Limits...
CYNTENATOR: progressive gene order alignment of 17 vertebrate genomes.

Rödelsperger C, Dieterich C - PLoS ONE (2010)

Bottom Line: Gene order conservation or conserved synteny was seen as a feature of common descent and did not imply the existence of functional constraints.We even see significant gene ontology term enrichments for breakpoint regions of ancestral nodes close to the root of the phylogeny.Additionally, our analysis of transposable elements has revealed a significant accumulation of LINE-1 elements in mammalian breakpoint regions.

View Article: PubMed Central - PubMed

Affiliation: Institute for Medical Genetics, Charité-Universitätsmedizin, Berlin, Germany.

ABSTRACT
Whole genome gene order evolution in higher eukaryotes was initially considered as a random process. Gene order conservation or conserved synteny was seen as a feature of common descent and did not imply the existence of functional constraints. This view had to be revised in the light of results from sequencing dozens of vertebrate genomes.It became apparent that other factors exist that constrain gene order in some genomic regions over long evolutionary time periods. Outside of these regions, genomes diverge more rapidly in terms of gene content and order.We have developed CYNTENATOR, a progressive gene order alignment software, to identify genomic regions of conserved synteny over a large set of diverging species. CYNTENATOR does not depend on nucleotide-level alignments and a priori homology assignment. Our software implements an improved scoring function that utilizes the underlying phylogeny.In this manuscript, we report on our progressive gene order alignment approach, a and give a comparison to previous software and an analysis of 17 vertebrate genomes for conservation in gene order.CYNTENATOR has a runtime complexity of and a space complexity of with being the gene number in a genome. CYNTENATOR performs as good as state-of-the-art software on simulated pairwise gene order comparisons, but is the only algorithm that works in practice for aligning dozens of vertebrate-sized gene orders.Lineage-specific characterization of gene order across 17 vertebrate genomes revealed mechanisms for maintaining conserved synteny such as enhancers and coregulation by bidirectional promoters. Genes outside conserved synteny blocks show enrichments for genes involved in responses to external stimuli, stimuli such as immunity and olfactory response in primate genome comparisons. We even see significant gene ontology term enrichments for breakpoint regions of ancestral nodes close to the root of the phylogeny. Additionally, our analysis of transposable elements has revealed a significant accumulation of LINE-1 elements in mammalian breakpoint regions. In summary, CYNTENATOR is a flexible and scalable tool for the identification of conserved gene orders across multiple species over long evolutionary distances.

Show MeSH
Phlyogenetic tree of 17 vertebrates.Dendroscope view on a subtree of the 28-way MULTIZ alignment tree [24], [38] which we used as a guide tree for the progressive alignment, carried out by CYNTENATOR. Distances at branches indicate the average number of substitutions per site in blastz alignments [39]. These distances were used to weight the scores between gene matches in the alignment.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2812507&req=5

pone-0008861-g001: Phlyogenetic tree of 17 vertebrates.Dendroscope view on a subtree of the 28-way MULTIZ alignment tree [24], [38] which we used as a guide tree for the progressive alignment, carried out by CYNTENATOR. Distances at branches indicate the average number of substitutions per site in blastz alignments [39]. These distances were used to weight the scores between gene matches in the alignment.

Mentions: A match between two genes is computed from the pairwise bitscores of BLAST similarities [22] and the distances in a species tree for and (Figure 1).(1)Mismatch, linear gap, and minimal alignment score threshold are adjusted at each step by multiplying with whereby denotes the phylogenetic distance between both species. The factor of is a reminiscent of SYNTENATOR and is meant to adapt the matchscores of both programs to a comparable level.


CYNTENATOR: progressive gene order alignment of 17 vertebrate genomes.

Rödelsperger C, Dieterich C - PLoS ONE (2010)

Phlyogenetic tree of 17 vertebrates.Dendroscope view on a subtree of the 28-way MULTIZ alignment tree [24], [38] which we used as a guide tree for the progressive alignment, carried out by CYNTENATOR. Distances at branches indicate the average number of substitutions per site in blastz alignments [39]. These distances were used to weight the scores between gene matches in the alignment.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2812507&req=5

pone-0008861-g001: Phlyogenetic tree of 17 vertebrates.Dendroscope view on a subtree of the 28-way MULTIZ alignment tree [24], [38] which we used as a guide tree for the progressive alignment, carried out by CYNTENATOR. Distances at branches indicate the average number of substitutions per site in blastz alignments [39]. These distances were used to weight the scores between gene matches in the alignment.
Mentions: A match between two genes is computed from the pairwise bitscores of BLAST similarities [22] and the distances in a species tree for and (Figure 1).(1)Mismatch, linear gap, and minimal alignment score threshold are adjusted at each step by multiplying with whereby denotes the phylogenetic distance between both species. The factor of is a reminiscent of SYNTENATOR and is meant to adapt the matchscores of both programs to a comparable level.

Bottom Line: Gene order conservation or conserved synteny was seen as a feature of common descent and did not imply the existence of functional constraints.We even see significant gene ontology term enrichments for breakpoint regions of ancestral nodes close to the root of the phylogeny.Additionally, our analysis of transposable elements has revealed a significant accumulation of LINE-1 elements in mammalian breakpoint regions.

View Article: PubMed Central - PubMed

Affiliation: Institute for Medical Genetics, Charité-Universitätsmedizin, Berlin, Germany.

ABSTRACT
Whole genome gene order evolution in higher eukaryotes was initially considered as a random process. Gene order conservation or conserved synteny was seen as a feature of common descent and did not imply the existence of functional constraints. This view had to be revised in the light of results from sequencing dozens of vertebrate genomes.It became apparent that other factors exist that constrain gene order in some genomic regions over long evolutionary time periods. Outside of these regions, genomes diverge more rapidly in terms of gene content and order.We have developed CYNTENATOR, a progressive gene order alignment software, to identify genomic regions of conserved synteny over a large set of diverging species. CYNTENATOR does not depend on nucleotide-level alignments and a priori homology assignment. Our software implements an improved scoring function that utilizes the underlying phylogeny.In this manuscript, we report on our progressive gene order alignment approach, a and give a comparison to previous software and an analysis of 17 vertebrate genomes for conservation in gene order.CYNTENATOR has a runtime complexity of and a space complexity of with being the gene number in a genome. CYNTENATOR performs as good as state-of-the-art software on simulated pairwise gene order comparisons, but is the only algorithm that works in practice for aligning dozens of vertebrate-sized gene orders.Lineage-specific characterization of gene order across 17 vertebrate genomes revealed mechanisms for maintaining conserved synteny such as enhancers and coregulation by bidirectional promoters. Genes outside conserved synteny blocks show enrichments for genes involved in responses to external stimuli, stimuli such as immunity and olfactory response in primate genome comparisons. We even see significant gene ontology term enrichments for breakpoint regions of ancestral nodes close to the root of the phylogeny. Additionally, our analysis of transposable elements has revealed a significant accumulation of LINE-1 elements in mammalian breakpoint regions. In summary, CYNTENATOR is a flexible and scalable tool for the identification of conserved gene orders across multiple species over long evolutionary distances.

Show MeSH