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3 PROYECTOS DE RESPONSABILIDAD SOCIAL EN EL FONDO

3.5 PROYECTOS FOEMETCOL AÑO 2010

the  same  gene  (carB).  

3. To  test  whether  ecological  interactions  have  an  impact  on  the  likelihood  of   switcher   evolution   in   genotypes   from   different   evolutionary   time   points.   Here,  variation  in  the  number  of  re-­‐evolved  switchers  should  be  linked  to  a   change  in  population  composition  (i.e.  number  of  new  variants,  cell  density,   diversity)  over  evolutionary  time.    

 

5.2

Summary  of  materials  and  methods    

 

5.2.1 Experimental  design  of  the  SREE  in  Line  1    

Experimental  conditions  of  the  SREE  were  based  on  the  experimental  design  of  the   original  REE  and  followed  the  same  experimental  guidelines  (see  section  1.4.4).  In   summary,  during  the  REE  bacterial  cultures  were  grown  for  three  days  in  one  of   the   selective   environments,   static   or   shaken,   which   marked   one   selection   round.   After  three  days  the  bacterial  cultures  were  plated  and  screened  for  a  new  colony   morphology  type.  The  most  abundant  new  type  was  selected  for  the  inoculation  of   a   new   microcosm,   which   was   then   kept   under   the   opposite   environmental   condition   than   that   in   which   it   had   evolved   (the   next   selection   round).   This   was   repeated  for  several  selection  rounds,  with  an  alternation  between  a  static  and  a   shaken   environment   for   each   selection   round.   In   cases   when   no   new   type   was   detected,   a   small   amount   of   culture   was   transferred   into   a   new   microcosm   and   kept   for   another   three   days   under   the   same   environmental   condition   (first   transfer,  same  selection  round).  This  was  repeated  until  a  new  type  was  detected   on  agar  plates  (several  transfers  in  one  selection  round).  The  appearance  of  a  type   with  novel  colony  morphology  marked  the  end  of  a  selection  round.  

In   this   study   a   replay   experiment   (SREE)   was   performed   from   different   starting   positions   (evolutionary   time   points)   in   Line   1.   The   SREE   was   carried   out   to   test   whether  the  evolution  of  a  switcher  genotype  is  equally  likely  from  any  genotype  

that  evolved  at  different  time  points  during  the  course  of  evolution  or  whether  the   eight   preceding   mutations   that   were   present   in   1s4   (immediate   ancestor   of   the   original   switcher   in   the   REE)   are   essential.   The   switcher   in   the   REE   occurred   in   Line  1  and  Line  6  after  eight  rounds  of  selection  (see  section  1.5).  The  focus  of  this   study   is   on   Line   1   as   it   has   been   characterised   and   studied   to   a   great   extent   in   previous   studies   (Beaumont   et   al.,   2009;   Gallie,   2009).   The   switcher   in   Line   1   (1w4)  evolved  in  a  static  environment  from  1s4.    

 

Table  5.1:  Mutational  history  of  the  switcher  (1w4)  in  Line  1.  Evolutionary  history  of   the   switcher   in   Line   1   is   composed   of   nine   mutations,   including   the   switcher   mutation  

carB*   (last   column).   Mutations   that   occurred   during   history   occurred   in   genes   that   are   involved  in  the  regulation  of  cellulose  synthesis  due  to  selection  in  a  static  or  in  a  shaken   environment.   The   founder   populations   were   genotypes   that   would,   according   to   the   experimental   design   of   the   REE,   go   into   a   static   environment   in   the   following   selection   round   (“s”   genotypes;   bold)   because   the   original   switcher   (1w4)   evolved   under   static   conditions.  

Number  of  

mutations   1   2   3   4   5   6   7   8   9  

Environment   static   shaken   static   shaken   static   shaken   static   shaken   static  

Name   1w0   1s1   1w1   1s2   1w2   1s3   1w3   1s4   1w4  

Mutational  

History   mwsR   mwsR   awsX   awsR   wspF   wssA   mwsR   mwsR   carB*  

   

For  that  reason  five  genotypes  that  occurred  during  the  REE  in  Line  1  and  would   grow   according   to   the   rules   of   the   REE   in   the   next   selection   round   in   a   static   environment   were   selected   (Tab.   5.1;   SBW25,   1s1,   1s2,   1s3,   and   the   immediate   ancestor   1s4).   The   strains   were   revived   on   KB   agar   plates   from   a   frozen   stock   culture.    

The  experiment  was  divided  into  three  experimental  blocks  with  20  replicates  of   each  strain  in  each  block  (60  replicate  microcosms  in  total  for  each  lineage).  For   one   biological   replicate   a   single   colony   was   picked   from   the   agar   plate   and   transferred  into  6  ml  liquid  KB  media.  After  growing  overnight,  6  µl  of  each  culture  

for  three  days  (one  selection  round).  After  three  days  the  cultures  were  thoroughly   vortexed,  diluted  and  spread  on  KB  agar  plates  (Fig.  5.2).    

 

Figure   5.2:   Experimental   design   of   the   SREE.   Overnight   cultures   of   SBW25,   1s1,   1s2,   1s3  and  1s4  acted  as  founder  populations  to  replay  the  evolution  of  phenotypic  switching   under  static  conditions  (60  microcosms  per  lineage).  After  three  days’  growth  in  a  static   microcosm  the  cultures  were  diluted,  plated  and  screened  for  new  colony  types.  If  a  new   type  or  a  switcher  (new/SW)  was  detected  the  replicate  was  terminated.  Switchers  were   stored  at  –80°C.  If  no  new  type  was  detected  6  µl  of  the  culture  were  transferred  to  a  new   microcosm   and   incubated   for   another   three   days   under   static   conditions   before   being   diluted,  plated  and  screened  for  new  types  again.  This  process  was  repeated  until  a  new   type  was  found.    

