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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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Heteroplasmic mitochondrial genome deletions. (A) Amplicons resulting from conventional PCRs with primers flanking the deletion area (primer positions shown in Figure 1) are shown for a subset of isolates analyzed (genomic DNAs were from bulk nematode extracts). Large bands represent intact mitochondrial genomes that contain the ψND5-2 element; small bands represent deletion-bearing genomes. Samples from the two Kenya clade isolates yielded only a single band of intermediate size due to the absence of ψND5-2 in their mitochondrial genomes. -C indicates the negative control (no genomic DNA) and M indicates the molecular marker (1 kb + DNA ladder from Invitrogen). (B) Estimated ND5 deletion frequencies (y axis) from 22 global superclade C. briggsae natural isolates based on qPCR data. TR indicates tropical-clade isolates and TE indicates temperate-clade isolates. Values shown in bar graph are means from four individual nematodes assayed per genotype – error bars show S. E. M.
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Figure 3: Heteroplasmic mitochondrial genome deletions. (A) Amplicons resulting from conventional PCRs with primers flanking the deletion area (primer positions shown in Figure 1) are shown for a subset of isolates analyzed (genomic DNAs were from bulk nematode extracts). Large bands represent intact mitochondrial genomes that contain the ψND5-2 element; small bands represent deletion-bearing genomes. Samples from the two Kenya clade isolates yielded only a single band of intermediate size due to the absence of ψND5-2 in their mitochondrial genomes. -C indicates the negative control (no genomic DNA) and M indicates the molecular marker (1 kb + DNA ladder from Invitrogen). (B) Estimated ND5 deletion frequencies (y axis) from 22 global superclade C. briggsae natural isolates based on qPCR data. TR indicates tropical-clade isolates and TE indicates temperate-clade isolates. Values shown in bar graph are means from four individual nematodes assayed per genotype – error bars show S. E. M.

Mentions: Upon further analyzing the ψND5-2 region in the C. briggsae natural isolates, we found that some strains harbor a large heteroplasmic mitochondrial genome deletion (871–887 bp, depending on isolate) that eliminated the 3' end of ψND5-2 and the 5' end (first 786 bp) of the ND5 protein-coding gene (Figure 1 and 3A). Directly repeated DNA sequence tracts in ND5 and the upstream ψND5-2 element flank the heteroplasmic ND5 deletion allele and are likely to play a causative role in promoting the deletions as direct repeats are also associated with heteroplasmic mitochondrial DNA deletions in C. elegans mutation-accumulations lines [6] and aging nematodes [29]. The observed deletion is expected to strongly and negatively affect ND5 protein-coding function as the deleted sequences encode more than 200 ND5 amino acids, 34 of which are conserved in C. elegans, Drosophila melanogaster and humans. The ψND5-2 region and associated heteroplasmic ND5 gene deletion was initially discovered in long PCR amplifications of C. briggsae natural isolate mitochondrial genome segments. The observation of the heteroplasmic deletion allele across multiple independent long PCR reactions (3 to 5 kb amplicons) that span many mtDNA genes provides strong evidence that the deletion is not a nuclear sequence of mitochondrial origin (numt), but rather a heteroplasmic mtDNA allelic variant. Furthermore, we have searched for the deletion-bearing sequences in the published C. briggsae nuclear genome sequence and found no evidence for the presence of a candidate numt. We also found no evidence for heteroplasmic deletions associated with ψND5-1.


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

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

Heteroplasmic mitochondrial genome deletions. (A) Amplicons resulting from conventional PCRs with primers flanking the deletion area (primer positions shown in Figure 1) are shown for a subset of isolates analyzed (genomic DNAs were from bulk nematode extracts). Large bands represent intact mitochondrial genomes that contain the ψND5-2 element; small bands represent deletion-bearing genomes. Samples from the two Kenya clade isolates yielded only a single band of intermediate size due to the absence of ψND5-2 in their mitochondrial genomes. -C indicates the negative control (no genomic DNA) and M indicates the molecular marker (1 kb + DNA ladder from Invitrogen). (B) Estimated ND5 deletion frequencies (y axis) from 22 global superclade C. briggsae natural isolates based on qPCR data. TR indicates tropical-clade isolates and TE indicates temperate-clade isolates. Values shown in bar graph are means from four individual nematodes assayed per genotype – error bars show S. E. M.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Heteroplasmic mitochondrial genome deletions. (A) Amplicons resulting from conventional PCRs with primers flanking the deletion area (primer positions shown in Figure 1) are shown for a subset of isolates analyzed (genomic DNAs were from bulk nematode extracts). Large bands represent intact mitochondrial genomes that contain the ψND5-2 element; small bands represent deletion-bearing genomes. Samples from the two Kenya clade isolates yielded only a single band of intermediate size due to the absence of ψND5-2 in their mitochondrial genomes. -C indicates the negative control (no genomic DNA) and M indicates the molecular marker (1 kb + DNA ladder from Invitrogen). (B) Estimated ND5 deletion frequencies (y axis) from 22 global superclade C. briggsae natural isolates based on qPCR data. TR indicates tropical-clade isolates and TE indicates temperate-clade isolates. Values shown in bar graph are means from four individual nematodes assayed per genotype – error bars show S. E. M.
Mentions: Upon further analyzing the ψND5-2 region in the C. briggsae natural isolates, we found that some strains harbor a large heteroplasmic mitochondrial genome deletion (871–887 bp, depending on isolate) that eliminated the 3' end of ψND5-2 and the 5' end (first 786 bp) of the ND5 protein-coding gene (Figure 1 and 3A). Directly repeated DNA sequence tracts in ND5 and the upstream ψND5-2 element flank the heteroplasmic ND5 deletion allele and are likely to play a causative role in promoting the deletions as direct repeats are also associated with heteroplasmic mitochondrial DNA deletions in C. elegans mutation-accumulations lines [6] and aging nematodes [29]. The observed deletion is expected to strongly and negatively affect ND5 protein-coding function as the deleted sequences encode more than 200 ND5 amino acids, 34 of which are conserved in C. elegans, Drosophila melanogaster and humans. The ψND5-2 region and associated heteroplasmic ND5 gene deletion was initially discovered in long PCR amplifications of C. briggsae natural isolate mitochondrial genome segments. The observation of the heteroplasmic deletion allele across multiple independent long PCR reactions (3 to 5 kb amplicons) that span many mtDNA genes provides strong evidence that the deletion is not a nuclear sequence of mitochondrial origin (numt), but rather a heteroplasmic mtDNA allelic variant. Furthermore, we have searched for the deletion-bearing sequences in the published C. briggsae nuclear genome sequence and found no evidence for the presence of a candidate numt. We also found no evidence for heteroplasmic deletions associated with ψND5-1.

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