Mutational Biases

Abstract

Mutational biases refer to systematic asymmetries or nonuniformities in the occurrence of mutations, heritable changes that take place in an individual organism. Mutational biases arise by asymmetries in damage, repair and replication of the genetic material. Many such biases are known: familiar examples include transition:transversion bias, the CpG effect and deletion:insertion bias. Mutation biases are biologically significant to the extent that they modulate the probabilities of heritable diseases and of evolutionary changes.

Keywords: transition–transversion bias; GC bias; strand‐specific bias; insertion–deletion bias

Figure 1.

Nucleotide transversions (solid lines) and transitions (dashed lines) typically occur with different rates (A, adenine; G, guanine; C, cytosine; T, thymine).

Figure 2.

A bubble plot showing the relative rates of different types of DNA substitution mutations typical for mammalian genomes (based on results from Hwang and Green, ). The size of the bubble represents the relative rate of mutation of a nucleotide shown on the vertical axis to the nucleotide shown on the horizontal axis (asterisks, CpG context).

Figure 3.

While deamination of C results in uracil, recognized by repair enzymes as an error, deamination of 5‐methylcytosine results in T, which is not recognized as an error because it is normally present in DNA. In vertebrates, methylation of Cs occurs preferentially at sites followed by a G residue, leading to an unusual mutation pattern at CpG dinucleotides.

Figure 4.

Numbers of short insertion (plus symbols) or deletion (triangles) mutants in the Human Gene Mutation Database (Chuzhanova et al., ), shown on a double‐log scale. Given reasonable assumptions (most such indels are null alleles; the chance of ascertainment is not significantly affected by length), variation in frequencies of different types (insertion or deletion) and lengths of indels directly reflects differences in rates of mutation. Thus, deletion mutations occur at a rate about 4 times that of insertions (from the slopes of the regression lines). The rates fall off sharply with length, according to a power law (grey regression lines).

Figure 5.

Slipped‐strand mispairing (DNA polymerase slippage) causes insertions and deletions during replication of repetitive DNA.

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Schmegner C, Hoegel J, Vogel W and Assum G (2007) The rate, not the spectrum, of base pair substitutions changes at a GC‐content transition in the human NF1 gene region: implications for the evolution of the mammalian genome structure. Genetics 175(1): 421–428.

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How to Cite close
Yampolsky, Lev Y, and Stoltzfus, Arlin(Jul 2008) Mutational Biases. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001729.pub2]