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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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Summary of proposed molecular evolutionary causes and consequences of heteroplasmic ND5 deletions. The insertion of ψND5-2 (arrow 1) in the ancestor to the global C. briggsae clade (see Figure 2) is hypothesized to result in direct repeat-induced intragenomic recombination events (arrow 2) that in turn lead to heteroplasmic ND5 gene deletions (arrow 3). Expression of truncated ND5 gene products is hypothesized to promote elevated reactive oxygen species levels (arrow 4) that in turn promote higher mutation rates (arrow 5). Accumulation of substitutions (e.g. DRSeq2) in ψND5-2 direct repeats (arrow 2a) are hypothesized to cause reduced intragenomic recombination rates, thereby preventing the elevation of reactive oxygen species levels and associated mutation rate increases.
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Figure 6: Summary of proposed molecular evolutionary causes and consequences of heteroplasmic ND5 deletions. The insertion of ψND5-2 (arrow 1) in the ancestor to the global C. briggsae clade (see Figure 2) is hypothesized to result in direct repeat-induced intragenomic recombination events (arrow 2) that in turn lead to heteroplasmic ND5 gene deletions (arrow 3). Expression of truncated ND5 gene products is hypothesized to promote elevated reactive oxygen species levels (arrow 4) that in turn promote higher mutation rates (arrow 5). Accumulation of substitutions (e.g. DRSeq2) in ψND5-2 direct repeats (arrow 2a) are hypothesized to cause reduced intragenomic recombination rates, thereby preventing the elevation of reactive oxygen species levels and associated mutation rate increases.

Mentions: Comparative nematode mutation-accumulation studies show a significantly elevated deleterious genomic mutation rate in bottlenecked lines derived from C. briggsae versus C. elegans progenitors [18]. Furthermore, an elevated deleterious mutation rate was estimated for C. briggsae HK104-derived lines (encode DRSeq1) as compared to MA lines derived from the PB800 isolate that encodes DRSeq2, the candidate compensatory mutation that likely reduced ND5 deletion product levels [21]. The protein product encoded by the ND5 gene, predicted to be highly impaired in ND5 deletion-bearing genome products, is a central core subunit of Complex I of the mitochondrial electron transport chain [35]. Complex I-compromised organisms in well-studied animal systems- mammals, D. melanogaster, and C. elegans [36-38] – all produce elevated levels of mutagenic reactive oxygen species. Thus, we predict that C. briggsae ND5 deletion products are mutagenic, and that expression of truncated ND5 protein products results in elevated reactive oxygen species levels. One intriguing hypothesis for the mutational disparities observed between C. elegans and C. briggsae, and between HK104 and PB800 (note the close evolutionary relationships between these isolates in Figure 2), is that the elevated rates are due to increased mutagenic reactive oxygen species levels resulting from ND5 deletion products (Figure 6). This hypothesis also predicts that Muller's Ratchet can affect fundamental evolutionary parameters such as the mutation rate.


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

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

Summary of proposed molecular evolutionary causes and consequences of heteroplasmic ND5 deletions. The insertion of ψND5-2 (arrow 1) in the ancestor to the global C. briggsae clade (see Figure 2) is hypothesized to result in direct repeat-induced intragenomic recombination events (arrow 2) that in turn lead to heteroplasmic ND5 gene deletions (arrow 3). Expression of truncated ND5 gene products is hypothesized to promote elevated reactive oxygen species levels (arrow 4) that in turn promote higher mutation rates (arrow 5). Accumulation of substitutions (e.g. DRSeq2) in ψND5-2 direct repeats (arrow 2a) are hypothesized to cause reduced intragenomic recombination rates, thereby preventing the elevation of reactive oxygen species levels and associated mutation rate increases.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Summary of proposed molecular evolutionary causes and consequences of heteroplasmic ND5 deletions. The insertion of ψND5-2 (arrow 1) in the ancestor to the global C. briggsae clade (see Figure 2) is hypothesized to result in direct repeat-induced intragenomic recombination events (arrow 2) that in turn lead to heteroplasmic ND5 gene deletions (arrow 3). Expression of truncated ND5 gene products is hypothesized to promote elevated reactive oxygen species levels (arrow 4) that in turn promote higher mutation rates (arrow 5). Accumulation of substitutions (e.g. DRSeq2) in ψND5-2 direct repeats (arrow 2a) are hypothesized to cause reduced intragenomic recombination rates, thereby preventing the elevation of reactive oxygen species levels and associated mutation rate increases.
Mentions: Comparative nematode mutation-accumulation studies show a significantly elevated deleterious genomic mutation rate in bottlenecked lines derived from C. briggsae versus C. elegans progenitors [18]. Furthermore, an elevated deleterious mutation rate was estimated for C. briggsae HK104-derived lines (encode DRSeq1) as compared to MA lines derived from the PB800 isolate that encodes DRSeq2, the candidate compensatory mutation that likely reduced ND5 deletion product levels [21]. The protein product encoded by the ND5 gene, predicted to be highly impaired in ND5 deletion-bearing genome products, is a central core subunit of Complex I of the mitochondrial electron transport chain [35]. Complex I-compromised organisms in well-studied animal systems- mammals, D. melanogaster, and C. elegans [36-38] – all produce elevated levels of mutagenic reactive oxygen species. Thus, we predict that C. briggsae ND5 deletion products are mutagenic, and that expression of truncated ND5 protein products results in elevated reactive oxygen species levels. One intriguing hypothesis for the mutational disparities observed between C. elegans and C. briggsae, and between HK104 and PB800 (note the close evolutionary relationships between these isolates in Figure 2), is that the elevated rates are due to increased mutagenic reactive oxygen species levels resulting from ND5 deletion products (Figure 6). This hypothesis also predicts that Muller's Ratchet can affect fundamental evolutionary parameters such as the mutation rate.

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