The insect-killing bacterium Photorhabdus luminescens has the lowest mutation rate among bacteria

Jiao Pan,Way Sung,Hongan Long,Michael Lynch,Emily Williams

doi:10.1007/s42995-020-00060-0

Abstract

Mutation is a primary source of genetic variation that is used to power evolution. Many studies, however, have shown that most mutations are deleterious and, as a result, extremely low mutation rates might be beneficial for survival. Using a mutation accumulation experiment, an unbiased method for mutation study, we found an extremely low base-substitution mutation rate of 5.94 × 10–11 per nucleotide site per cell division (95% Poisson confidence intervals: 4.65 × 10–11, 7.48 × 10–11) and indel mutation rate of 8.25 × 10–12 per site per cell division (95% confidence intervals: 3.96 × 10–12, 1.52 × 10–11) in the bacterium Photorhabdus luminescens ATCC29999. The mutations are strongly A/T-biased with a mutation bias of 10.28 in the A/T direction. It has been hypothesized that the ability for selection to lower mutation rates is inversely proportional to the effective population size (drift-barrier hypothesis) and we found that the effective population size of this bacterium is significantly greater than most other bacteria. This finding further decreases the lower-bounds of bacterial mutation rates and provides evidence that extreme levels of replication fidelity can evolve within organisms that maintain large effective population sizes.

Highlights

Mutations are the ultimate source for genetic variation and contribute to diseases, cell senescence, and cancer (Alfred and Knudson 1971; Davies et al 2002)
Using a genome that we assembled de novo, we applied established methods of mutation analysis on 52 mutation accumulation (MA) lines of P. luminescens ATCC29999 (Lynch et al 2008) and identified 72 base-pair substitution mutations, yielding a base-substitution mutation rate of 5.94 × 10–11 per nucleotide site per cell division (95% Poisson confidence intervals = 4.65 × 10–11, 7.48 × 10–11), which is the lowest bacterial mutation rate to date (Table 1, Supplementary Files S1–S3)
In order to ensure that selection was limited in our MA experiment, we examined the distribution of mutations within non-coding and coding regions

Summary

Introduction

Mutations are the ultimate source for genetic variation and contribute to diseases, cell senescence, and cancer (Alfred and Knudson 1971; Davies et al 2002). Mutations provide the primary source for evolutionary processes, the mostly deleterious nature of mutations requires that the ability for selection to refine the mechanisms driving. Replication fidelity is limited by random genetic drift (Eyrewalker and Keightley 2007; Lynch et al 2016; Sung et al 2012a). In a typical MA experiment involving bacteria, numerous inbred or clonal lines are cultured on rich growth media and single-colonies are transferred repeatedly. This bottlenecking process reduces the effective population size (Ne, the population genetic parameter reflecting the size of an ideal population that meets all Hardy–Weinberg assumptions) and lessens the efficiency of selection, allowing all but the most deleterious mutations to drift to fixation (Bateman 1959; Mukai 1964). Using MA experiments, previous researchers have found that extremely low mutation rates exist both in unicellular eukaryotes

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Conclusion