How neutral are synonymous codon mutations?

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How do synonymous mutations affect fitness?

While it has often been assumed that, in humans, synonymous mutations would have no effect on fitness, let alone cause disease, this position has been questioned over the last decade. There is now considerable evidence that such mutations can, for example, disrupt splicing and interfere with miRNA binding. Two recent publications suggest involvement of additional mechanisms: modification of pro...

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Synonymous Codon Substitution Matrices

Observing differences between DNA or protein sequences and estimating the true amount of substitutions from them is a prominent problem in molecular evolution as many analyses are based on distance measures between biological sequences. Since the relationship between the observed and the actual amount of mutations is very complex, more than four decades of research have been spent to improve mo...

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Synonymous mutations in CFTR exon 12 affect splicing and are not neutral in evolution.

It is well established that exonic sequences contain regulatory elements of splicing that overlap with coding capacity. However, the conflict between ensuring splicing efficiency and preserving the coding capacity for an optimal protein during evolution has not been specifically analyzed. In fact, studies on genomic variability in fields as diverse as clinical genetics and molecular evolution m...

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Synonymous codon usage in bacteria.

In most bacteria, synonymous codons are not used with equal frequencies. Different factors have been proposed to contribute to codon usage preference, including translational selection, GC composition, strand-specific mutational bias, amino acid conservation, protein hydropathy, transcriptional selection and even RNA stability. The review discusses these factors and their contribution to bias i...

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Synonymous Codon Usage Controls Various Molecular Aspects

Synonymous sites are generally considered to be functionally neutral. However, there are recent contradictory findings suggesting that synonymous alleles might have functional roles in various molecular aspects. For instance, a recent study demonstrated that synonymous single nucleotide polymorphisms have a similar effect size as nonsynonymous single nucleotide polymorphisms in human disease as...

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ژورنال

عنوان ژورنال: Nature Genetics

سال: 1995

ISSN: 1061-4036,1546-1718

DOI: 10.1038/ng0795-259