- Synonymous substitution
A synonymous substitution (also called a "silent" substitution) is the evolutionary substitution of one base for another in an
exonof a genecoding 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 DNAbase 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 tRNAcan 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 ancestorof 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 mutationoccurs, 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 biasmay 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 methioninecodon that marks the beginning of the gene's open reading framemay 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 tumorcell.
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Look at other dictionaries:
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