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BITS2007 Meeting
BITS2007 Meeting



26-28 April 2007 Napoli, Italy

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DrosOCB: a high resolution map of conserved non coding sequences in Drosophila
 
Motivation
The functional annotation of eukaryotic DNA sequences represents a great challenge
in
post-genomic biological research. A great aid to functional annotation of genome
sequences is
provided by comparative genomics methods which, since a few years, have been extended
also to
non coding DNA regions.
However, comparison of non coding sequences requires new algorithms and strategies to
take into
account the different evolutionary mechanisms affecting regulatory sequences. Here,
we present
an novel large scale alignment strategy which aims at drawing a precise map of
conserved non-coding regions between genomes, even when these regions have undergone
small
scale rearrangement events. Our procedure is optimized to take into account the
great
plasticity
of non coding DNA, such as shuffling and sequence variability of binding sites
within
functional
modules, low scale translocations, inversions and duplications.


Methods
The recent availability of 12 Drosophila species sequencing and annotation offers a
complete and reliable genomic dataset for developing and testing methods for
comparative
genomics of non coding DNA.We used a `gene-centric` approch, in that it starts with a
list of
orthologous genes between two species, and applies a local alignment algorithm to
the
corresponding flanking intergenic regions and intronic regions of these orthologous
pairs.
For each Drosophila species took in exam, we compile a list of orthologous
genes with D. Melanogaster, according to the `12 genomes project` data.
Considering each locus in our list, according to the mentioned genome annotation, we
selected
the whole repeated-masked  sequences containing the transcriptional unit and the
corresponding flanking intergenic regions up to the preceding and the following
gene.In this
way, our selection is not constrained from the syntenic order of the orthologous
genes, which
is relevant when we compare species very distant in the evolutionary tree.
Local pairwise alignments between related sequences was performed using CHAOS, which
is
an heuristic alignment algorithm with some peculiar features optimized for large non
coding DNA
sequences. CHAOS works chaining small words  which match between the two
input sequences. Differently from BLAST, it is a double seed technique and it allows
some
degeneracy in seeds. It chains toghether seeds that are closer that a maximum
distance
 and it returns the highest scoring chains, according to a standard Needleman-Wunsch
metric. Hence, it is able to identify conserved blocks rearranged in non-colinear
order or in
a reverse order with a very high resolution. On the other hand, it is able to rapidly
align
large sequences with a better specificity than purely local aligners, thanks to the
double seed
technique.We choose two different sets of parameters in CHAOS and build a
conservative and a
more sensitive version of our alignments.
We applied the described procedure to each list of ortholgous genes between D.
Melanogaster and
seven other Drosophila species, providing a provisional data browser at:
http://139.124.62.227/~carl/UCSC/TrackMaker.php.


Results
We obtained a genome-wide high resolution map of D. Melanogaster compared to other
seven drosophila species.
According to this map, we can extimate conservation features of Drosophila genome at
large scale: the percentage
of conservation of intronic and intergenic genome, the rate of low scale
rearrangement events, as inversions and
reshuffling. Interestingly, we observe numerous small scale rearrangement events,
such as local inversions,
duplications and translocations, which are not observable in the whole genome
alignments currently
available. For example, about 15% of the conserved blocks have been obtained aligning
the
orthologous regions on opposite strands, indicating small scale inversions. Moreover,
because we
allow 1-n relationships between blocks in both aligned species, we immediately spot
duplication
events, like the duplication of the tRNA gene K5:84ABd of D.melanogaster in D.
pseudoobscura.
This catalog of non-coding conserved blocks will constitute the starting point for
several
investigations, related to the evolution of conserved non-coding regions in the
drosophila or the
discovery of cis-regulatory regions.
 
Id: 194
Place: Napoli, Italy
Centro Congressi "Federico II"
Via Partenope 36
Napoli
Starting date:
-- not yet scheduled --   
Duration: 01h00'
Contribution type: Poster
Primary Authors: MARTIGNETTI, Loredana (Department of Theoretical Physics, University of Torino)
Co-Authors: BERNARD, Jacq (Institut de Biologie du De``veloppement de Marseille-Luminy)
CARL, Herrmann (Institut de Biologie du De``veloppement de Marseille-Luminy)
MICHELE, Caselle (Department of Theoretical Physics, University of Torino)
Presenters: MARTIGNETTI, Loredana
 
Included in session: Poster Session
Included in track: Gene expression and system biology
 




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