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The impact of the nucleosome code on protein-coding sequence evolution in yeast.

Warnecke T, Batada NN, Hurst LD - PLoS Genet. (2008)

Bottom Line: A reduced rate of evolution in linker is especially evident at the 5' end of genes, where the effect extends to non-synonymous substitution rates.We conclude that selection operating on DNA to maintain correct positioning of nucleosomes impacts codon choice, amino acid choice, and synonymous and non-synonymous rates of evolution in coding sequence.The results support the exclusion model for nucleosome positioning and provide an alternative interpretation for runs of rare codons.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.

ABSTRACT
Coding sequence evolution was once thought to be the result of selection on optimal protein function alone. Selection can, however, also act at the RNA level, for example, to facilitate rapid translation or ensure correct splicing. Here, we ask whether the way DNA works also imposes constraints on coding sequence evolution. We identify nucleosome positioning as a likely candidate to set up such a DNA-level selective regime and use high-resolution microarray data in yeast to compare the evolution of coding sequence bound to or free from nucleosomes. Controlling for gene expression and intra-gene location, we find a nucleosome-free "linker" sequence to evolve on average 5-6% slower at synonymous sites. A reduced rate of evolution in linker is especially evident at the 5' end of genes, where the effect extends to non-synonymous substitution rates. This is consistent with regular nucleosome architecture in this region being important in the context of gene expression control. As predicted, codons likely to generate a sequence unfavourable to nucleosome formation are enriched in linker sequence. Amino acid content is likewise skewed as a function of nucleosome occupancy. We conclude that selection operating on DNA to maintain correct positioning of nucleosomes impacts codon choice, amino acid choice, and synonymous and non-synonymous rates of evolution in coding sequence. The results support the exclusion model for nucleosome positioning and provide an alternative interpretation for runs of rare codons. As the intimate association of histones and DNA is a universal characteristic of genic sequence in eukaryotes, selection on coding sequence composition imposed by nucleosome positioning should be phylogenetically widespread.

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Nucleosome-free regions show a divergent pattern of amino acid usage.Amino acid usage by occupancy state in concatenated CDS cores are shown. Each data point represents an expression bin (see main text). Long and short horizontal bars represent the proportional usage (out of 1000) of the respective amino acid across all amino acids in the current sample and the genome, respectively, regardless of occupancy state. Significant depletion/enrichment relative to the proportional usage across occupancy states in the sample is indicated by an asterisk (Wilcoxon test; significance threshold adjusted to account for multiple testing across occupancy states (3) and amino acids (20), P<8.3E-04). See Table S3 for P values for all regions and amino acids.
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pgen-1000250-g003: Nucleosome-free regions show a divergent pattern of amino acid usage.Amino acid usage by occupancy state in concatenated CDS cores are shown. Each data point represents an expression bin (see main text). Long and short horizontal bars represent the proportional usage (out of 1000) of the respective amino acid across all amino acids in the current sample and the genome, respectively, regardless of occupancy state. Significant depletion/enrichment relative to the proportional usage across occupancy states in the sample is indicated by an asterisk (Wilcoxon test; significance threshold adjusted to account for multiple testing across occupancy states (3) and amino acids (20), P<8.3E-04). See Table S3 for P values for all regions and amino acids.

Mentions: If nucleosome positioning is responsible for elevated linker conservation then we might additionally expect to see skews in patterns of codon and amino acid usage. We compared codon and amino acid composition between OSs within the S. cerevisiae genome. As alignability is not an issue in this analysis, we can exploit a substantially larger number of genes ≥906 nt (N = 1986). Figure 3 shows for core sequence binned by protein abundance that multiple amino acids are depleted or enriched in linker sequence relative to their proportional use across all core sequence (regardless of OS).


The impact of the nucleosome code on protein-coding sequence evolution in yeast.

Warnecke T, Batada NN, Hurst LD - PLoS Genet. (2008)

Nucleosome-free regions show a divergent pattern of amino acid usage.Amino acid usage by occupancy state in concatenated CDS cores are shown. Each data point represents an expression bin (see main text). Long and short horizontal bars represent the proportional usage (out of 1000) of the respective amino acid across all amino acids in the current sample and the genome, respectively, regardless of occupancy state. Significant depletion/enrichment relative to the proportional usage across occupancy states in the sample is indicated by an asterisk (Wilcoxon test; significance threshold adjusted to account for multiple testing across occupancy states (3) and amino acids (20), P<8.3E-04). See Table S3 for P values for all regions and amino acids.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2570795&req=5

pgen-1000250-g003: Nucleosome-free regions show a divergent pattern of amino acid usage.Amino acid usage by occupancy state in concatenated CDS cores are shown. Each data point represents an expression bin (see main text). Long and short horizontal bars represent the proportional usage (out of 1000) of the respective amino acid across all amino acids in the current sample and the genome, respectively, regardless of occupancy state. Significant depletion/enrichment relative to the proportional usage across occupancy states in the sample is indicated by an asterisk (Wilcoxon test; significance threshold adjusted to account for multiple testing across occupancy states (3) and amino acids (20), P<8.3E-04). See Table S3 for P values for all regions and amino acids.
Mentions: If nucleosome positioning is responsible for elevated linker conservation then we might additionally expect to see skews in patterns of codon and amino acid usage. We compared codon and amino acid composition between OSs within the S. cerevisiae genome. As alignability is not an issue in this analysis, we can exploit a substantially larger number of genes ≥906 nt (N = 1986). Figure 3 shows for core sequence binned by protein abundance that multiple amino acids are depleted or enriched in linker sequence relative to their proportional use across all core sequence (regardless of OS).

Bottom Line: A reduced rate of evolution in linker is especially evident at the 5' end of genes, where the effect extends to non-synonymous substitution rates.We conclude that selection operating on DNA to maintain correct positioning of nucleosomes impacts codon choice, amino acid choice, and synonymous and non-synonymous rates of evolution in coding sequence.The results support the exclusion model for nucleosome positioning and provide an alternative interpretation for runs of rare codons.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.

ABSTRACT
Coding sequence evolution was once thought to be the result of selection on optimal protein function alone. Selection can, however, also act at the RNA level, for example, to facilitate rapid translation or ensure correct splicing. Here, we ask whether the way DNA works also imposes constraints on coding sequence evolution. We identify nucleosome positioning as a likely candidate to set up such a DNA-level selective regime and use high-resolution microarray data in yeast to compare the evolution of coding sequence bound to or free from nucleosomes. Controlling for gene expression and intra-gene location, we find a nucleosome-free "linker" sequence to evolve on average 5-6% slower at synonymous sites. A reduced rate of evolution in linker is especially evident at the 5' end of genes, where the effect extends to non-synonymous substitution rates. This is consistent with regular nucleosome architecture in this region being important in the context of gene expression control. As predicted, codons likely to generate a sequence unfavourable to nucleosome formation are enriched in linker sequence. Amino acid content is likewise skewed as a function of nucleosome occupancy. We conclude that selection operating on DNA to maintain correct positioning of nucleosomes impacts codon choice, amino acid choice, and synonymous and non-synonymous rates of evolution in coding sequence. The results support the exclusion model for nucleosome positioning and provide an alternative interpretation for runs of rare codons. As the intimate association of histones and DNA is a universal characteristic of genic sequence in eukaryotes, selection on coding sequence composition imposed by nucleosome positioning should be phylogenetically widespread.

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