Muller's Ratchet and compensatory mutation in Caenorhabditis briggsae mitochondrial genome evolution

Dana K Howe,Dee R Denver

doi:10.1186/1471-2148-8-62

Abstract

BackgroundThe theory of Muller' Ratchet predicts that small asexual populations are doomed to accumulate ever-increasing deleterious mutation loads as a consequence of the magnified power of genetic drift and mutation that accompanies small population size. Evidence for Muller's Ratchet and knowledge on its underlying molecular mechanisms, however, are lacking for natural populations.ResultsWe characterized mitochondrial genome evolutionary processes in Caenorhabditis briggsae natural isolates to show that numerous lineages experience a high incidence of nonsynonymous substitutions in protein-coding genes and accumulate unusual deleterious noncoding DNA stretches with associated heteroplasmic function-disrupting genome deletions. Isolate-specific deletion proportions correlated negatively with nematode fecundity, suggesting that these deletions might negatively affect C. briggsae fitness. However, putative compensatory mutations were also observed that are predicted to reduce heteroplasmy levels of deleterious deletions. Paradoxically, compensatory mutations were observed in one major intraspecific C. briggsae clade where population sizes are estimated to be very small (and selection is predicted to be relatively weak), but not in a second major clade where population size estimates are much larger and selection is expected to be more efficient.ConclusionThis study provides evidence that the mitochondrial genomes of animals evolving in nature are susceptible to Muller's Ratchet, suggests that context-dependent compensatory mutations can accumulate in small populations, and predicts that Muller's Ratchet can affect fundamental evolutionary forces such as the rate of mutation.

Highlights

The theory of Muller' Ratchet predicts that small asexual populations are doomed to accumulate ever-increasing deleterious mutation loads as a consequence of the magnified power of genetic drift and mutation that accompanies small population size
Noncoding DNA accumulation in Caenorhabditis mitochondrial genomes To search for natural mutational decay in C. briggsae, we analyzed nearly complete mitochondrial genome sequences (13,430/14,420 total bp) from 24 geographically diverse C. briggsae natural isolates (Table 1). mitochondrial DNA (mtDNA) sequences were amplified as four overlapping long PCR products (3–5 kb in size each) that were directly sequenced using a combination of PCR and internal sequencing primers
We discovered that most C. briggsae mitochondrial genomes harbor two presumed noncoding regions that are homologous to and likely derive from the NADH dehydrogenase 5 (ND5) protein-coding gene

Summary

Introduction

The theory of Muller' Ratchet predicts that small asexual populations are doomed to accumulate ever-increasing deleterious mutation loads as a consequence of the magnified power of genetic drift and mutation that accompanies small population size. Evidence for Muller's Ratchet and knowledge on its underlying molecular mechanisms, are lacking for natural populations. Evolutionary theory predicts that mutational decay is inevitable for small asexual populations, provided deleterious mutation rates are high enough Such populations are expected to experience the effects of Muller's Ratchet [1,2] where the most-fit class of individuals is lost at some rate due to chance alone, leaving the second-best class to suffer the same fate, and so on, leading to a gradual decline in mean fitness. The mutational meltdown theory [3,4] built upon Muller's Ratchet to predict a synergism between mutation and genetic drift in promoting the extinction of small asexual populations that are at the end of a long genomic decay process. Direct knowledge on the susceptibilities of natural populations to Muller's Ratchet and the molecular mechanisms underlying this process remain enigmatic

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Conclusion