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

Research output: Contribution to journalArticle

57 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)933-943
Number of pages11
JournalGenetics
Volume180
Issue number2
DOIs
StatePublished - Oct 1 2008
Externally publishedYes

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Population Genetics
Mutation Rate
Germ-Line Mutation
Alleles
Eukaryota
Cell Division
Theoretical Models
Costs and Cost Analysis
Mutation
Population
Neoplasms

ASJC Scopus subject areas

  • Genetics

Cite this

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

In: Genetics, Vol. 180, No. 2, 01.10.2008, p. 933-943.

Research output: Contribution to journalArticle

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