Transversion, inmolecular biology, refers to apoint mutation inDNA in which a single (two ring)purine (A orG) is changed for a (one ring)pyrimidine (T orC), or vice versa.[1] A transversion can be spontaneous, or it can be caused byionizing radiation oralkylating agents. It can only be reversed by a spontaneousreversion.
Although there are two possible transversions but only one possibletransition per base, transition mutations are more likely than transversions because substituting a single ring structure for another single ring structure is more likely than substituting a double ring for a single ring. Also, transitions are less likely to result in amino acid substitutions (due towobble base pair), and are therefore more likely to persist as "silent substitutions" in populations assingle nucleotide polymorphisms (SNPs).[2] A transversion usually has a more pronounced effect than a transition because the second and third nucleotidecodon position of theDNA, which to a large extent is responsible for thedegeneracy of thecode, is more tolerant of transition than a transversion: transitions are more likely to besynonymous substitutions than transversions, as one observes in thecodon table.
8-oxo-2'-deoxyguanosine (8-oxodG) is an oxidized derivative ofdeoxyguanosine, and is one of the major products ofDNA oxidation. DuringDNA replication in the germ line of mice, the oxidized base8-oxoguanine (8-oxoG) causes spontaneous and heritable G to T transversion mutations.[3] These mutations occur in different stages of thegerm cell lineage and are distributed throughout thechromosomes.
The location of a transversion mutation on a gene coding for a protein correlates with the extent of the mutation. If the mutation occurs at a site that is not involved with the shape of a protein or the structure of an enzyme or its active site, the mutation will not have a significant effect on the cell or the enzymatic activity of its proteins. If the mutation occurs at a site that changes the structure or function of a protein, therefore changing its enzymatic activity, the mutation can have significant effects on the survival of the cell.[4]
Of the natural nitrogenous bases of DNA, guanine is most prone to oxidation. Oxidation of guanine, also known as oxidative guanine damage, results in the formation of many products. These products trigger mutations, leading to DNA damage, and can pair with adenine and guanine through hydrogen bonding causing G-T transversions and G-C transversions, respectively.[5]
The mutation of theP53 gene is the most common gene mutation found in cancer cells. A study has shown that p53 mutations are common in tobacco-related cancers, with a variation in the amount of G-T transversions in lung cancer from smokers and non-smokers. In smokers’ lung cancer, the prevalence of G-T transversions is 30% compared to that of 12% in non-smokers. At many p53 mutational hotspots, a large number of the mutations are G-T events in lung cancers but almost exclusively G-A transitions in non-tobacco-related cancers.[6]
