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Genetics. 2008 Oct;180(2):933-43. doi: 10.1534/genetics.108.090456. Epub 2008 Aug 30.

The cellular, developmental and population-genetic determinants of mutation-rate evolution.

Author information

1
Department of Biology, Indiana University, Bloomington, Indiana 47405, USA. milynch@indiana.edu

Abstract

Although the matter has been subject to considerable theoretical study, there are numerous open questions regarding the mechanisms driving the mutation rate in various phylogenetic lineages. Most notably, empirical evidence indicates that mutation rates are elevated in multicellular species relative to unicellular eukaryotes and prokaryotes, even on a per-cell division basis, despite the need for the avoidance of somatic damage and the accumulation of germline mutations. Here it is suggested that multicellularity discourages selection against weak mutator alleles for reasons associated with both the cellular and the population-genetic environments, thereby magnifying the vulnerability to somatic mutations (cancer) and increasing the risk of extinction from the accumulation of germline mutations. Moreover, contrary to common belief, a cost of fidelity need not be invoked to explain the lower bound to observed mutation rates, which instead may simply be set by the inability of selection to advance very weakly advantageous antimutator alleles in finite populations.

PMID:
18757919
PMCID:
PMC2567392
DOI:
10.1534/genetics.108.090456
[Indexed for MEDLINE]
Free PMC Article

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