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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 element positions in C. briggsae mitochondrial genomes. Dashed boxes indicate the two ψND5 elements and open boxes indicate mtDNA genes. Protein-coding genes are indicated by their common abbreviations and tRNA genes are indicated by their respective associated single-letter amino acid codes. ψND5-1 is 214–223 bp, depending on isolate, and ψND5-2 is 325–344 bp. The dashed horizontal line on top indicates DNA sequences that are lost in heteroplasmic ND5 deletion variants and the arrows indicate the primer positions that are employed for conventional PCR assays.
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Figure 1: ψND5 element positions in C. briggsae mitochondrial genomes. Dashed boxes indicate the two ψND5 elements and open boxes indicate mtDNA genes. Protein-coding genes are indicated by their common abbreviations and tRNA genes are indicated by their respective associated single-letter amino acid codes. ψND5-1 is 214–223 bp, depending on isolate, and ψND5-2 is 325–344 bp. The dashed horizontal line on top indicates DNA sequences that are lost in heteroplasmic ND5 deletion variants and the arrows indicate the primer positions that are employed for conventional PCR assays.

Mentions: 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. The first ND5-like element (named ψND5-1) was identified between two tRNA genes, whereas the second larger element (ψND5-2) resides between the ND3 and ND5 protein-coding genes (Figure 1). ψND5-1 and ψND5-2 display 89.3% and 88.0% sequence identity, respectively, to homologous regions of the C. briggsae ND5 gene. There is 94.1% sequence identity between ψND5-1 and ψND5-2. We subjected the ψND5-1 and ψND5-2 sequences to conceptual translation using the appropriate genetic code in MEGA4 [23] to discover the presence of numerous internal stop codons, suggesting that these elements do not encode functional protein products. Whereas all 24 C. briggsae mtDNA sequences analyzed were found to harbor ψND5-1, only 22/24 isolates harbored ψND5-2 – this element was missing from the two Kenya isolate (ED3092, ED3101) mitochondrial genomes [24]. Although the mitochondrial genomes of C. elegans and C. remanei were found not to encode ψND5 elements, that of Caenorhabditis sp. n. 5 (isolate JU727), a recently-identified gonochoristic sister species to C. briggsae [25], was discovered to encode a divergent form of ψND5-1 (see Additional file 1).


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

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

ψND5 element positions in C. briggsae mitochondrial genomes. Dashed boxes indicate the two ψND5 elements and open boxes indicate mtDNA genes. Protein-coding genes are indicated by their common abbreviations and tRNA genes are indicated by their respective associated single-letter amino acid codes. ψND5-1 is 214–223 bp, depending on isolate, and ψND5-2 is 325–344 bp. The dashed horizontal line on top indicates DNA sequences that are lost in heteroplasmic ND5 deletion variants and the arrows indicate the primer positions that are employed for conventional PCR assays.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: ψND5 element positions in C. briggsae mitochondrial genomes. Dashed boxes indicate the two ψND5 elements and open boxes indicate mtDNA genes. Protein-coding genes are indicated by their common abbreviations and tRNA genes are indicated by their respective associated single-letter amino acid codes. ψND5-1 is 214–223 bp, depending on isolate, and ψND5-2 is 325–344 bp. The dashed horizontal line on top indicates DNA sequences that are lost in heteroplasmic ND5 deletion variants and the arrows indicate the primer positions that are employed for conventional PCR assays.
Mentions: 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. The first ND5-like element (named ψND5-1) was identified between two tRNA genes, whereas the second larger element (ψND5-2) resides between the ND3 and ND5 protein-coding genes (Figure 1). ψND5-1 and ψND5-2 display 89.3% and 88.0% sequence identity, respectively, to homologous regions of the C. briggsae ND5 gene. There is 94.1% sequence identity between ψND5-1 and ψND5-2. We subjected the ψND5-1 and ψND5-2 sequences to conceptual translation using the appropriate genetic code in MEGA4 [23] to discover the presence of numerous internal stop codons, suggesting that these elements do not encode functional protein products. Whereas all 24 C. briggsae mtDNA sequences analyzed were found to harbor ψND5-1, only 22/24 isolates harbored ψND5-2 – this element was missing from the two Kenya isolate (ED3092, ED3101) mitochondrial genomes [24]. Although the mitochondrial genomes of C. elegans and C. remanei were found not to encode ψND5 elements, that of Caenorhabditis sp. n. 5 (isolate JU727), a recently-identified gonochoristic sister species to C. briggsae [25], was discovered to encode a divergent form of ψND5-1 (see Additional file 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