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

Howe DK, Denver DR - BMC Evol. Biol. (2008)

Bottom Line: 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.This 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Zoology and Center for Genome Research and Biocomputing, Oregon State University, Corvallis, Oregon, 97331, USA. howed@science.oregonstate.edu

ABSTRACT

Background: 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, however, are lacking for natural populations.

Results: We 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.

Conclusion: This 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.

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πN/πS ratios for mtDNA protein-coding genes. The πN/πS ratios for ten mtDNA protein-coding genes were calculated for the temperate-clade (black bars, n = 11) and tropical-clade (white bars, n = 11) C. briggsae isolates. Ratios were not calculated for two mtDNA genes because no nonsynonymous substitutions were observed for ND4L and COII in the temperate and tropical isolates, respectively. Concatenated protein-coding gene data files (12 genes) were also analyzed in the temperate and tropical-clade isolates, as well as in a set of C. elegans (dashed bar, n = 17) isolates.
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Figure 5: πN/πS ratios for mtDNA protein-coding genes. The πN/πS ratios for ten mtDNA protein-coding genes were calculated for the temperate-clade (black bars, n = 11) and tropical-clade (white bars, n = 11) C. briggsae isolates. Ratios were not calculated for two mtDNA genes because no nonsynonymous substitutions were observed for ND4L and COII in the temperate and tropical isolates, respectively. Concatenated protein-coding gene data files (12 genes) were also analyzed in the temperate and tropical-clade isolates, as well as in a set of C. elegans (dashed bar, n = 17) isolates.

Mentions: We found that the πN/πS ratio was greater in the temperate-clade isolates as compared to the tropical-clade isolates for 8/10 genes (Figure 5). For the concatenated gene datasets, the πN/πS ratio was higher in the temperate-clade C. briggsae isolates than that of the tropical-clade C. briggsae and C. elegans datasets. We attempted to apply meaningful confidence intervals on the πN and πS estimates using coalescent simulations in DnaSP, however the small numbers of compared sequences (n = 11 for each of the temperate and tropical datasets) and low levels of nucleotide diversity (see Additional file 3) precluded our ability to do so. Nonetheless, we observed dramatic magnitudinal differences in πN/πS ratios between the temperate- and tropical-clade C. briggsae isolates that suggest an increased susceptibility of temperate isolates to the accumulation of nonsynonymous substitutions. The πN/πS ratio was remarkably high for ND3 in the temperate isolates, being nearly equal to one. These observations suggest that C. briggsae temperate isolates are particularly susceptible to the accumulation of deleterious mutations throughout the mitochondrial genome, consistent with expectations based on low Ne in this intraspecific clade. The specific fitness effects of these nonsynonymous substitutions, however, remain enigmatic and it is possible that some fraction of them (particularly those encoding NADH dehydrogenase complex subunits) might be advantageous in the context of the heteroplasmic ND5 deletion products.


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

Howe DK, Denver DR - BMC Evol. Biol. (2008)

πN/πS ratios for mtDNA protein-coding genes. The πN/πS ratios for ten mtDNA protein-coding genes were calculated for the temperate-clade (black bars, n = 11) and tropical-clade (white bars, n = 11) C. briggsae isolates. Ratios were not calculated for two mtDNA genes because no nonsynonymous substitutions were observed for ND4L and COII in the temperate and tropical isolates, respectively. Concatenated protein-coding gene data files (12 genes) were also analyzed in the temperate and tropical-clade isolates, as well as in a set of C. elegans (dashed bar, n = 17) isolates.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2279117&req=5

Figure 5: πN/πS ratios for mtDNA protein-coding genes. The πN/πS ratios for ten mtDNA protein-coding genes were calculated for the temperate-clade (black bars, n = 11) and tropical-clade (white bars, n = 11) C. briggsae isolates. Ratios were not calculated for two mtDNA genes because no nonsynonymous substitutions were observed for ND4L and COII in the temperate and tropical isolates, respectively. Concatenated protein-coding gene data files (12 genes) were also analyzed in the temperate and tropical-clade isolates, as well as in a set of C. elegans (dashed bar, n = 17) isolates.
Mentions: We found that the πN/πS ratio was greater in the temperate-clade isolates as compared to the tropical-clade isolates for 8/10 genes (Figure 5). For the concatenated gene datasets, the πN/πS ratio was higher in the temperate-clade C. briggsae isolates than that of the tropical-clade C. briggsae and C. elegans datasets. We attempted to apply meaningful confidence intervals on the πN and πS estimates using coalescent simulations in DnaSP, however the small numbers of compared sequences (n = 11 for each of the temperate and tropical datasets) and low levels of nucleotide diversity (see Additional file 3) precluded our ability to do so. Nonetheless, we observed dramatic magnitudinal differences in πN/πS ratios between the temperate- and tropical-clade C. briggsae isolates that suggest an increased susceptibility of temperate isolates to the accumulation of nonsynonymous substitutions. The πN/πS ratio was remarkably high for ND3 in the temperate isolates, being nearly equal to one. These observations suggest that C. briggsae temperate isolates are particularly susceptible to the accumulation of deleterious mutations throughout the mitochondrial genome, consistent with expectations based on low Ne in this intraspecific clade. The specific fitness effects of these nonsynonymous substitutions, however, remain enigmatic and it is possible that some fraction of them (particularly those encoding NADH dehydrogenase complex subunits) might be advantageous in the context of the heteroplasmic ND5 deletion products.

Bottom Line: 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.This 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Zoology and Center for Genome Research and Biocomputing, Oregon State University, Corvallis, Oregon, 97331, USA. howed@science.oregonstate.edu

ABSTRACT

Background: 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, however, are lacking for natural populations.

Results: We 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.

Conclusion: This 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.

Show MeSH
Related in: MedlinePlus