Transcriptional errors and the drift barrier.

Population genetics predicts that the balance between natural selection and genetic drift is determined by the population size. Species with large population sizes are predicted to have properties governed mainly by selective forces; whereas species with small population sizes should exhibit features governed by mutational processes alone. This “drift-barrier hypothesis” has been successful in explaining extensive variation in genome size, mutation rate, transposable element abundance, and other molecular features across diverse taxa (1–3). However, in PNAS Traverse and Ochman (4) report a striking exception to this theory by showing that transcriptional error rates are nearly equal across several bacterial species with very different population sizes. Although the term “drift barrier” was coined in the context of mutation rates (5), the drift-barrier hypothesis applies to any heritable trait (e.g., ref. 6), and so it can provide a simple explanation for patterns of many molecular traits across the diversity of life. The explanation relies on the fact that mutations whose effects on fitness are smaller than the inverse of the population size behave like neutral mutations. As a result, natural selection will tend to optimize a trait until the selective benefits of further optimization are smaller than the inverse of the population size (7): that is, until the population hits the drift barrier. Because the location of the drift barrier depends on the population size, so too should the values of these phenotypic traits. Thus, differences in population size among species can explain a concerted syndrome of traits at the cellular and molecular levels (1–3, 5, 6). In the context of broad empirical support for the drift-barrier hypothesis, the results of Traverse and Ochman (4) are particularly surprising. Using a CircSeq (8) strategy (based on the sequencing of short, circularized fragments of mRNA that are copied multiple times by rolling-circle amplification before sequencing) to reduce errors in high-throughput sequencing, Traverse and Ochman measured transcriptional error rates in Escherichia coli along with two endosymbiotic prokaryotes, Buchnera aphidicola and Carsonella ruddii. These endosymbionts feature dramatically reduced genome sizes, increased mutation rates, and other features typical of their small population sizes, including the loss of several transcriptional fidelity factors (4). Nevertheless, Traverse and Ochman report less than twofold variation in the rates of transcriptional errors among these three species. This result is in sharp contrast to mutation rates, which differ by orders of magnitude between species (5).