Diversity in G+C content at the third position of codons in vertebrate genes and its cause

Aota, Shin-ichi; Ikemura, Toshimichi

doi:10.1093/nar/14.16.6345

Cited by 193 publications

(92 citation statements)

References 24 publications

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“…This isochore structure, as it is termed (13), is thought to be due to regional differences in mutation bias (14,15). The observation is that genes in AϩT-rich isochores tend to have AϩT predominantly at silent sites, while genes in GϩC-rich isochores have GϩC more often at silent sites (16,17). This is shown by a correlation between base content of introns and the exons of the same gene.…”

Section: Causesmentioning

confidence: 99%

Evolution of codon usage bias in Drosophila

Powell

Moriyama

1997

Proc. Natl. Acad. Sci. U.S.A.

293

196

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We first review what is known about patterns of codon usage bias in Drosophila and make the following points: (i) Drosophila genes are as biased or more biased than those in microorganisms. (vii) Finally, smaller genes tend to be more biased than longer genes. We then examine possible causes of these patterns and discount mutation bias on three bases: there is little evidence of regional mutation bias in Drosophila, mutation bias is likely toward A؉T (the opposite of codon usage bias), and not all amino acids display the preference for the same nucleotide in the wobble position. Two lines of evidence support a selection hypothesis based on tRNA pools: highly biased genes tend to be highly and͞or rapidly expressed, and the preferred codons in highly biased genes optimally bind the most abundant isoaccepting tRNAs. Finally, we examine the effect of bias on DNA evolution and confirm that genes with high codon usage bias have lower rates of synonymous substitution between species than do genes with low codon usage bias. Surprisingly, we find that genes with higher codon usage bias display higher levels of intraspecific synonymous polymorphism. This may be due to opposing effects of recombination.As far as is known, synonymous mutations are truly neutral with respect to natural selection.The above quotation from King and Jukes (1) was one of the major, and more reasonable, tenets of the neutral theory of molecular evolution. With few exceptions (e.g., ref.2), even those researchers who tended toward the selectionist view of molecular evolution were willing to concede synonymous substitutions to the neutralists. After all, such mutations do not affect the structure of the primary gene product and therefore should not be able to affect the phenotype, the level at which natural selection acts. One of the more surprising observations provided by the accumulating DNA sequence data has been the evidence that selection can and does affect synonymous substitutions.

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Section: Causesmentioning

confidence: 99%

Evolution of codon usage bias in Drosophila

Powell

Moriyama

1997

Proc. Natl. Acad. Sci. U.S.A.

293

196

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“…It has been shown recently (4), that the nuclear genome of warm-blooded vertebrates exhibits a compositional compartmentalization, being a mosaic of very long DNA sequences which are relatively homogeneous in their G+C-content (either G+C-rich or A+T-rich). These segments are named 'isochores', and it has been proposed that genes that map in chromosomal R-bands belong to G+C-rich isochores, and those in G-bands to A+T-rich isochores (4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, a high correlation is found between the G + Ccontent at the third codon position of exons and the neighboring introns and flanking sequences. These relationships indicate the existence of compositional constraints operating on both coding and noncoding sequences (5)(6)(7)9,10).…”

Section: Introductionmentioning

confidence: 99%

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Variation in G+C-content and codon choice: differences among synonymous codon groups in vertebrate genes

Marı́n¹,

Bertranpetit

Oliver

et al. 1989

Nucl Acids Res

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The relationship between G+C-content and codon usage in genes of human, mus, rat, bovine and chicken nuclear genomes was investigated. Correlation and lineal regression analyses were carried out on plots that related the frequency of each codon within each synonymous codon group to the G+C-content of the coding sequence as a whole. Under GC pressure, in most of the quartet codon groups there is a preferential choice of the C-ending codon, except in leucine and valine codon groups where the choice of the G-ending codon is preferred. Among duets, the choice of codons specifying phenylalanine and glutamate shows the strongest dependence on G+C-content. The relationship found between G+C-content and codon usage in these genomes correlate with taxonomic distance. INTRODUCTIONEarly works showed that the base ratio A+T/G+C of overall DNA differs among different species (1), and that different DNA segments isolated from organisms of a given species have the same base ratio (2,3).However, in vertebrates there are large differences in base composition between different DNA regions in the same genome. It has been shown recently (4), that the nuclear genome of warm-blooded vertebrates exhibits a compositional compartmentalization, being a mosaic of very long DNA sequences which are relatively homogeneous in their G+C-content (either G+C-rich or A+T-rich). These segments are named 'isochores', and it has been proposed that genes that map in chromosomal R-bands belong to G+C-rich isochores, and those in G-bands to A+T-rich isochores (4-8).According to the degeneracy of the genetic code one might expect that differences in G+C-content among genes could be accounted for by changes in G+C-content at the third, and to a lesser extent, at the first codon position, while the second codon position is constrained by the choice of amino acid. The G+C level found at each codon position in vertebrate genes shows a positive linear relationship to the G+C-content of the corresponding coding sequences; the slopes of the regression lines increase from second, to first, to third positions. Furthermore, a high correlation is found between the G + Ccontent at the third codon position of exons and the neighboring introns and flanking sequences. These relationships indicate the existence of compositional constraints operating on both coding and noncoding sequences (5-7,9,10).The variation in G + C-content through the genome is accompanied by changes in codon usage (4-7). In vertebrate genes, the G+C-content at the third codon position is distributed over a wide range (7), and subsequently, the codon-choice patterns of various genes in the same organism may differ considerably.

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“…There is a strong preference for codons containing a maximal number of G+C. The usage of G+C at the third position of codons is one of the highest (96%) found in vertebrate genes (29).…”

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confidence: 99%

Isolation and sequence of complementary DNA encoding human extracellular superoxide dismutase.

Hjalmarsson¹,

Marklund²,

Engström³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

225

162

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A complementary DNA (cDNA) clone from a human placenta cDNA library encoding extracellular superoxide dismutase (EC-SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) has been isolated and the nucleotide sequence determined. The cDNA has a very high G+C content. EC-SOD is synthesized with a putative 18-amino acid signal peptide, preceding the 222 amino acids in the mature enzyme, indicating that the enzyme is a secretory protein. The first 95 amino acids of the mature enzyme show no sequence homology with other sequenced proteins and there is one possible N-glycosylation site (Asn-89). The amino acid sequence from residues 96-193 shows strong homology (:50%) with the rinal two-thirds of the sequences of all known eukaryotic CuZn SODs, whereas the homology with the P. leiognathi CuZn SOD is clearly lower. The ligands to Cu and Zn, the cysteines forming the intrasubunit disulfide bridge in the CuZn SODs, and the arginine found in all CuZn SODs in the entrance to the active site can all be identified in EC-SOD. A comparison with bovine CuZn SOD, the three-dimensional structure of which is known, reveals that the homologies occur in the active site and the divergencies are in the part constituting the subunit contact area in CuZn SOD. Amino acid sequence 194-222 in the carboxyl-terminal end of EC-SOD is strongly hydrophilic and contains nine amino acids with a positive charge. This sequence probably confers the affnity of EC-SOD for heparin and heparan sulfate.

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Diversity in G+C content at the third position of codons in vertebrate genes and its cause

Cited by 193 publications

References 24 publications

Evolution of codon usage bias in Drosophila

Evolution of codon usage bias in Drosophila

Variation in G+C-content and codon choice: differences among synonymous codon groups in vertebrate genes

Isolation and sequence of complementary DNA encoding human extracellular superoxide dismutase.

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