Too Many Mutants with Multiple Mutations

ABSTRACT It has recently become clear that the classical notion of the random nature of mutation does not hold for the distribution of mutations among genes: most collections of mutants contain more isolates with two or more mutations than predicted by the mutant frequency on the assumption of a ran...

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Bibliographic Details
Published in:Critical reviews in biochemistry and molecular biology 2007-07, Vol.42 (4), p.247-258
Main Author: Drake, John W.
Format: Article
Language:English
Subjects:
Adaptation, Biological
Animals
Evolution, Molecular
Humans
hypermutation
Mutagenesis - genetics
Mutation - genetics
mutational clusters
Neoplasms - genetics
spontaneous mutation
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Summary:ABSTRACT It has recently become clear that the classical notion of the random nature of mutation does not hold for the distribution of mutations among genes: most collections of mutants contain more isolates with two or more mutations than predicted by the mutant frequency on the assumption of a random distribution of mutations. Excesses of multiples are seen in a wide range of organisms, including riboviruses, DNA viruses, prokaryotes, yeasts, and higher eukaryotic cell lines and tissues. In addition, such excesses are produced by DNA polymerases in vitro. These "multiples" appear to be generated by transient, localized hypermutation rather than by heritable mutator mutations. The components of multiples are sometimes scattered at random and sometimes display an excess of smaller distances between mutations. As yet, almost nothing is known about the mechanisms that generate multiples, but such mutations have the capacity to accelerate those evolutionary pathways that require multiple mutations where the individual mutations are neutral or deleterious. Examples that impinge on human health may include carcinogenesis and the adaptation of microbial pathogens as they move between individual hosts.
ISSN:1040-9238
1549-7798
DOI:10.1080/10409230701495631