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Capítulo 3. Aplicación del procedimiento para contribuir a mejorar el desempeño de la cadena de

3.1. Caracterización general de la cadena y establecimiento del equipo de trabajo

ECOLOGICAL  CONTEXT  

1.6.1  ARABIDOPSIS  THALIANA:  AN  IDEAL  MODEL  

Though  work  on  our  own  species  has  generally  led  the  field  –  indeed,  many  of   the   concepts   and   methods   to   be   discussed   in   this   report   will   continue   to   cite   work  on  human  populations  that  has,  in  one  way  or  another,  blazed  the  trail  –   most   of   the   knowledge   gained   and   techniques   pioneered   in   human   genetic   research  are  equally  applicable  to  research  in  other  species.  First  amongst  these   other  species  in  plant  genetics  has  been  the  model  plant  Arabidopsis  thaliana,  or   Thale  cress.  This  species  is  favoured  by  plant  scientists  for  its  ease  of  growth,   extensive  wild  range  and  short  generation  time  (Meyerowitz  &  Pruitt  1985),  as   a   model   for   molecular   genetic   investigation   of   plant   development,   host-­‐ pathogen   interactions,   and   increasingly   as   an   organism   for   ecological   investigation   of   natural   populations   .   Along   with   its   extensive   record   of   pre-­‐ existing  genetic  experimentation,  its  small  genome  –  one  of  the  smallest  of  any   flowering  plant  –  made  it  an  attractive  proposition  to  the  scientists  involved  in   the   first   sequencing   projects;   and   so   it   was   one   of   the   first   eukaryotes   ever   sequenced,  before  even  our  own  species.  

Arabidopsis   thaliana   is   a   member   of   the   family   Brassicaceae,   a   large   and  

extremely  diverse  group  that  has  radiated  to  a  staggering  range  of  habitats  and   ecological   niches.   Some   wild   relatives   like  Capsella   bursa-­pastoris  (Shepherds   Purse)   are   invasive   weeds,   whereas   others   have   been   domesticated   as   vegetable  of  oilseed  crops  such  as  Brassica  oleracea  (cabbage,  broccoli,  Brussels   sprouts   and   cauliflower),   B.   napus  (oilseed   rape),  Raphanus   sativus   (radish),  

Brassica  rapa  (turnip),  and  Lepidium  sativum  (cress).  A  better  understanding  of  

the   biology   of  A.   thaliana   inevitably   translates   to   a   better   understanding   of   these  close  relatives  (Bancroft  2000).  

A.   thaliana   is   ideally   suited   for   molecular   genetic   research.   Its   outcrossing  

into   small   near-­‐isogenic,   relatively   rarely   intermingling   groups   known   as   ‘accessions’  (Mitchell-­‐Olds  2001;  Bergelson  et  al.  1998).  Its  wide  native  range,   spanning   much   of   the   Northern   hemisphere   and   a   considerable   range   of   latitudes,  also  makes  it  an  excellent  source  of  knowledge  regarding  adaptation   to   different   climate   types   and   habitats.   Despite   its   propensity   for   self-­‐ fertilisation,   the   wild   population   retains   a   large   amount   of   genetic   variation,   including   variation   at   loci   associated   with   traits   of   significant   agronomic   importance  to  crop  species  within  the  Brassicaceae.  

Additionally,  A.   thaliana   has   proved   a   great   source   of   knowledge   in   terms   of   genomics.  The  genes  controlling  the  plant’s  development  have  been  extensively   mapped   and   studied.   Much   is   known   regarding   the   exact   molecular   mechanisms  A.   thaliana   uses   to   detect   and   respond   to   changes   in   abiotic   conditions   such   as   temperature,   day   length   and   water   availability   in   its   environment.   For   example,   GWAS   experiments   have   revealed   multiple   genes   associated  with  control  of  flowering  time  in  response  to  day  length  (Ehrenreich   et  al.  2009).  

