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trait investigated (Koornneef et al.
2004
). Moreover, assays of metabolite profiles
by large-scale unbiased metabolomics methods have uncovered natural variation at
the level of small molecules, suggesting that they reflect physiological phenotypes
that could be under selection in nature (Keurentjes et al.
2006
). Efforts to accelerate
the discovery of functionally important variants began with a large-scale study in
which some 1,000 fragments across the genomes of 96 accessions of
Arabidopsis
thaliana
gathered from all over the world were compared by dideoxy sequencing
(Rosenberg et al.
2005
). A major conclusion from this work was that there has been
considerable global gene flow, so that most sequence variants are found worldwide,
although genotypes are not entirely random. There is isolation by distance, and even
though population structure (which is a division of the population into distinct
subgroups related by kinship) is relatively moderate, it can easily be a confounding
factor in association studies. From this first set of 96 strains, 20 maximally diverse
strains were chosen for much denser polymorphism discovery using array-based
resequencing (Clark et al.
2007
). This led to the identification of approximately one
single nucleotide polymorphism (SNP) for every 200 base pairs of the genome,
constituting one quarter or so of all SNPs estimated to be present. In addition,
regions that are missing or highly divergent in at least one accession encompass
about a quarter of the reference genome. For this reason it is becoming increasingly
clear that it is inappropriate to think about
genome of a species, even though
this is what the initial sequencing papers stated in their titles just a few years ago
(Weigel and Mott
2009
). The previous emphasis on relatively minor changes
between individuals, such as SNPs, was largely due to the fact that sequence
variation had overwhelmingly been studied by PCR-based methods or hybridisation
to known sequences. It is now known that Arabidopsis accessions can vary in
hundreds of genes. Of particular importance is the observation that some genes
with fundamental effects on life history traits such as flowering are not even
functional in their reference accession, and thus could not have been discovered
on the basis of the first genome sequence alone. Whilst knowledge about the origin
and phenotypic effects of sequence polymorphisms is central to understanding how
species adapt to their natural environment, most studies of genetic variation in
Arabidopsis have probably been motivated by the desire to identify regulatory and
other genes that are not present in the common laboratory accessions (Weigel
2012
). A project begun in 2009 aimed to sequence the genome of 1001 accessions
of
A. thaliana
(Weigel and Mott
2009
), and the task is almost complete now. The
main motivation for the 1001 Genomes project is, however, to enable genome-wide
association studies (GWA) in this species. The seeds from the 1001 accessions are
freely available from the
Arabidopsis
stock centres and each accession can be
grown and phenotyped by scientists from all over the world (Weigel and Mott
2009
). Importantly, because an unlimited supply of genetically identical individuals
will be available for each accession, even subtle phenotypes and ones that are
highly sensitive to the microenvironment, which is often difficult to control, can be
measured with a high degree of confidence. The phenotypes can include morpho-
logical analyses, such as plant stature, growth and flowering; investigations of plant
content, such as metabolites and ions; responses to the abiotic environment, such as
the
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