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The evolution of transcription-associated biases of mutations across vertebrates.

Polak P, Querfurth R, Arndt PF - BMC Evol. Biol. (2010)

Bottom Line: In contrast to all other species analyzed, we found a mutational pressure in dog and stickleback, promoting an increase of GC-contents in the proximity to transcriptional start sites.We propose that the asymmetric patterns in transcribed regions are results of transcription associated mutagenic processes and transcription coupled repair, which both seem to evolve in a taxon related manner.Since dog and stickleback are known to be subject to rapid adaptations due to population bottlenecks and breeding, we further hypothesize that an increase in recombination rates near gene starts has been part of an adaptive process.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany. polak@molgen.mpg.de

ABSTRACT

Background: The interplay between transcription and mutational processes can lead to particular mutation patterns in transcribed regions of the genome. Transcription introduces several biases in mutational patterns; in particular it invokes strand specific mutations. In order to understand the forces that have shaped transcripts during evolution, one has to study mutation patterns associated with transcription across animals.

Results: Using multiple alignments of related species we estimated the regional single-nucleotide substitution patterns along genes in four vertebrate taxa: primates, rodents, laurasiatheria and bony fishes. Our analysis is focused on intronic and intergenic regions and reveals differences in the patterns of substitution asymmetries between mammals and fishes. In mammals, the levels of asymmetries are stronger for genes starting within CpG islands than in genes lacking this property. In contrast to all other species analyzed, we found a mutational pressure in dog and stickleback, promoting an increase of GC-contents in the proximity to transcriptional start sites.

Conclusions: We propose that the asymmetric patterns in transcribed regions are results of transcription associated mutagenic processes and transcription coupled repair, which both seem to evolve in a taxon related manner. We also discuss alternative mechanisms that can generate strand biases and involves error prone DNA polymerases and reverse transcription. A localized increase of the GC content near the transcription start site is a signature of biased gene conversion (BGC) that occurs during recombination and heteroduplex formation. Since dog and stickleback are known to be subject to rapid adaptations due to population bottlenecks and breeding, we further hypothesize that an increase in recombination rates near gene starts has been part of an adaptive process.

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The weak to strong bias along CGI-genes and their flanks. The frequencies of W→S (thick line), S→W (thin line), the stationary GC content (GC*, thick) and the GC content (thin) are plotted against distance from the 5'end and 3'end of genes and calculated along the non-template strand from pooled 200 bp windows of genes annotated for the reference species in each taxon. Only the results for CGI-genes are presented.
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Figure 2: The weak to strong bias along CGI-genes and their flanks. The frequencies of W→S (thick line), S→W (thin line), the stationary GC content (GC*, thick) and the GC content (thin) are plotted against distance from the 5'end and 3'end of genes and calculated along the non-template strand from pooled 200 bp windows of genes annotated for the reference species in each taxon. Only the results for CGI-genes are presented.

Mentions: Besides strand asymmetries we also investigated the impact of substitution rates on the GC content. All genomes of animals that have been sequenced so far are AT rich [23]. However, the GC content along the genome is heterogeneous [24,25], and the GC content in animals is higher near the TSS of genes than in other regions [26]. In particular, in mammals, the GC content near the TSS is higher by about 50% than on a genome wide level [26]. Several studies on the evolution of the GC content near the TSS debate whether selection has shaped the GC content or mutational mechanisms [13,19,26,27]. To address this, we used the estimated substitution rates in order to calculate the stationary GC content (GC*) along genes (Figure 2 and Additional file 5).


The evolution of transcription-associated biases of mutations across vertebrates.

Polak P, Querfurth R, Arndt PF - BMC Evol. Biol. (2010)

The weak to strong bias along CGI-genes and their flanks. The frequencies of W→S (thick line), S→W (thin line), the stationary GC content (GC*, thick) and the GC content (thin) are plotted against distance from the 5'end and 3'end of genes and calculated along the non-template strand from pooled 200 bp windows of genes annotated for the reference species in each taxon. Only the results for CGI-genes are presented.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2927911&req=5

Figure 2: The weak to strong bias along CGI-genes and their flanks. The frequencies of W→S (thick line), S→W (thin line), the stationary GC content (GC*, thick) and the GC content (thin) are plotted against distance from the 5'end and 3'end of genes and calculated along the non-template strand from pooled 200 bp windows of genes annotated for the reference species in each taxon. Only the results for CGI-genes are presented.
Mentions: Besides strand asymmetries we also investigated the impact of substitution rates on the GC content. All genomes of animals that have been sequenced so far are AT rich [23]. However, the GC content along the genome is heterogeneous [24,25], and the GC content in animals is higher near the TSS of genes than in other regions [26]. In particular, in mammals, the GC content near the TSS is higher by about 50% than on a genome wide level [26]. Several studies on the evolution of the GC content near the TSS debate whether selection has shaped the GC content or mutational mechanisms [13,19,26,27]. To address this, we used the estimated substitution rates in order to calculate the stationary GC content (GC*) along genes (Figure 2 and Additional file 5).

Bottom Line: In contrast to all other species analyzed, we found a mutational pressure in dog and stickleback, promoting an increase of GC-contents in the proximity to transcriptional start sites.We propose that the asymmetric patterns in transcribed regions are results of transcription associated mutagenic processes and transcription coupled repair, which both seem to evolve in a taxon related manner.Since dog and stickleback are known to be subject to rapid adaptations due to population bottlenecks and breeding, we further hypothesize that an increase in recombination rates near gene starts has been part of an adaptive process.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany. polak@molgen.mpg.de

ABSTRACT

Background: The interplay between transcription and mutational processes can lead to particular mutation patterns in transcribed regions of the genome. Transcription introduces several biases in mutational patterns; in particular it invokes strand specific mutations. In order to understand the forces that have shaped transcripts during evolution, one has to study mutation patterns associated with transcription across animals.

Results: Using multiple alignments of related species we estimated the regional single-nucleotide substitution patterns along genes in four vertebrate taxa: primates, rodents, laurasiatheria and bony fishes. Our analysis is focused on intronic and intergenic regions and reveals differences in the patterns of substitution asymmetries between mammals and fishes. In mammals, the levels of asymmetries are stronger for genes starting within CpG islands than in genes lacking this property. In contrast to all other species analyzed, we found a mutational pressure in dog and stickleback, promoting an increase of GC-contents in the proximity to transcriptional start sites.

Conclusions: We propose that the asymmetric patterns in transcribed regions are results of transcription associated mutagenic processes and transcription coupled repair, which both seem to evolve in a taxon related manner. We also discuss alternative mechanisms that can generate strand biases and involves error prone DNA polymerases and reverse transcription. A localized increase of the GC content near the transcription start site is a signature of biased gene conversion (BGC) that occurs during recombination and heteroduplex formation. Since dog and stickleback are known to be subject to rapid adaptations due to population bottlenecks and breeding, we further hypothesize that an increase in recombination rates near gene starts has been part of an adaptive process.

Show MeSH