Drift-barrier hypothesis and mutation-rate evolution

Way Sung, Matthew S. Ackerman, Samuel F. Miller, Thomas G. Doak, Michael Lynch

Research output: Contribution to journalArticlepeer-review

259 Scopus citations


Mutation dictates the tempo and mode of evolution, and like all traits, the mutation rate is subject to evolutionary modification. Here, we report re fined estimates of the mutation rate for a prokaryote with an exceptionally small genome and for a unicellular eukaryote with a large genome. Combined with prior results, these estimates provide the basis for a potentially unifying explanation for the wide range in mutation rates that exists among organisms. Natural selection appears to reduce the mutation rate of a species to a level that scales negatively with both the effective population size (Ne), which imposes a drift barrier to the evolution of molecular refinements, and the genomic content of coding DNA, which is proportional to the target size for deleterious mutations. As a consequence of an expansion in genome size, some microbial eukaryotes with large Ne appear to have evolved mutation rates that are lower than those known to occur in prokaryotes, but multicellular eukaryotes have experienced elevations in the genome-wide deleterious mutation rate because of substantial reductions in Ne.

Original languageEnglish (US)
Pages (from-to)18488-18492
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number45
StatePublished - Nov 6 2012
Externally publishedYes


  • Random genetic drift
  • Replication fidelity

ASJC Scopus subject areas

  • General


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