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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.

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Simulation model of speciation events.We used a naive model for speciation events to create some test sets. In this example, the ancestor genome consists of two chromosomes with genes  and . We copy this genome and apply to each branch a number of independent rearrangements. Knowing the evolutionary history of the two branches we can extract all perfect colinear blocks as regions between breakpoints. According to the mapping of genes, homology data is created and passed to CYNTENATOR together with the gene annotations of the branches (see Methods). The CYNTENATOR alignments can then be compared to the simulated blocks.
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pone-0008861-g002: Simulation model of speciation events.We used a naive model for speciation events to create some test sets. In this example, the ancestor genome consists of two chromosomes with genes and . We copy this genome and apply to each branch a number of independent rearrangements. Knowing the evolutionary history of the two branches we can extract all perfect colinear blocks as regions between breakpoints. According to the mapping of genes, homology data is created and passed to CYNTENATOR together with the gene annotations of the branches (see Methods). The CYNTENATOR alignments can then be compared to the simulated blocks.

Mentions: To evaluate the performance of different software and strategies on detecting conserved syntenic regions, we created a simple synthetic scenario of genome evolution (see Figure 2): 1) We generated a small genome with 1040 genes, which are distributed over chromosomes 2) We evolved this genome twenty times independently by applying rearrangements (inversions, translocations, duplications, and deletions of size of ) on two different copies that model descendents of the ancestral genome. We ruled out the possibility that a single gene is involved in two rearrangement events. 3) We stored information on positions and types of individual rearrangements. Genes that originate from the same common ancestor and diverged by speciation and duplications are part of the same gene family.


CYNTENATOR: progressive gene order alignment of 17 vertebrate genomes.

Rödelsperger C, Dieterich C - PLoS ONE (2010)

Simulation model of speciation events.We used a naive model for speciation events to create some test sets. In this example, the ancestor genome consists of two chromosomes with genes  and . We copy this genome and apply to each branch a number of independent rearrangements. Knowing the evolutionary history of the two branches we can extract all perfect colinear blocks as regions between breakpoints. According to the mapping of genes, homology data is created and passed to CYNTENATOR together with the gene annotations of the branches (see Methods). The CYNTENATOR alignments can then be compared to the simulated blocks.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0008861-g002: Simulation model of speciation events.We used a naive model for speciation events to create some test sets. In this example, the ancestor genome consists of two chromosomes with genes and . We copy this genome and apply to each branch a number of independent rearrangements. Knowing the evolutionary history of the two branches we can extract all perfect colinear blocks as regions between breakpoints. According to the mapping of genes, homology data is created and passed to CYNTENATOR together with the gene annotations of the branches (see Methods). The CYNTENATOR alignments can then be compared to the simulated blocks.
Mentions: To evaluate the performance of different software and strategies on detecting conserved syntenic regions, we created a simple synthetic scenario of genome evolution (see Figure 2): 1) We generated a small genome with 1040 genes, which are distributed over chromosomes 2) We evolved this genome twenty times independently by applying rearrangements (inversions, translocations, duplications, and deletions of size of ) on two different copies that model descendents of the ancestral genome. We ruled out the possibility that a single gene is involved in two rearrangement events. 3) We stored information on positions and types of individual rearrangements. Genes that originate from the same common ancestor and diverged by speciation and duplications are part of the same gene family.

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