A   good   deal   is   also   known   about   the   molecular   mechanisms   by   which  A.  

thaliana   detects   and   reacts   to   challenges   from   biotic   factors,   including  

parasites;   A.   thaliana  is   known   to   possess   both   broad-­‐spectrum   defensive   measures   effective   against   a   wide   array   of   microbial   species,   such   as   those   controlled  by  the  jasmonic  and  salicylic  acid  defence  pathways  (Kniskern  et  al.   2007),  and  specific  defenses  that  evolved  as  counters  to  the  action  of  proteins   secreted   by   pathogens   in   order   to   suppress   or   evade   those   defences.   Parts   of   this   project   involving   an   attempt   to   identify   instances   of   adaptation   in   A.  

thaliana  will  take  particular  note  of  genes  of  the  latter  type,  since  they  are  likely  

to   be   in   a   constant   evolutionary   arms   race   against   their   opposite   numbers   in   species   which   parasitise  A.   thaliana.   See   Chapter  1.7   for   an   overview   of   our   current   understanding   of   interactions   between   plants   and   pathogens   as   described  by  the  “zigzag  model”  (Dangl  &  Jones  2001;  Jones  &  Dangl  2006),    

Given  this  rare  combination  of  existing  knowledge  and  continued  relevance  to   ongoing   research,   it   was   only   a   matter   of   time   before   the   very   latest   genetic   research  methodology  was  applied  to  A.  thaliana.    

 

1.6.2  FROM  MAN  TO  PLANT:  ONE  MODEL  INFORMING  ANOTHER  

The  International  HapMap  project  provided  an  impetus  for  the  plant  research   community  to  initiate  its  own  A.  thaliana  HapMap  project  in  2005.  This  global   project,   comparable   in   scope   to   its   human-­‐based   equivalent,   utilised   a   high-­‐

throughput   technique   based   on   RNA   microarrays   (Borevitz   et   al.   2003)   to   genotype  A.  thaliana  samples.  The  European  and  UK-­‐wide  distribution  of  sites   at  which  these  accessions  were  sampled  is  shown  in  Figure  4.  These  accessions   were  initially  genotyped  using  a  low  density  set  of  149  SNPs;  these  genotypes   were  then  used  to  select  a  smaller  subset  of  916  accessions,  covering  as  much  of   the  population’s  genetic  diversity  as  possible,  which  were  then  genotyped  at  a   higher   density   of   350,000   SNPs.   Many   of   these   SNPs   were   rejected   due   to   duplication  or  uncertainty,  leaving  a  final  dataset  of  genotypic  variation  across   216000  SNP  loci,  known  as  the  250K  dataset  (Kim  et  al.  2007).    

One   of   the   first   analyses   completed   from   this   dataset   was   a   map   of   linkage   disequilibrium  across  the  Arabidopsis  genome.  Despite  the  low  outcrossing  rate   of  the  species,  Kim  et  al.  (2007)  found  that  linkage  disequilibrium  between  loci   breaks  down  when  loci  are  separated  by,  on  average,  10kb.    

1.6.3  A.  THALIANA  AS  A  MEANS  OF  REVEALING  ECOLOGICALLY  IMPORTANT   VARIATION  

As   with   human   genomics,   genome-­‐wide   association   studies   have   been   performed   for   many   ecologically   and   agronomically   significant   traits   in   A.  

thaliana.   A   prominent   example   is   that   of   flowering   time.   Since   A.   thaliana  

inhabits   such   a   surprisingly   vast   range   of   latitudes   –   from   Scandinavia   to   the   sub-­‐tropics  –  it  must  be  able  to  adapt  to  a  wide  variety  of  climatic  temperature   ranges  and  day  lengths.  In  fact,  A.  thaliana  is  known  to  have  developed  different   strategies   for   the   combinations   of   these   and   other   climatic   variables   it   faces   across  its  latitude  range,  and  control  of  flowering  time  is  known  to  play  a  key   role   in   this   adaptation   (Michaels   et   al.   2003).   Across   most   of   its   range,  A.  

thaliana  typically  lives  as  a  winter  annual,  producing  a  single  generation  each  

year.   Growth   begins   with   autumnal   germination   and   continues   the   winter,   terminating  with  flowering  and  seeding  in  the  spring  and  seed  dormancy  over   the   summer.   Towards   the   more   northerly   and   colder   extremes   of   its   range,   however,   A.   thaliana   possesses   alleles   associated   with   a   summer   annual   lifecycle  (Michaels  et  al.  2003;  Alonso-­‐Blanco  &  Koornneef  2000).  The  genetic  

basis   of   this   alternative   life   cycle   is   known   to   involve   variation   in   genes   that   control  vernalisation  and  flowering  time,  as  described  by  Michaels  et  al.  (2003)   Consequently,  genes  associated  with  this  trait,  and  other  genes  associated  with   flowering  time,  are  likely  candidates  for  local  adaptation.  Analyses  described  in   this   project   therefore   sought   signatures   of   selection   acting   upon   these   genes   (see  Chapter  4.3.3).    

1.7  HOST-­‐PARASITE  INTERACTIONS  AS  A  MODEL  FOR