Synonymous substitution


Synonymous substitution

A synonymous substitution (also called a "silent" substitution) is the evolutionary substitution of one base for another in an exon of a gene coding for a protein, such that the amino acid sequence produced is not modified.

Redundancy in DNA

Protein translation involves a set of twenty amino acids. Each of these amino acids is coded for by a sequence of three DNA base pairs called a "codon". Because there are 64 possible codons, but only 20 amino acids (as well as a stop signal, indicating that translation should stop), some amino acids are coded for by 2, 3, 4, or 6 different codons. For example, the codons TTT and TTC both code for the amino acid phenylalanine. This is often referred to as "redundancy" of the genetic code. There are two mechanisms for redudancy: several different transfer RNAs can deliver the same amino acid, or one tRNA can have a non-standard "wobbly" base in position three of the anti-codon, which recognises more than one base in the codon.

In the above phenylalanine example, suppose that the base in position 3 of a TTT codon got substituted to a C, leaving the codon TTC. The amino acid at that position in the protein will remain a phenylalanine. Hence, the substitution is a synonymous one.

Substitution versus mutation

Although mutation and substitution are often used interchangeably, there is a subtle but important difference. A nucleotide mutation is a base change (whether synonymous or non-synonymous) such that the mutant and wild-type forms coexist in a population. A nucleotide substitution is a base change between two populations. Thus, a mutation only becomes a substitution when the most recent common ancestor of the entire population carried that mutation. When all lineages carrying alternative mutations have died off, the remaining mutation is said to be "fixed". Note that fixed mutations may never reach 100% frequency in the population, as further mutations at the same site may arise; these subsequent mutations, however, will all share a common ancestor which had the fixed mutation.

Synonymous substitutions and evolution

When a synonymous or silent mutation occurs, the change is often assumed to be neutral, meaning that it does not affect the fitness of the individual carrying the new gene to survive and reproduce. Redundancy of the genetic code provides some protection against the effect of mutations.

Synonymous changes may not be neutral because certain codons are translated more efficiently (faster and/or more accurately) than others. For example, when a handful of synonymous changes in the fruit fly alcohol dehydrogenase gene were introduced, changing several codons to sub-optimal synonyms, production of the encoded enzyme was reduced [http://www.genetics.org/cgi/content/abstract/163/1/239] , and the adult flies showed lower ethanol tolerance [http://www.blackwell-synergy.com/doi/pdf/10.1111/j.1420-9101.2004.00725.x] . Many organisms, from bacteria through animals, display biased use of certain synonymous codons. Such codon usage bias may arise for different reasons, some selective, and some neutral.

Substitutions that are not synonymous are often detrimental to the host cell. For instance, a mammalian cell might have a gene coding for a protein that regulates cell division. A mutation that results in a change to the methionine codon that marks the beginning of the gene's open reading frame may cause the gene to become inactivated. The protein that regulates cell division would not be produced, and the cell would grow unchecked, resulting in a tumor cell.

ee also

*Missense mutation
*Point mutation


Wikimedia Foundation. 2010.

Look at other dictionaries:

  • synonymous substitution — synonymous substitution. См. несмысловая замена [нуклеотида]. (Источник: «Англо русский толковый словарь генетических терминов». Арефьев В.А., Лисовенко Л.А., Москва: Изд во ВНИРО, 1995 г.) …   Молекулярная биология и генетика. Толковый словарь.

  • Substitution model — A substitution model describes the process from which a sequence of characters of a fixed size from some alphabet changes into another set of traits. For example, in cladistics, each position in the sequence might correspond to a property of a… …   Wikipedia

  • Substitution — For Wikipedia Template Substitution, see Substitution is the replacement of one thing with another. In mathematics: * Substitution rule, in calculus * Variable substitution, in first order logic * The substitution method of solving simultaneous… …   Wikipedia

  • Nonsynonymous substitution — A nonsynonymous substitution is a nucleotide mutation that alters the amino acid sequence of a protein. It is contrasted with synonymous substitutions which do not alter amino acid sequences. As nonsynonymous substitutions result in a biological… …   Wikipedia

  • Import substitution industrialization — (also called ISI) is a trade and economic policy based on the premise that a country should attempt to reduce its foreign dependency through the local production of industrialized products. Adopted in many Latin American countries from the 1930s… …   Wikipedia

  • несмысловая замена [нуклеотида] — synonymous substitution несмысловая замена [нуклеотида]. Замена нуклеотида в кодоне, не изменяющая его смысла, т.е. не приводящая к изменению последовательности аминокислот в соответствующей полипептидной цепи. (Источник: «Англо русский толковый… …   Молекулярная биология и генетика. Толковый словарь.

  • Ka/Ks ratio — In genetics, the Ka/Ks ratio (or ω, dN/dS), is the ratio of the rate of non synonymous substitutions (Ka) to the rate of synonymous substitutions (Ks), which can be used as an indicator of selective pressure acting on a protein coding gene.… …   Wikipedia

  • Models of DNA evolution — A number of different Markov models of DNA sequence evolution have been proposed. These substitution models differ in terms of the parameters used to describe the rates at which one nucleotide replaces another during evolution. These models are… …   Wikipedia

  • Neutral mutation — In genetics, a neutral mutation is a mutation that has no effect on fitness. In other words, it is neutral with respect to natural selection. For example, some mutations in a DNA triplet or codon do not change which amino acid is introduced: this …   Wikipedia

  • Natural selection — For other uses, see Natural Selection (disambiguation). Part of a series on Evolutionary Biology …   Wikipedia