Drift-barrier hypothesis and mutation-rate evolution

Abstract

Mutation dictates the tempo and mode of evolution, and like all traits, the mutation rate is subject to evolutionary modification. Here, we report refined 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 (N(e)), 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 N(e) 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 N(e).

Fig. 1.

(A) Relationship between the base-substitutional mutation rate/site/cell division and genome size. The regression includes all points except the four uppermost eukaryotes, for which the mutation-rate estimates are based on reporter constructs, log₁₀u = −8.663–1.096log₁₀G, where u is the mutation rate, and G is the genome size in megabases (r² = 0.872, df = 21). Points surrounded by a circle are based on mutation-accumulation experiments involving whole-genome sequencing; all others are based on reporter constructs. For euykaryotes: Cr, Chlamydomonas reinhardtii; Nc, Neurospora crassa; Pf, Plasmodium falciparum; Pt, Paramecium tetraurelia; Sc, Saccharomyces cerevisiae; Sp, Schizosaccharomyces pombe; Tb, Trypanosoma brucei. The prokaryote reported in this study, Mesoplasma florum, is denoted as Mf. The dashed regression line to the lower right includes multicellular eukaryotes (not shown) (4). (B) Relationship between the base-substitutional mutation rate/site/cell division and the effective population size (N_e) extrapolated from silent-site diversity. Eukaryotic regression (black): log₁₀u = −3.145–0.916log₁₀N_e (r² = 0.831); prokaryotic regression (blue): log₁₀u = −3.920–0.699log₁₀N_e (r² = 0.794). Labeled prokaryotic data points: Bs, Bacillus subtilis; Ec, Escherichia coli; Hp, Helicobacter pylori; Mt, Mycobacterium tuberculosis; Pa, Pseudomonas aeruginosa; Sa, Sulfolobus acidocaldarius (archaea); Se, Salmonella enterica; Tt, Thermus thermophila. (C) Relationship between genome-wide mutation rate/cell division for coding DNA and N_e. Regression: log₁₀(uG_e) = 3.109–0.757log₁₀N_e (r² = 0.844). The data for multicellular eukaryotes (red) are summarized in Tables S8, S9, and S10, which are slight updates from the data previously summarized (4).