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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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ψND5-2 compensatory mutations. (A) Phylogenetic distributions of three ψND5-2 direct repeat sequence haplotypes among temperate and tropical-clade C. briggsae isolates are shown on top. Black lines indicate lineages that encode DRSeq1 (identical to downstream ND5 sequence), blue lines show lineage with DRSeq2 and red lines show DRSeq3-encoding lineages. Boostrap support (neighbor-joining over maximum parsimony) is shown for relevant nodes. Specific DNA sequence changes in DRSeq2 and DRSeq3 are shown on bottom. (B) Variation in ND5 heteroplasmic deletion frequencies among isolates encoding different ψND5-2 sequences is shown. Error bars show S. E. M. (C) Mean fecundities of isolates encoding different ψND5-2 sequences are shown. Error bars show S. E. M.
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Figure 4: ψND5-2 compensatory mutations. (A) Phylogenetic distributions of three ψND5-2 direct repeat sequence haplotypes among temperate and tropical-clade C. briggsae isolates are shown on top. Black lines indicate lineages that encode DRSeq1 (identical to downstream ND5 sequence), blue lines show lineage with DRSeq2 and red lines show DRSeq3-encoding lineages. Boostrap support (neighbor-joining over maximum parsimony) is shown for relevant nodes. Specific DNA sequence changes in DRSeq2 and DRSeq3 are shown on bottom. (B) Variation in ND5 heteroplasmic deletion frequencies among isolates encoding different ψND5-2 sequences is shown. Error bars show S. E. M. (C) Mean fecundities of isolates encoding different ψND5-2 sequences are shown. Error bars show S. E. M.

Mentions: The heteroplasmic ND5 deletion observed in the C. briggsae natural isolates is flanked by directly repeated DNA sequence stretches in homologous regions of ψND5-2 and ND5 – one repeat copy remains in deletion-bearing genomes. We characterized patterns of sequence divergence at the 21 bp of directly repeated DNA sequence in the C. briggsae isolates and discovered the presence of three different haplotype sequences for the repeat unit present in ψND5-2 (Figure 4A); all isolates had identical sequences at the ND5 repeat unit. For the ψND5-2 repeat unit, the majority of isolates encoded an ancestral sequence (named DRSeq1 – see Figure 4A) that was identical to that present downstream in ND5. In the temperate clade, however, two divergent derived haplotype sequences were observed in the ψND5-2 direct repeat (DRSeq2 and DRSeq3), each containing two sequence differences relative to the downstream ND5 repeat, that are expected to render the isolates encoding these divergent sequences less susceptible to direct repeat-associated intragenomic deletion events as compared to the DRSeq1 repeat unit. Consistent with this expectation, isolates that encode DRSeq2 display significantly lower ND5 deletion proportions as compared to those that encode DRSeq1 (P < 0.05, two-tailed t-test) – see Figure 4B. Isolates encoding DRSeq3 also show lower ND5 deletion levels, though the difference as compared to those that encode DRSeq1 is not significant (P > 0.10, two-tailed t-test). When considered as groups, mean heteroplasmic deletion levels were higher in tropical-clade isolates (12.1%) as compared to temperate-clade isolates (7.3%), though the difference was not significant (P > 0.9, two-tailed t-test). We also analyzed fecundity variation with respect to the three sequence motifs and found that isolates encoding DRSeq2 displayed significantly elevated fecundity as compared to those encoding DRSeq1 (P < 0.001, two-tailed t-test) – see Figure 4C. Fecundities in isolates encoding DRSeq3 and DRSeq1, however, were highly similar and not significantly different (P > 0.1, two-tailed t-test). The relatively low ND5 deletion proportions and high fecundities associated with isolates encoding DRSeq2 are suggestive of compensatory mutation – in particular, the ψND5-2 substitutions are expected to result in reduced interactions of directly repeated sequences in ψND5-2 and ND5, thereby resulting in lower ND5 deletion incidences and higher fitness. However, we are again unable to account for the potential effects of nuclear loci.


