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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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Linker sequence is depleted for translationally optimal codons.The frequency of optimal codons (FOP) as a function of the natural logarithm of protein abundance and nucleosome occupancy across gene cores considering all degenerate amino acids.
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pgen-1000250-g005: Linker sequence is depleted for translationally optimal codons.The frequency of optimal codons (FOP) as a function of the natural logarithm of protein abundance and nucleosome occupancy across gene cores considering all degenerate amino acids.

Mentions: Third, these results have an important implication for interpreting local patterns of codon usage. Translationally optimal codons are frequently depleted from linker regions (Table 2). As a result, adaptation for translational efficiency is reduced in linker sequence, as evidenced by a reduced frequency of optimal codons (FOP) (Figure 5; paired t-test for extended core regions: ΔFOP(well-positioned-linker) = 11.20, P<2.2E-16; ΔFOP(fuzzy-linker) = 11.73, P<2.2E-16; ΔFOP(well-positioned-fuzzy) = −3.7, P = 3E-04) and longer runs of translationally non-optimal codons are more likely (Table S6). Previously, runs of non-optimal codons have been considered in the context of selection on translation regulation [56]. Such runs may, for example, induce ribosomal stalling as non-optimal codons tend to be specified by rare tRNAs. This in turn may affect protein folding [57]–[59]. Specification of linker sequence provides a viable alternative hypothesis for a subset of these runs (Table S6).


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

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

Linker sequence is depleted for translationally optimal codons.The frequency of optimal codons (FOP) as a function of the natural logarithm of protein abundance and nucleosome occupancy across gene cores considering all degenerate amino acids.
© Copyright Policy
Related In: Results  -  Collection

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

pgen-1000250-g005: Linker sequence is depleted for translationally optimal codons.The frequency of optimal codons (FOP) as a function of the natural logarithm of protein abundance and nucleosome occupancy across gene cores considering all degenerate amino acids.
Mentions: Third, these results have an important implication for interpreting local patterns of codon usage. Translationally optimal codons are frequently depleted from linker regions (Table 2). As a result, adaptation for translational efficiency is reduced in linker sequence, as evidenced by a reduced frequency of optimal codons (FOP) (Figure 5; paired t-test for extended core regions: ΔFOP(well-positioned-linker) = 11.20, P<2.2E-16; ΔFOP(fuzzy-linker) = 11.73, P<2.2E-16; ΔFOP(well-positioned-fuzzy) = −3.7, P = 3E-04) and longer runs of translationally non-optimal codons are more likely (Table S6). Previously, runs of non-optimal codons have been considered in the context of selection on translation regulation [56]. Such runs may, for example, induce ribosomal stalling as non-optimal codons tend to be specified by rare tRNAs. This in turn may affect protein folding [57]–[59]. Specification of linker sequence provides a viable alternative hypothesis for a subset of these runs (Table S6).

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.

Show MeSH
Related in: MedlinePlus