 

The  OD600  was  randomly  measured  for  two  to  three  microcosms  in  each  strain  to  

estimate  the  plating  volume  that  was  needed  for  four  plates  to  be  able  to  screen   approximately  500-­‐1000  colonies.  After  two  days  all  plates  were  screened  for  new   colony   types.   In   addition   one   plate   from   each   replicate   was   randomly   chosen   to   count  the  numbers  of  ancestral  colonies,  the  numbers  of  the  most  common  colony   type,   the   total   numbers   of   new   type   colonies,   numbers   of   switcher   colonies   and   colony   diversity   (number   of   different   colony   morphologies).   As   soon   as   a   new  

Founder( popula,ons( SBW25& 1s1& 1s2& 1s3& 1s4& 1.&&

Transfer& Transfer&2.&& Transfer&3.&&

6(µl(( ((

6(µl((

(( 6(((µl((

.&.&.&&

new/SW( new/SW( new/SW( new/SW(

switcher&stored&at&980°C( & & & un,l(new( type(was( found( (

colony  type  was  found  on  one  of  the  four  plates,  the  replicate  line  was  terminated   (Fig.  5.2).    

Colonies   that   showed   switching   characteristics   were   transferred   to   new   KB   agar   plates   from   which   a   single   colony   was   used   to   inoculate   an   overnight   culture,   which  was  then  stored  at  -­‐80°C  the  following  day.  In  addition,  the  new  switching  

type   was   transferred   to   new   agar   plates   several   times   in   a   row   to   certify   the   inheritance  of  the  novel  phenotype.  Furthermore,  negative  staining  with  Indian  ink   confirmed   a   switcher   phenotype   on   the   cellular   level   under   the   microscope   (see   Chapter  1,  Fig.  1.9C).  Where  no  new  type  was  observed  on  the  plates,  6  µl  of  the  

three-­‐day   culture   were   transferred   to   a   fresh   microcosm,   which   was   left   undisturbed   for   another   three   days   under   the   same   environmental   conditions   (first   transfer).   This   procedure   was   repeated   parallel   to   diluting,   plating   and   screening  until  a  new  type  was  found  (several  transfers;  Fig.  5.2).    

   

5.2.2 Screening  the  carB  gene  of  re-­‐evolved  switchers    

The  switcher  genotypes  that  evolved  during  the  course  of  the  SREE  were  further   analysed   and   screened   for   an   underlying   mutation   in   the  carB   gene.   A   PCR   was   performed  with  the  primer  pair  SN039  PF  and  SN040  PR,  using  the  protocol  that   was   described   earlier   (see   Chapter   2,   section  2.2.1.1).   The   PCR   products   were   sequenced  using  carB  specific  primers  (SN009  PF,  SN010  PF,  SN013  PF,  SN014  PF,   SN015  PF,  SN016  PF,  SN017  PF,  SN018  PF  and  SN070  PR;  see  Chapter  2,  Tab.  2.3)   and  screened  for  changes  in  the  DNA  sequence  by  comparison  to  the  P.  fluorescens   SBW25  ancestral  DNA  sequence  using  the  alignment  software  Sequencher.  

   

5.2.3 Statistical  analyses    

The   software   JMP   9.0   was   used   to   perform   generalised   linear   models   using   the   data  obtained  during  the  SREE.  The  data  included  number  of  switcher  that  were  

detected  on  plates  after  the  dilution  of  a  population  containing  109  cells  as  well  as  

number  of  new  colony  types  and  number  of  ancestors.  Illustrations  of  the  results   were  created  with  the  software  Prism  5.  

   

5.3

Results  

 

5.3.1 The  re-­‐evolution  of  switching  genotypes  in  SBW25,  1s1,  1s2,  1s3   and  1s4  (SREE)  

 

5.3.1.1 Total  number  of  re-­‐evolved  switcher  genotypes    

The  founder  lineages  SBW25,  1s1,  1s2,  1s3  and  1s4  evolved  in  Line  1  during  the   course   of   the   REE   at   different   evolutionary   time   points   (see   Chapter   1,   section   1.4.4).  The  evolution  of  a  switcher  genotype  from  1s4  in  a  static  environment  was   already   observed   during   the   course   of   the   REE   (Beaumont  et   al.,   2009,   Gallie,   2009).   In   this   study   I   was   interested   in   the   likelihood   of   switcher   occurrence   at   earlier  time  points  represented  by  the  original  common  ancestor  SBW25  and  the   genotypes  1s1,  1s2  and  1s3  in  addition  to  the  immediate  ancestor  of  the  switcher,   1s4.  The  average  number  in  60  replicate  microcosms  in  three  experimental  blocks   (N   =   3)   that   produced   a   switcher   genotype   was   then   calculated.   The   results   of   a   generalised   linear   model   show   that   the   different   genotypes   vary   in   their   probability   to   produce   switcher   genotypes   (X26   =   17.96,  P  <   0.01).   Most   of   the  

difference   was   explained   by   the   lineage   itself   (X24   =   43.16,   P   <   0.0001).   The  

genotypes   1s3   and   1s4   had   the   highest   number   of   microcosms   that   produced   a   switcher  (Fig.  5.3)  and  showed  a  similar  likelihood  of  switcher  occurrence  (X24  =  

2.9   10-­‐31,  P   =   1).   Both   were   distinctive   from   the   other   lineages   in   their   ability   to  

produce  switchers  (X24  =  16.47,  P  <  0.0001).  No  switcher  was  detected  in  1s1  (Fig.  

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