineages   tend   to   have   mutations   in   more   diverse   loci   the   longer   they   evolve   (data   not   published).   This   suggests  that  after  common  mutational  pathways  have  been  used  (McDonald  et  al.,   2009),   less   likely   and   more   diverse   mutational   pathways   can   arise   that   increase   the  chance  of  survival  in  that  particular  environment.  It  has  been  suggested  that   common   mutational   targets,   because   of   genetic   architecture   and   functionalities,   have  a  higher  rate  of  being  translated  into  adaptive  phenotypic  change  (McDonald   et  al.,  2009).  This  may  explain  the  high  number  and  the  fast  evolution  of  new  types   in   SBW25,   1s1   and   1s2,   where   more   of   these   common   mutational   pathways   are   still  available,  however  it  remains  curious  that  some  pathways  such  mwsR  can  be   used  more  than  once  in  the  evolution  of  a  WS  (Tab.  5.1).  

   

5.4.4 Comparison  of  theoretical  capacity  of  switcher  evolution  and  

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