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

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

ψND5-2 compensatory mutations. (A) Phylogenetic distributions of three ψND5-2 direct repeat sequence haplotypes among temperate and tropical-clade C. briggsae isolates are shown on top. Black lines indicate lineages that encode DRSeq1 (identical to downstream ND5 sequence), blue lines show lineage with DRSeq2 and red lines show DRSeq3-encoding lineages. Boostrap support (neighbor-joining over maximum parsimony) is shown for relevant nodes. Specific DNA sequence changes in DRSeq2 and DRSeq3 are shown on bottom. (B) Variation in ND5 heteroplasmic deletion frequencies among isolates encoding different ψND5-2 sequences is shown. Error bars show S. E. M. (C) Mean fecundities of isolates encoding different ψND5-2 sequences are shown. Error bars show S. E. M.
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Related In: Results  -  Collection

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Figure 4: ψND5-2 compensatory mutations. (A) Phylogenetic distributions of three ψND5-2 direct repeat sequence haplotypes among temperate and tropical-clade C. briggsae isolates are shown on top. Black lines indicate lineages that encode DRSeq1 (identical to downstream ND5 sequence), blue lines show lineage with DRSeq2 and red lines show DRSeq3-encoding lineages. Boostrap support (neighbor-joining over maximum parsimony) is shown for relevant nodes. Specific DNA sequence changes in DRSeq2 and DRSeq3 are shown on bottom. (B) Variation in ND5 heteroplasmic deletion frequencies among isolates encoding different ψND5-2 sequences is shown. Error bars show S. E. M. (C) Mean fecundities of isolates encoding different ψND5-2 sequences are shown. Error bars show S. E. M.
Mentions: The heteroplasmic ND5 deletion observed in the C. briggsae natural isolates is flanked by directly repeated DNA sequence stretches in homologous regions of ψND5-2 and ND5 – one repeat copy remains in deletion-bearing genomes. We characterized patterns of sequence divergence at the 21 bp of directly repeated DNA sequence in the C. briggsae isolates and discovered the presence of three different haplotype sequences for the repeat unit present in ψND5-2 (Figure 4A); all isolates had identical sequences at the ND5 repeat unit. For the ψND5-2 repeat unit, the majority of isolates encoded an ancestral sequence (named DRSeq1 – see Figure 4A) that was identical to that present downstream in ND5. In the temperate clade, however, two divergent derived haplotype sequences were observed in the ψND5-2 direct repeat (DRSeq2 and DRSeq3), each containing two sequence differences relative to the downstream ND5 repeat, that are expected to render the isolates encoding these divergent sequences less susceptible to direct repeat-associated intragenomic deletion events as compared to the DRSeq1 repeat unit. Consistent with this expectation, isolates that encode DRSeq2 display significantly lower ND5 deletion proportions as compared to those that encode DRSeq1 (P < 0.05, two-tailed t-test) – see Figure 4B. Isolates encoding DRSeq3 also show lower ND5 deletion levels, though the difference as compared to those that encode DRSeq1 is not significant (P > 0.10, two-tailed t-test). When considered as groups, mean heteroplasmic deletion levels were higher in tropical-clade isolates (12.1%) as compared to temperate-clade isolates (7.3%), though the difference was not significant (P > 0.9, two-tailed t-test). We also analyzed fecundity variation with respect to the three sequence motifs and found that isolates encoding DRSeq2 displayed significantly elevated fecundity as compared to those encoding DRSeq1 (P < 0.001, two-tailed t-test) – see Figure 4C. Fecundities in isolates encoding DRSeq3 and DRSeq1, however, were highly similar and not significantly different (P > 0.1, two-tailed t-test). The relatively low ND5 deletion proportions and high fecundities associated with isolates encoding DRSeq2 are suggestive of compensatory mutation – in particular, the ψND5-2 substitutions are expected to result in reduced interactions of directly repeated sequences in ψND5-2 and ND5, thereby resulting in lower ND5 deletion incidences and higher fitness. However, we are again unable to account for the potential effects of nuclear loci.

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